Anatomy

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    The Size of Anterior Fontanel in Neonates and Infants in Addis Ababa
    (2004-07) G/Meskel, Tarekegn; Kinfu, Yamrot (PhD)
    The size and the time of closure of anterior fontanel (AF) is often used in the diagnosis of disorders like altered skeletal morphogenesis, increased intracranial pressure, hormonal disorders and others. In order to properly utilize AF size in the diagnosis of different disorders, it is necessary to establish a normal range of AF sizes related to age. Racial differences in the size of AF and its time of closure has been reported and there are many countries with their own national standard. To my knowledge, there is no study done to determine the AF size and its time of closure in Ethiopian neonates and infants. The present study aims to establish mean AF size for Addis Ababa (A.A.) neonates and infants at the ages of 3, 46, 76, 106 and 270 days. The study is a cross sectional design carried out from January 2003 to December 2003 in A.A. and the study sites chosen were Tikur Anebessa Specialized Hospital, Zewditu Memorial Hospital, Tekele Haymanot and Wereda 23 Health Centers. The subjects were 687 neonates and infants, of which 363 were males and 324 were females. All cases fulfilling the inclusion criteria were included in a row until the targeted sample size was attained. The AF size, body weight, body length and head circumference were measured. When measuring AF size, first the four vertices were identified. After marking the vertices with washable ink, the marks were transferred on a sheet of paper. From the marks transferred on the sheet of paper, the anterior-posterior and the lateral dimensions were measured. The mean of the anterior-posterior and the lateral dimensions was taken as AF size. The mean AF size progressively decreased with age except at 106 days measurement which showed increase over the 76 days measurement. In all ages considered, no significant difference (p>0.05) was found in neonates and infants of different gender, birth order, gestational age and economic status. AF closure was observed beginning at the age of 76 days (0.8%) and the percent of closure increased with age. In Infants at the age of 270 days, 39.6% of them had closed AF. There were no significant (p>0.05) correlations between AF size and body weight, body length and head circumference while there was negative significant (p<0.05) correlation between AF size and age. The result of the present study shows congruence with the study on Nigerian and Indian neonates but disagrees with the study done on Arab, Israeli, China and white neonates and infants. Further study in different parts of Ethiopia is recommended to establish a national age- related standard for AF size and its time of closure. Key words: Anterior fontanel, Anterior-posterior dimension, lateral dimension, Neonate and infant
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    Effect of Ethanol and Khat (Catha Edulis Forsk)on Cerebellar Cortex of the Rat
    (Addis Abeba University, 2004-12) Muche, Abebe; Makonnen, Eyasu (Professor)
    This experimental study included three age groups of rats: post natal day (PND) 6, 13 and 30. Each group contained control, ethanol treated (ET), khat treated (KT) and combination of khat and ethanol treated (CT) categories. They were treated with vehicle, ethanol and khat, respectively for 30 days using blunt needle. At the end of experiment, all the animals were scarified, their brain was dissected out and immersion fixed. The brain and cerebellum were separately weighed, and cerebellum was processed for routine histology and sectioned. The serially sectioned tissues of cerebellum was stained with toluidine blue and observed using light microscope. In the rats of all age groups, the body weight increment at the end of experimental period was significantly less in the treated ones than their respective controls at P< 0.01. Between the treated rats, this was less for the ET rats than the KT rats, although not statistically significant (P>0.05). Similarly, the weight of the brain as a whole and cerebellar weight, part of brain, of the treated rats were significantly less than their respective controls (P<0.01). These weights were also less for the ET rats than for the KT rats, though not statistically significant. In the rats of PND 6 group, the following results were found: The volume of cerebellar cortex as well as the total number of Purkinje neurons of the ET rats were significantly less than the controls and KT rats at P<0.01 and P<0.05, respectively. However, no statistically significant difference was observed between the controls and KT rats. The numerical density and volume fractionof Purkinje neurons of ET rats was found to be significantly greater than those of control or KT rats (P<0.05). In addition, the numerical density and volume fraction of Purkinje neurons were greater in the KT rats than their corresponding controls, but no Xi statistically significant difference was observed. The mean diameter of Purkinje neurons was significantly less in the ET rats than in KT rats which in turn was significantly less than the control rats (P<0.01).In the rats of PND 13 and 30, the patterns of the results of all the different parameters investigated consistently followed those of the rats of PND 6 as summarized above, However, the values were found to be statistically non- significant. In addition, the results of all the parameters for the CT rats of PND 30 rats showed values in between KT and ET rats, though these were also statistically non- significant. However, CT rats of PND 6 and 13 died after two days of treatment. In conclusion, the study depicted that PND 6 is an extremely vulnerable period during which the rat cerebellar Purkinje neurons are particularly susceptible to the effect of high dose of ethanol. However, a similar level and duration of ethanol exposure commencing during PND 13 and 30 has no significant effect on the volume of cerebellar cortex, numerical density of Purkinje neurons, total number of Purkinje neurons and volume fraction of Purkinje neurons. Treatment of khat and combination of khat and ethanol is lethal at an early age, however it does not significantly change the above mentioned parameters at the latter ages (PND 30) Key words: Cerebellar cortex, Purkinje neurons, Stereology, Khat, Ethanol, Post natal day
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    The Toxic Effects of Vernonia Bipontini on Some Blood Parameters and on Liver and Kidney Tissues
    (Addis Abeba University, 2009-05) Alebachew, Mebratu; Makonnen, Eyasu (Professer)
    Toxicological studies are sources of useful information for evaluating the therapeutic benefits of locally used medicinal plants. Vernonia bipontini (V. bipontini) is a herb used for treatment of malaria and malaria related symptoms in Ethiopia. However, its side effects have not been studied. In this study, the toxic effects of aqueous and methanolic extracts of V. bipontini leaves on some blood parameters and on liver and kidney, tissues in mice were investigated. Lethal doses at which 50% of experimental mice died (LD50s) in both aqueous and methanolic leaf extracts of V. bipontini were determined by administering different doses (1250-3250mg/kg for aqueous leaf extract and 1250-2750mg/kg for methanolic leaf extract) to experimental animals using intragastric catheter. For long-term toxicity study, sixty male and female Swiss albino mice were equally divided into six groups of 10 animals each. Groups1 and 2 were set as the control and received 0.5ml of distilled water and 0.5ml of 4% tween in distilled water, respectively, at 24 hrs intervals for 45 days. Group 3 and 4 were subjected to oral administration of the aqueous leaf extract at 400 and 800mg/kg, respectively, while group 5 and 6 were treated at 400 and 800mg/kg of methanolic leaf extract, respectively in 24 hrs intervals for 45 days. All groups were closely observed for any physical and behavioral alterations. Body weights of the mice were recorded on the first day and the last day of administration. Each animal was sacrified under diethyl ether anesthesia on the 46th day. Following sacrifice, blood sample was collected by cardiac puncture using sterile needle and 5ml syringe into heparinized test tubes for hematological studies and into non-heparinized tubes for biochemical analysis. Hematological parameters (total RBC, WBC, platelets, lymphocytes, Hgb, Hct, Mcv, Mch, and Mchc) and biochemical parameters (AST, ALT, ALP, and urea) were evaluated. Through a vertical, midline incision, the liver and kidney of each animal were removed and cleaned of the surrounding tissues. Each sample was fixed in 10% buffered formalin overnight. The tissues were processed for light microscopy. The LD50s of the aqueous and methanolic leaf extracts of V. bipontini were 2500.62±5.24 mg/kg and 2130.6±1.5mg/kg, respectively. No deaths were recorded among the control groups. The aqueous leaf extract has no significant (P>0.05) effect on liver and kidney weights, and hematological and biochemical parameters at all doses when compared with control group. Treatment with 800mg/kg body weight of methanolic leaf extract significantly (P<0.05) decreased body, liver and kidney weights, RBC, Hgb, Mch, Mchc, platelets and significantly increased serum AST, ALT and ALP levels while 400mg/kg dose had no effect on these parameters. The reduced organ weights did not correlate with loss of body weight at 800mg/kg bw of methanolic leaf extract of the plant. Light microscope observations of liver tissue of mice treated with 800mg/kg of the methanolic leaf extract revealed dilated sinusoids, nuclear enlargement, bi-nucleation of hepatocytes, peripheral cramped chromatin, shrinkages (single cell death) of hepatocytes, fragmentation of hepatocytes (apoptosis) while no histopathological changes were observed in liver and kidney of mice treated at 400mg/kg of the methanolic leaf extract and at all doses of aqueous leaf extract. Kidney tissue sections of mice did not show significant histopathological changes at 400mg/kg of the same methanolic leaf extract of V. bipontini. However, at 800mg/kg kidney sections showed that increase cellularity of glomerulus and urinary space obliteration. In conclusion, this study suggests that the aqueous leaf extract of this plant may be safe, even when taken for 45 days at higher dose (800mg/kg). This is in agreement with traditional claim of the water preparation of V. bipontini leaves. However, methanolic leaf extract may be phytotoxic to liver that resulted in a rise in serum AST, ALT and ALP levels after 45 days herbal administration at high dose. Further studies would be needed to identify the active ingredients responsible for such toxicities. Key words: V. bipontini, Swiss albino mice, Liver, Kidney, Hematological and Biochemical parameters
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    The Effects of Chronic Treatment with DODONAEA ANGUSTIFOLIA Seed Extracts on some Hematological and Biochemical Composition of Blood and Histopathology of Liver and Kidney in Mice.
    (Addis Abeba University, 2010-06) Geneti, Soressa Abebe; Dr.Kinfu, Yamrot; Makonnen, Eyasu(Prof.); Dr.Ergete, Wondwossen; Urga, Kelbessa
    In Ethiopia many medicinal plants are used for the treatment of malaria including Dodonaea angustifolia seed with out considering their side effects. Therefore, the present study attempts to evaluate the chronic effect of crude extracts of D. angustifolia seeds on some hematological and biochemical parameters and histopathology of liver and kidney of mice. For the chronic treatment, animals were administered with the crude extracts of the plant through the oral route using oral gavage for six weeks at doses of 400 mg/kg/bw and 800 mg/kg/bw of the aqueous extract and 400 mg/kg/bw and 600 mg/kg of the methanolic extract. At the end of the experiment, all mice under treatment were sacrificed after blood collection for hematological and biochemical analysis and liver and kidney sections were randomly taken for tissue processing. The results of hematological and biochemical analysis as well as the microscopic examinations of the liver and kidney sections were compared with control groups. The hematological and biochemical results showed no statistically significant differences between the aqueous extract treated mice at both doses of 400 mg/kg/bw and 800 mg/kg/bw and the control group. In contrast, statistically significant elevation in ALT, AST, urea and creatinine were observed in methanolic extract treated mice at a dose of 600 mg/kg/bw as compared to the control group. Histopathological examinations of the liver and kidney sections of aqueous crude extract treated mice at both doses of 400 mg/kg/bw and 800 mg/kg/bw showed similar histological appearance as that of the control group except some focal inflammation were observed around central vein at dose of 800 mg/kg/bw of the aqueous extract of the plant. In contrast, significant histopathological changes were observed in liver and kidney sections of methanolic crude extract treated mice at dose of 600 mg/kg/bw with focal cellular infiltration around central vein of the liver sections at 400 mg/kg/bw showing the dose dependent effect of methanolic crude extract of the plant. In conclusion, the aqueous crude extract is safe to use at effective dose of 400 mg/kg/bw whereas the methanolic crude extract of D. angustifolia at the same effective dose (400 mg/kg/bw) as that of aqueous crude extract has slight toxic effect but adversely affects the biochemical parameter and histology of liver and kidney as the dose level increases to 600 mg/kg/bw. As the aqueous extract did not show adversity at the effective dose, it is recommended that medicinal plant users choose the aqueous extract of the plant. Further investigation is also recommended to isolate metabolites that may contribute the toxic effect of methanolic crude extract on liver and kidney.
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    Project Paper on Risk of Birth Defects Associated with in Utero Exposure to Antiretroviral Drugs
    (Addis Ababa University, 2013-02) Taye, Amsalu; Dr. Afework, Mekbeb (PhD)
    Antiretroviral compounds differ from most other new pharmaceutical agents in that they havebecome widely prescribed in pregnancy in the absence of proof of safety. In this paperantiretroviralagents used in pregnant women infected with humanimmunodeficiency virus and their effects on theinfantsare reviewed.This review gives an overview aboutinvivoandinvitrodevelopmental toxicityand teratogenicity of the anti-AIDS drugs (antiretrovirals),inexperimental animalsandhumans. Animal embryos exposed in vivo to antiretrovirals exhibited significantly increased pregnancylosses, drugs incorporation into the DNA of fetal organs, external abnormalities, skeletal defects,developmental toxicity, carcinogenicity, reduced weight, anemia, deaths and significantmitochondrial damage. The invitroantiretrovirals exposure of animal cells or organs resulted incytotoxicity, growth retardation, chromosomal aberrations, mutations, sister chromatid exchange andother genotoxic effects. Inearlier human studies, management of AIDS positive pregnant womenwith antiretrovirals revealed exposure of their infants to such drugs with evidence of adverse events.However, recent publications present conflicting data about the associations between antiretroviralsand adverse pregnancy outcomes. Because of the increasingly frequent use of highly active antiretroviral therapy during pregnancy,ongoing efforts are needed to monitor any long-term effects of in uteroexposure to themultipleantiretroviral agentsused.
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    Project paper on risk of Birth Defects associated with in utero exposure to Antiretroviral Drugs
    (Addis abeba, 2013-04-01) AMSALU TAYE; MEKBEB AFEWORK
    associated with in utero exposure to Antiretroviral Drugs
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    Effects of Maternal Folic Acid Supplementation on the Development of Neural Tube and Cardiovascular System of the off springs in Human and Animal Models
    (Addis Abeba University, 2014-06) Meskelu, Mekonin; Gebru, Girmai (PhD)
    Folate is a water-soluble vitamin B present in legumes (e.g. beans, peas and lentils), leafy green vegetables (e.g. spinach and asparagus), liver and certain fruits (e.g. banana, cantaloupe and strawberry). Folic acid supplementation to pregnant women had no acute and long-term adverse effects on the health status of mothers as well as the new born infants. Maternal folic acid supplementation had no significant association with multiple births. Maternal folic acid supplementation had a protective effect for neural tube defects (NTDs) especially spina bifida and anencephaly. Concomitant administration of maternal folic acid and methionine may also prevent retinoic acid induced cleft palate than use of folic acid alone. Maternal obesity before pregnancy with body mass index (BMI) ≥30 kg/m2 was significantly associated with an approximately two fold increased risk of NTDs in offspring. The NTD protective association of folic acid was also stronger in overweight/ obese women BMI ≥ 25 kg/m2 than in normal/underweight women BMI < 25 kg/m2. Food fortification with folic or maternal supplementation of folic acid may have a protective effect for coarctation of aorta and left ventricular outflow tract obstruction, but no significant association was observed for tetralogy of Fallot and d-transposition of the great arteries. High doses of daily maternal folate supplementation (50 mg/kg/day) during embryonic/fetal development are necessary for early post-implantation embryonic viability, chorioallantoic fusion, hematopoiesis, and the development of neural tube and heart. Maternal supplementation of multivitamin containing folic acid had more effective in preventing NTDs and congenital heart defects (CHDs) than use of folic acid alone, if it starts two months before conception and continues until completion of the second month of pregnancy and the frequency should be higher than five times per week. Use of vegetable and fruit during pregnancy also has a beneficial effect in preventing NTDs. Despite the protective effect of folic acid in NTDs by facilitating the neural tube closure, additional investigation is required to understand the exact mechanism of action of folic acid in neural tube. Key words: folic acid; maternal; supplementation; NTDs; CHDs
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    The Histological Effect of Alcohol on the Liver and kidney of Animals
    (Addis Abeba University, 2014-06) Abrha, Nigus; Seyoum, Girma (PhD)
    Alcohol consumption represents the third largest risk factor for disease burden in most countries of the world. Alcohol can damage nearly every organ and system in the body such as liver and kidney. Alcohol is eliminated from the body by various metabolic mechanisms. The primary enzymes involved in these metabolic mechanisms are aldehyde dehydrogenase (ALDH), alcohol dehydrogenase (ADH), cytochrome P450 (CYP2E1), and catalase. Variations in the genes for these enzymes have been found to influence alcohol consumption, alcohol-related tissue damage, and alcohol dependence. The consequences of alcohol metabolism include oxygen deficits (i.e., hypoxia) in the liver; interaction between alcohol metabolism by products and other cell components, resulting in the formation of harmful compounds (i.e., adducts); formation of highly reactive oxygen-containing molecules (i.e., reactive oxygen species) that can damage other cell components; tissue damage; fetal damage; cancer; and medication interactions. The effects of alcohol on various tissues depend on its concentration in the blood i.e. blood alcohol concentration over time. Blood alcohol concentration (BAC) is determined by how quickly alcohol is absorbed, distributed, metabolized, and excreted. BAC is influenced by the rate of alcohol drinking, the presence of food in the stomach, and the type of alcoholic beverage, variations in the principal alcohol- metabolizing enzymes namely alcohol dehydrogenase and aldehyde dehydrogenase. Alcohol readily diffuses across membranes and distributes through all cells and tissues, and at these concentrations, it can acutely affect cell function by interacting with certain proteins and cell membranes. Alcohol metabolism also results in the generation of acetaldehyde that may contribute to tissue damage, the formation of damaging molecules known as ROS, and a change in the redox state of liver cells. Understanding the balance of alcohol’s removal and the accumulation of potentially damaging metabolic byproducts, as well as how alcohol metabolism affects other metabolic pathways, is essential for appreciating both the short- term and long-term effects of the body’s response to alcohol intake (Zakhari, 2006). Key word: Alcohol, Liver, Kidney, Necrosis and Degenerative change
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    The Effect of Melatonin in the Testes and Ovaries of Animal Models
    (Addis Abeba University, 2014-07) Assefa, Hafte; Gebru, Girmai (PhD)
    Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone synthesized and secreted primarily by the pineal gland during the dark hours at night. Other tissues and cells are also involved in its synthesis in the retina, gastrointestinal tract, lymphocytes and the skin. There has been increasing evidence that extrinsic doses of melatonin cause certain pharmaceutical, biochemical and physiological effects on the mammalian genital organs (such as in the testes and ovaries). It has an inhibitive effect on hypothalamus-hypophysis-gonads system. Furthermore, it increases the secretion of opioid peptides, which in turn decrease the secretion of gonadotropin-releasing hormone (GnRH). This project paper is designed to review and discuss scientific research articles regarding the effect of melatonin on the testes and ovaries of animal models. For these purpose different animal models, different time of exposure and different doses of melatonin administration was employed. As a result, the experimental animals treated with melatonin displayed inhibited spermatogenesis, tubular degeneration and necrosis, obstruction in tubular lumen and lymphocytic infiltration. In addition, melatonin administration caused marked reductions in absolute and relative testicular weight, size, serum testosterone concentration, atretic follicles and sperm of experimental animals. Though there was no difference in ovarian volume and relative ovarian weights, a differential count of various follicles has revealed significantly higher number of primordial, primary, secondary and antral follicles in melatonin treated rats. In the 90-day-old ovary, there was almost double the number of corpora lutea between control and melatonin programmed rats. Moreover, the histological effect of the testicular and ovarian damage increased with increased dosage of melatonin administration and with increased days after exposure to different doses of melatonin. Keywords: Antral follicles, Atretic follicles, Corpora lutea, Melatonin, Ovaries, spermatogenesis, Testes.
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    The Effect of Solanum nigrum L. on Histopathology of Liver and Kidneys of Rats
    (Addis Abeba University, 2014-07) Teklehaimanot, Hadgu; Gebru, Girmai (PhD)
    Solanum nigrum L. is commonly called black nightshade that belongs to Solanaceae (potato) family. It is a fairly common herb or short-lived perennial shrub, found in many wooded areas, as well as disturbed habitats. Various experimental based scientific studies were conducted in order to investigate the efficacy and safety of S. nigrum extract. It was shown that this plant has various bioactive ingredients such as alkaloids, solanins, saponins, flavonoids, tannins, steroidal glycoalkaloids, steroidal genin and vitamins. These constituents are responsible for diverse activities including anti-inflammatory, anti-bacterial, anti-diabetic, anti-fungal, anti-oxidant, hepatoprotective, nephroprotective and cytoprotective effects. In addition, these bioactive constituents have free radical scavenging capacity and anti-lipid peroxidation activities by stabilization of plasma membranes as well as repair of liver and kidney tissue damage. Moreover, the result of this review showed that S. nigrum whole plant extract and S. nigrum fruits extract have the capacity to reverse serum levels of ALP, ALT, AST and bilirubin of liver and kidney damages to near normal levels if pathological change occurs. The S. nigrum whole plant extract and S. nigrum fruits extract were found to be safe for the liver and kidney parameters up to 5ml/kg doses. But this extract would have been toxic above 5ml/kg which is considered to be elevated dose. So that safe dosage needs to be identified for children and pregnant women because children have less body resistance and pregnant women may be susceptible to abort since it may induce uterine contraction. Therefore, further studies are required to isolate the active ingredients from the extract of S. nigrum for proper drug development to treat the above mentioned health problems and to conduct further clinical trials.
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    The Effect of Zinc Exposure on the Histology of Liver and Kidney
    (Addis Abeba University, 2014-07) Bekele, Afewerki; Seyoum, Girma (PhD)
    Zinc is one of the most important trace elements in the body that participates in the biological function of several proteins and enzymes. Despite the fact that small quantity of zinc is required for the normal development and metabolism, its effect is toxic when a certain concentration is exceeded. The aim of this paper is to review scientific literatures on the protective and toxic effect of zinc exposure on the histology of liver and kidney. The studies were evaluated in relation to dose of zinc, zinc combination with other toxic metals, duration of exposure, type of animal model used, method of study used and parameter used to measure protective effect of zinc against toxic metals and toxic effect of zinc alone. The different literatures reviewed in this paper used rats, mice, lambs, fishes, ducks. The literature reviewed showed that Zn administration together with Al, Cd, as well as organic solvent such as ethanol has a protective effect against Al, Cd induced toxicity in liver and kidney tissues and ethanol induced toxicity in liver tissue. On the other hand, as zinc dose level and duration of the exposure increases, it act as toxic metal to histology of liver and kidney. Key words: zinc, liver, kidney
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    A Systematic Review of the Histopathological Effects of Ultraviolet Radiation Exposure on the Ocular Structures in Human and Animal Studies
    (Addis Abeba University, 2014-07) Hamba, Niguse; Gebru, Girmai (PhD)
    The transparent anterior segment of the human eye (cornea and lens), as well as neural retina are greatly affected by dose dependent UV radiation exposure. The histopathological changes increased along with irradiation intensity and UV-B exposure. The most severe corneal lesions were observed following eye exposure to some large doses of 0.72 J/cm2 to 1.2 J/cm2. The injuries caused by UV irradiation to cornea are named photokeratitis also known as ultraviolet keratitis. Photokeratitis is characterized by exfoliation of the corneal epithelium, diminished visual perception, inflammation, edema, eye redness, and burning-like pain from the ocular surface. Moreover, UV irradiation can also go deeper through the corneal epithelial layer and provoke inflammatory responses that involve the full corneal thickness The radiation that hits the lens is first filtered by the lens capsule and at 300nm (range from 290 to 315 nm) wavelength, approximately 60% of the radiation is transmitted by the anterior capsule. The transmitted radiation induces apoptosis in the lens epithelial cells and thereafter the cortical fibers which contribute to the formation of lens cortical opacities. Because lens epithelial cells are responsible for maintaining much of the homeostasis of the underlying fibers, damage to lens epithelial cells may also result in abnormalities in lens fibers. For proteins, longevity is commonly assumed to be correlated with long-term retention of native structure. The irradiations ranging from 380-520 nm contribute to degenerate outer nuclear layer area of the retina. Shorter wavelength light also is the most hazardous it is known to generate reactive oxygen species (ROS) in the retina. The retinal pigment epithelium is especially susceptible to oxidative stress because of its high light, oxygen tension, fluorophore and membrane lipid levels. Acute and chronic exposure of the eyelid to UV radiation causes common types of skin lesions around the eyelids that frequently result in basal cell carcinoma, squamous cell carcinoma, sebaceous cell carcinoma, and malignant melanoma In conjunctiva UVB at the dose of 0.72 J/cm2 per day showed conjunctival epithelium metaplasia and loss of goblet cells thereby decreasing of tear quantity
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    Project paper on risk of Congenital Limb Reduction Defects Associated with in Utero Exposure to Oral Contraceptives
    (Addis Abeba University, 2014-07) Diriba, Workineh; Afework, Mekbib (PhD)
    Oral contraceptives are widely used and are generally safe and effective for many women. Oral contraceptives are known also as the Pill, POP, COCPs, OCs, BCs, BC tablets, or birth control pills. This medicine usually contains two types of hormones, estrogens and progestins and, when taken properly, prevents pregnancy. The aim of this project is to review and present the teratogenic effects of Oral contraceptives on the limb development. Allegations that inadvertent pregnancies occurring in users of contraception are associated with congenital anomalies are common. Fortunately, there is little to no scientific basis for such claims. Evaluating these claims requires consideration of the two general mechanisms responsible for human malformation: teratogenesis and mutagenesis. Some study indicate that there is a possibility of a sevenfold (7X) increase in risk of limb reduction defects, Other authors concluded that, exposure to sex hormones during pregnancy doubled the risk for some specific diagnoses, including certain limb defects, but these increases were not statistically significant. Inbred normal adult SWR mice were used to investigate the possible teratogenic effect of Microginon 30 (0.15mg leronogestrel (L) + 0.03mg EE), as an oral contraceptive on fetuses of females receiving doses from day 7 to day 12 of pregnancy. External malformations including abnormal hind limb, abnormal tail and exencephaly have been induced in low frequencies by the doses 0.48L + 0.96E and 1.20L +0.24E mg/kg. An analysis of available epidemiologic data leads the present reviewer to conclude that the use of exogenous hormones during human pregnancy has not been proved to cause developmental abnormality in non-genital organs and tissues. If there are increased risks of non-genital malformations associated with the administration of certain sex steroids, the risks are very small, may not be causal, and are substantially below the spontaneous risk of malformations. Key words: Oral contraceptive, congenital limb reduction defects, pregnancy
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    Histological and Functional Effect of Fluoride on Cerebral Cortex of the Brain
    (Addis Abeba University, 2014-07) Hagos, Selemun; Seyoum, Girma (PhD)
    Fluoride is omnipresent in our environment and has been added to drinking water supplies with a recommended dose. Drinks, tooth pastes, mouth rinses, dietary supplements and foods are also considered as sources of fluorides. This paper reviews the scientific literatures linking fluoride with its effect on histology and function of cerebral cortex of the brain. In this paper the role of fluoride in region specific and sub-cellular distribution of the brain with the relation of its neurotoxicity is highlighted. Studies were assessed by focusing on the dose of fluoride, duration of exposure, type of experimental animals used to measure the effect of fluoride. The literatures reviewed in the present paper used mice, rats and rat offspring as experimental animals. From the literatures reviewed in the present paper, fluoride showed to be neurotoxic chemical which affects the biochemical content of brain, cause weight loss, cause neurodegeneration, histological alternation in hippocampus and cerebral cortex of the brain, disrupting behavioral activities and cause reduction in cognitive and memory functions. Keywords: Cerebral cortex, Histopathological effect, Weight loss, Biochemical change, Neurobehavioral toxicity and Fluoride
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    Project Paper on: the Toxicological Effect of Catha Edulis Forsk (Khat) on the Histology and Function of Liver.
    (Addis Abeba University, 2014-07) Gebreslassie, Adhanom; Seyoum, Girma (PhD)
    In this project paper databases such as Pubmed, Medline, Hinary and Google search, were systematically searched for literature on the different aspects of Catha edulis (Khat) to synthesis, review, and present various research publication on the toxicological effect of khat consumption on the histology and function of liver. Catha edulis (Khat) is a large green shrub that grows at high altitude in the region extending from eastern to Southern Africa, as well as on the Arabian Peninsula; mainly in Ethiopia, Somalia, Kenya, Malawi, Uganda, Tanzania, Congo, Zambia, Zimbabwe, Afghanistan, Yemen and Madagascar. It is known by a variety of names such as, “chat” in Ethiopia, “qat” in Yemen, “mirra” in Kenya and “Khat” in English. The euphoric effects have been demonstrated to arise from the main constituent, (-)-S cathinone. Most of the findings revealed that there is significant result on toxicological effect of Khat consumption on histology and function of liver. This happens as the exposure of Catha edulis in treated liver animal goes from acute to chronic administration starting from the dose of 10% of extracted Catha edulis. In general the project paper showed that Khat treated animals including khat users have elevated activities of hepatic enzymes like Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and bilirubin were as albumin level was decreased as compare to the control group. In addition to this the histo-pathological pictures of the khat treated liver also showed that degenerative alterations include disorganization of hepatic cords, cytoplasmic vacuolization of hepatocytes and invasion of infiltrative inflammatory cells. These result together indicating leakage into extracellular fluid as a result of toxic damage of hepatic tissue by the extract and so it leads to death of the experimental animals including Khat user. Keywords: ALP, ALT, AST, Albumin, Bilirubin, Catha edulis, , Cathinone, Khat, Kupffer cells
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    Evaluations on the Sub-Chronic Toxicity of 70% Ethanolic Seed Extracts of Albizia Gummifera and Millettia Ferruginea on Blood Parameters and Liver and Kidney Tissues in Albino Wistar Rats
    (Addis Abeba University, 2014-10) Debebe, Mekonnen; Makonnen, Eyasu (Professer)
    Albizia gummifera and Millettia ferruginia are plants found in Ethiopia that have different medicinal values. The objective of the present study was to evaluate the toxicological effects of sub-chronic administered hydro-ethanolic (70%) seeds extract of Albizia gummifera and Millettia ferruginea in albino Wistar rats. The seeds of these plants were collected from different areas of Ethiopia. They were dried and crushed to powder and macerated with hydro-alcohol and placed in orbital shaker. The extract was then filtered through Whatman filter paper No.1 and the filtrate o was evaporated to dryness by Rota vapor and further concentrated by water bath at 40 C. The o extract was packed in air tight brown glass bottles and kept in a refrigerator at 4 C. The extract was then administered to rats at different doses to determine the LD50 of the extract and at doses of 125mg/kg/day and 250mg/kg/day for the sub-chronic toxicity study. The LD50 of Albizzia gummifera and Millettia ferrugina were found as 4000mg/kg and 3500mg/kg, respectively. Statistically significant difference in body weight was observed in female rats in the 10th week at 250mg/kg body weight of seeds extract of Albizia gummifera administered group and in the male rats at lowest dose during the 9th and 10th weeks of administration period for seeds extract of Millettia ferruginea. The seeds extract of Albizia gummifera statistically decreased (p ≤ 0.05) MCH in the male rats at both doses; MCHC at both 125mg/kg and 250mg/kg in the female rats; and MCH in the female rats at higher dose and increased RDW-CV in the male rats at both doses. It increased NEUT at the highest dose in both females and males. The seeds extract of Millettia ferruginea decreased (p ≤ 0.05) in the MCHC and MONO of female rats at the highest doses. ALP, ALT and urea were found significant in the female rats administered with 250mg/kg of Millettia ferruginea seeds extract. While, seeds extract of Albizia gummifera increased only urea in male rats at 250mg/kg. Some histopathological changes in liver and kidney were also observed for both plants extracts. There were inflammation, congestions and focal hepatocellular necrosis of the liver tissue. The extracts also produced atrophy of the glomeruli of the kidney. The observed changes in both of the plant seeds extract might have resulted because of the presence of some bioactive ingredients in the extract. Therefore, the active ingredients which might be responsible for toxic insult should be researched with their mechanisms of actions. Key words: Albizia gummifera, Millettia ferruginea, seeds, hydroethanolic extract, toxicity, Wistar Albino Rats.
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    Evaluation of the Acute and Sub-chronic Toxic Effects of Aqueous Leaves Extracts of Artemisia Afra on Liver, Kidney and Some Blood parameters in Wistar Rats at Addis Ababa University on year 2014/2015
    (Addis Abeba University, 2015-08) Eshetu, Nikodimos; Afework, Mekbib (PhD)
    Traditional medicine has remained to be the most affordable and easily accessible source of treatment in the primary healthcare system of resource poor communities and, it is the only means of treatment for such communities. Plants have been the basis for treatment throughout human history, and they are still widely practiced today as part of traditional medicine. The plant Artemisia afra has been shown to display a wide spectrum of biological and pharmacological activities, which provide experimental support for the empiric ethno-pharmacological use of this plant in traditional medicine. However, despite its widespread use, very little is known about its safety and efficacy. This Experimental laboratory based study has been carried out to investigate the acute and subchronic toxic effects of leaves of Artemisia afra on liver and kidney; and some blood parameters in rats. The study was carried out in Department of Anatomy, School of Medicine, Addis Ababa University. The experiments were performed on 59 Wister rats (32 for acute and 27 for subchronic study) based on the OECD guideline they were assigned to each group randomly. The study was conducted from January 2014-July 2015. Various doses of aqueous extract of the leaves were employed for single dose toxicity studies, while the effective dose and triple the effective dose were used for repeated toxicity studies. This study showed that the oral lethal dose (LD50s) is higher than 5000mg/kg. Generally in the acute toxicity study; the general behavior and body weights were not altered in Wister rats administered with doses up to 5000mg/kg. After subchronic study with both doses (600 and 1800mg/kg), there were no significant changes in the overall body weight, the evaluated hematological and most of the biochemical parameters. No death was recorded. In gross observation, the kidneys and liver of treatment groups appear normal in their texture, size or color as compared to the control. Histopathological presentations were generally normal though there were mild mononuclear leukocytic infiltrations around the central venules & portal areas of Wister rats’ liver at both 600 and 1800mg/kg dose in addition minor tubulointerstitial leukocytic infiltrations were observed in small areas of kidney sections administered higher dose. Findings of this study revealed that A. afra is relatively safe. Keywords: A. afra, Traditional medicine, Toxicological assessment
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    Evaluation of acute and sub-chronic Toxicity of Aqueous Leaves Extracts of Maytenus Gracilipes Celastraciae (kombolcha) on Some Blood Parameters and Histopathology of Liver and kidney in Swiss Albino Mice
    (Addis Abeba University, 2015-08) Ayele, Mengistu; Afework, Mekbebk (PhD)
    Human beings use plants for the purpose of disease control and prevention. Maytenus gracilipes celastraciae is a plant having vital traditional medicinal values for treating several human ailments such as for headache, epilepsy, allergic, peptic ulcer, cancer and immflamations. The present study was carried out to evaluate the acute and subchronic toxic effects of aqueous leaves extracts of maytenus gracilipes celastraciae (kombolcha) on some blood parameters and histopathology of liver and kidney in mice. LD50 was determined. The thesis was carried out in Addis Abeba University, College of Health Science, School of Medicine, Department of Anatomy (Histology Laboratory).The study was conducted from May, 2014 -July, 2015.The aqueous leaves extracts of M.gracilipes were employed in swiss albino mice in single oral dose for acute study and repeated oral dose for subchronic study. The LD50, of aqueous extracts of Maytenus gracilipes was found to be 10,000 mg/kg body weight. In the Subchronic study, the extract was administered orally at doses of 700 and 2100 mg/kg/day for 90 days . Body weight, biochemical and hematological parameters were determined at the end of the 90 days of daily extract administration. In sub chronic toxicity study daily oral administration of aqueous extract at 700 and 2100 mg/kg body weight/day did not result in death or significant changes in body weight, hematological and biochemical parameters. Studies on Histopathological examination of selected organs (liver and kidney) showed normal architecture suggesting absence of morphological disturbances. However, at 700 mg/kg body weight liver showed pyknotic nuclei and at 2100mg/kg some cellular infiltrates near the central vein and portal region, where as, in kidney peritubular infiltration and focal mono nuclear leukocytic infiltration was observed at higher dose. Key words: Maytenus gracilipes, Aqueous extract, acute toxicity, subchronic toxicity, Histopathological studies.
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    Evaluation of the Acute and Sub-Chronic Toxicity of Aqueous Extracts of Leaves of Moringa Stenopetala on Some Blood Parameters,and Histopathology of Thyroid Gland, Pancreas and Adrenal Glands in Rats
    (Addis Abeba University, 2015-08) Debela, Lemessa; Afework, Mekbebk (PhD)
    Moringa stenopetala is a plant having vital traditional medicinal value used in human as anti malarial, antihypertensive, anti diabetic and antispasmodic herbal medicine and also has high nutritional value. This study was carried out to investigate the acute and sub-chronic toxicities of aqueous extracts of leaves of M. stenopetala in rats. Changes on body & organ weight, behavior, and gross pathology were investigated. Biochemical, blood parameters, lipid profiles and histopathology of the thyroid gland, adrenal gland and pancreas were also studied. In acute toxicity study, the rats were randomly divided in to four groups (3 rats/group) and the experimental group received 500, 1000, 3000 and 6000mg/kg of the extracts, while the control group received distilled water orally by gavages. In subchronic toxicity study, the experimental rats were randomly divided into three groups 6 rats/group for female and 4 rats/group for males. The experimental group in both sexes received 500 and 1500mg/kg of the extract in group I and II respectively, whereas the control group received distilled water for 90 days once daily. After 90 days of administration of the extract, the rats were anesthetized by diethyl ether then the blood samples were collected and the rats were scarified and the thyroid gland, adrenal glands and pancreas were removed, fixed, processed and stained for histological examination. In acute toxicity study, rats treated with up to dose of 6000mg/kg body weight showed no toxic signs on behavior, gross pathology and body weight .In the sub-chronic toxicity study treated rats showed no significant changes on behavior, gross pathology, hematological (except slight decrement in WBC & platelets, p>0.05) and biochemical parameters (except organ & body weight increment p>0.05), thyroid function test (except increment in TSH & T3, decrement in T4) as compared with control rats. Lipid profiles also showed changes but not significant statistically. There were no significant difference in the gross and histopathology of the thyroid gland, adrenal gland and pancreas of the experimental rats as compared to control group. These results show that the aqueous extraction of M.stenopetala did not produce adverse effects in experimental rats after acute and sub-chronic treatment. Increment in TSH level might be due to the effect of the plant extract on hypothalamus, but change in T3 & T4 is related to its effect on the gland. Key words: M.stenopetala, Toxicity, aqueous extract of leaves of M.stenopetala, TMP
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    Evaluation of the Acute and Subacute Toxicity of Aqueous Leaves Extracts of Artemisia Afra on Brain, Heart and Suprarenal Gland in Swiss Albino Mice
    (Addis Abeba University, 2015-08) Mekonen, Ketema; Afework, Mekbeb (PhD)
    Having primary health care is a human right which is fulfilled by western country because of expansion of health infrastructure, and increased quantity and quality of health professionals. But many developing countries including Ethiopia are yet far from achieving this. In Ethiopia, the majority of population relay on traditional medicine as a source of health care. The most common sources of traditional medicine are plants. A.afra is one of these plants that are used to treat different aliments. The aim of the present study was to investigate the toxic effects of A.afra on brain, heart and suprarenal glands. The study was conducted at Addis Ababa University, College of Health Science, School of Medicine, Department of Anatomy & Department of Physiology from Jan, 2014 to July, 2015. The plant was collected from Bale National park in Oromia Regional State. The plant was air dried and aqueous extract was prepared. In this research a total of 54 male and female mice of 8-12 weeks of age weighing 25-30g were used. The extract was given by oral rout in both acute and subacute study. The doses for acute toxicity study were 200mg/kg, 700mg/kg, 1200mg/kg, 2200mg/kg, 3200mg/kg, 4200mg/kg and 5000mg/kg of body weight, while for subacute toxcicy study a doses of 600mg/kg(low dose) and 1800mg/kg(high dose) of body weight were used. LD50 was grounded to be greater or above 5000mg/kg which indicates that the plant is relatively safe. There were no observed signs of toxicity at the lower three doses, although mild toxicity sign was observed at the higher dose level in dose dependent manner. In the subacute study, two treatment groups 600mg/kg and 1800mg/kg and one control group containing both sexes were used. Weights of mice were measured weekly and individual mice were observed for possible toxicity sign. At the end of 28 days, the animals were scarified and organs were harvested and processed for microscopic examination. No toxicity signs were observed in all treatment groups. There were also no significant weight changes between the treated and control group. On microscopic examination of the brain, heart and suprarenal glands no sign of cellular injury was observed. From this study it can be concluded that A.afra is relatively safe in mice. Key words: Traditional medicine, A.afra, Toxicity study, LD50, Histopathology