Makonnen, Eyasu (Professer)Alebachew, Mebratu2018-06-122023-11-292018-06-122023-11-292009-05http://etd.aau.edu.et/handle/123456789/440Toxicological 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 parametersen-USV. Bipontini, Swiss Albino Mice, Liver, Kidney, Hematological and Biochemical ParametersThesis