Engidawork, Ephrem (PhD)Asres, Kaleab(PhD)Feyissa, Tadiwos2018-06-272023-11-062018-06-272023-11-062011-10http://etd.aau.edu.et/handle/123456789/4022Despite their nephrotoxicity and ototoxicity, aminoglycoside antibiotics (such as gentamicin and amikacin) are still considered to be important agents against lifethreatening infections owing to their bactericidal efficacy, synergism with ß-lactam agents, low cost, limited bacterial resistance and a post-antibiotic effect. The goal of reducing or protecting against their nephrotoxicity will increase the safety of the drugs and significantly improve the quality of life of patients taking aminoglycosides. In this study, the renoprotective effects of the crude extract and solvent fractions of Euclea divinorum H. leaves was evaluated against gentamicin-induced nephrotoxicity in rats as the dried roots of the plant is crushed and swallowed for some kidney problems in some regions of Ethiopia. For the assessment of gentamicin nephrotoxicity biochemical and morphologic parameters were measured. Rats were divided into seven experimental groups of 6 (three male and three female) each. The first group served as a control (CON, group I) and given vehicle (Tween 80, 2%, v/v) in water orally. The second group (GEN, group II) were treated with normal saline intraperitonally for two days and afterwards gentamicin (100 mg/kg/day) for eight days. The rest of the groups received crude extract at three different doses 200 mg/kg (C200, group III), 150 mg/kg (C150, group IV) and 100 mg/kg (C100, group V), methanol fraction (M100, group VI) and aqueous fraction (W100, group VII) of E. divinorum orally for two days before and eight days concomitantly with gentamicin (100 mg/kg/day, intraperitonally). Gentamicin produced changes in renal indices, including increase in blood urea nitrogen (BUN) (111.46%, p<0.001) and creatinine (183.26%, p<0.001) levels compared to CON. Moreover, it also caused alterations in redox parameters such as increase in lipid peroxidation (83.89%, p<0.01) and decrease in catalase (CAT) activity (81.8%, p<0.05), superoxide dismutase (SOD) activity (40.3%, p<0.01) and glutathione (GSH) levels (38.06%, p<0.01) when compared to CON. Morphologic pathologic analysis also revealed a decrease in body weight (p<0.001), an increase in normalized kidney weight (42.34%, p<0.001) and more extensive/marked tubular necrosis, inflammation, hyaline vi ii casts in tubular lumen, hydropic degeneration and disintegrated nucleus in GEN group compared to CON. Pre- and co-treatment with the crude extract and solvent fractions E. divinorum leaves reversed alterations caused by gentamicin as evidenced by decrease in normalized kidney weight (p<0.05 in C150, C100 and W100; p<0.001 in M100), BUN (p<0.05 in C200; p<0.001 in C150, C100, M100 and W100), serum creatinine (p<0.05 in C200; p<0.01 in C150; p<0.001 in C100, M100 and W100), lipid peroxidation (p<0.05 in all cases) and increase in body weight (p<0.05 in C200 and C150; p<0.01 in C100, M100 and W100), CAT activity (p<0.05 in C200 and C150; p<0.01 in W100; p<0.001 in C100 and M100), SOD activity (p<0.05 in C200, C150, C100 and W100; p<0.01 in M100) and GSH level (p<0.05 in all cases). Further, crude extract and solvent fractions of the plant were observed to mitigate the histological renal changes associated gentamicin. Based on the study findings, it could be concluded that gentamicin induces generation of free radicals leading to oxidative damage to kidneys and acute renal failure. E. divinorum might act in the kidney as a potent scavenger of free radicals to prevent the toxic effects of gentamicin with a maximal nephroprotection by the methanol fraction followed by aqueous fraction and then by crude extract. In conclusion, E. divinorum might be a potential protective agent against drugs-induced nephrotoxicity besides its traditional uses. Key terms: gentamicin, gentamicin-induced nephrotoxicity, nephroprotection, Euclea divinorum, Dedeho and Mi'essa.enGentamicinGentamicin-induced nephrotoxicityThesis