Evaluation of Renoprotective Effects of Euclea Divinorum Hierns Against Gentamicininduced Nephrotoxicity in Rats
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Date
2011-10
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Addis Ababa University
Abstract
Despite 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.
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Keywords
Gentamicin, Gentamicin-induced nephrotoxicity