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Article Type

Original Study

Abstract

Background As a highly effective antibiotic, gentamicin is used in the treatment of serious and life-threatening gram-negative infections. L-arginine (2-amino-5-guanidino-pentanoic acid) has a protective role on renal failure that induced by gentamicin administration and it may decrease the tubular reabsorption of another cationic substance, gentamicin due to its cationic structure. The aim of this study is to determine the influence of gender on nephroprotective effects of L-arginine (Arg) and/or taurine (Tau) on gentamicin (G) induced nephrotoxicity. Methods Adult Sprague-Dawley albino rats of both sexes (150-200 g, 48 male and 48 female), were bred from the animal unit of National Nutrition Institute, Cairo, Egypt. Male rats were divided randomly into 8 groups (n=6 per group) and the following treatments were given: Group 1 (negative control group): saline (2 ml/Kg/day, i.p); Group 2 (positive control group): was injected with G (100 mg/kg b.wt./day, i.p); Group 3 injected with G and treated with Arg (1.6 gm/kg b.wt /day, p.o); Group 4 injected with G and treated with Tau (0.75 gm/kg b.wt/day,i.p) and Group 5 injected with G and treated with combination of Arg and Tau at the same previously mentioned doses. The tested amino acids and their combination were also administrated to healthy rats (three groups) for ten consecutive days. Female rats were divided at random into eight groups and treated in the same fashion as above. Results Gentamicin administration resulted in nephrotoxicity as evidenced by significant elevation in serum creatinine (122% and 127%) and blood urea nitrogen (BUN) (18.3% and 117%), significant reduction in creatinine clearance (30% and 46.9%), proteinuria (250% and 372%), sharply elevated levels of urinary alkaline phosphatase (ALP) (267% and 415%) and potassium (244% and 376%) and decreased level of serum ALP (10.2% and 31.9%) in males and females, respectively. Gentamicin did not affect serum potassium in both males and females and on serum sodium in males; however, it increased serum sodium in females by 27%. Also, gentamicin injection enhanced lipid peroxidation as indicated by the elevated levels of renal malondialdehyde (MDA) (46.7% and 22.8%) and nitric oxide (NO) (48% and 72%) and the depressed level of reduced glutathione (GSH) in kidney (55% and 45%) and whole blood (5.7% and 8.8%) in male and female rats, respectively, as compared with normal rats. Also, the activity of erythrocyte Cu, Zn superoxide dismutase (SOD) was reduced (10.1%) in males but not in females as compared with normal rats. Supplementation with Arg and/or Tau attenuated G induced nephrotoxicity in male and female rats. These nephroprotective effects were more pronounced in females. Conclusion The results of the present study indicate that female Sprague-Dawley rats are more sensitive to the nephrotoxic effects of G. Treatment with Arg and/or Tau exerted a nephroprotective impact, which is gender specific.

Keywords

Arginine, sex differences, gentamicin, nephrotoxicity, taurine

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