Comparative protective effect of N‐acetyl cysteine and tetramethylpyrazine in rats with gentamicin nephrotoxicity

Abstract

Gentamicin (GM) is used against serious and life‐threatening infections, but its use is limited by the occurrence of nephrotoxicity, which involves the generation of free radicals. In this work we tested the effect of a compound with antioxidant properties, tertamethylpyrazine (TMP), on GM‐induced nephrotoxicity, and compared it with an established anti‐oxidant compound N‐acetyl cysteine (NAC). Six groups of rats were studied: (1) control, treated orally (p.o.) and intraperitoneally (i.p.) with saline; (2) treated i.p. with GM (80 mg kg‐1 per day for 6 days); (3) TMP, given p.o. (100 mg kg‐1 per day for 10 days) + GM (same dose as above during the last 6 days); (4) NAC, given i.p. (500 mg kg‐1 per day for 10 days) + GM as above; (5) TMP (100 mg kg‐1 per day for 10 days) + saline; (6) NAC (500 mg kg‐1 per day for 10 days) + saline. GM nephrotoxicity was characterized by reduced creatinine clearance, increased creatinine and urea concentrations in plasma. These functional and structural alterations were prevented or ameliorated by NAC treatment, while TMP had only a slight mitigating effect. The concentration of GM in the renal cortex of the rats given GM + NAC (but not TMP) was lower than that found in rats treated with GM alone. The mechanism by which NAC and, to a lesser extent TMP, protected against GM‐induced nephrotoxicity may be related, at least in part, to the decrease in oxidative stress in renal cortex.