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

B. H. Ali, S. Al-Salam, I. Al-Husseinia, A. Nemmar

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21 Citations (Scopus)

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), a major constituent of the Chinese medicinal plant Lingusticum wallichi, 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 (80mg 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, increased urinary excretion of N-acetyl-β-D-glucosaminidase (NAG) and total protein. These functional and structural alterations were prevented or ameliorated by NAC treatment, while TMP had only a slight mitigating effect that was less marked than that produced by NAC. 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 by about 25%. 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.

Original languageEnglish
Pages (from-to)302-307
Number of pages6
JournalJournal of Applied Toxicology
Volume29
Issue number4
DOIs
Publication statusPublished - May 2009

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Keywords

  • Gentamicin
  • N-acetyl cysteine
  • Rats
  • Tertamethylpyrazine

ASJC Scopus subject areas

  • Toxicology

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