Comparative protective effect of N-acetyl cysteine and tetramethylpyrazine in rats with gentamicin nephrotoxicity.
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 (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, increased urinary excretion of N-acetyl-beta-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.
Ali
B H
BH
Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Al Khod, Oman. alibadreldin@hotmail.com
Al-Salam
S
S
Al-Husseini
I
I
Nemmar
A
A
D000111:Acetylcysteine / Q000494:pharmacology*; D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism; D005839:Gentamicins; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020011:Protective Agents; D011500:Protein Synthesis Inhibitors; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000378:metabolism; D014563:Urodynamics / Q000187:drug effects
D000975:Antioxidants; D005839:Gentamicins; D020011:Protective Agents; D011500:Protein Synthesis Inhibitors; D011719:Pyrazines; D014508:Urea; D003404:Creatinine; C017953:tetramethylpyrazine; D000111:Acetylcysteine