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NDT Advance Access published online on September 8, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp457
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© The Author 2009. Published by Oxford University Press [on behalf of ERA-EDTA]. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Increased urinary losses of carnitine and decreased intramitochondrial coenzyme a in gentamicin-induced acute renal failure in rats

Othman A. Al-Shabanah, Abdulaziz M. Aleisa, Abdulaziz A. Al-Yahya, Salim S. Al-Rejaie, Saleh A. Bakheet, Amal G. Fatani and Mohamed M. Sayed-Ahmed

Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Kingdom of Saudi Arabia

Correspondence and offprint requests to: Mohamed M. Sayed-Ahmed; E-mail: sayedahmedmm{at}hotmail.com



  Abstract

Background. This study examined whether carnitine deficiency is a risk factor and should be viewed as a mechanism during the development of gentamicin (GM)-induced ARF as well as exploring if carnitine supplementation could offer protection against this toxicity.

Methods. Adult male Wistar albino rats were assigned to one of six treatment groups: group 1 (control) rats were given daily intraperitoneal (I.P.) injections of normal saline for 8 consecutive days; groups 2, 3 and 4 rats were given GM (80 mg/kg/day, I.P.), L-carnitine (200 mg/kg/day, I.P.) and D-carnitine (250 mg/kg/day, I.P.), respectively, for 8 consecutive days. Rats of group 5 (GM plus D-carnitine) received a daily I.P. injection of D-carnitine (250 mg/kg/day) 1 h before GM (80 mg/kg/day) for 8 consecutive days. Rats of group 6 (GM plus L-carnitine) received a daily I.P. injection of L-carnitine (200 mg/kg/day) 1 h before GM (80 mg/kg/day) for 8 consecutive days.

Results. GM significantly increased serum creatinine, blood urea nitrogen (BUN), urinary carnitine excretion, intramitochondrial acetyl-CoA and total nitrate/nitrite (NOx) and thiobarbituric acid reactive substances (TBARS) in kidney tissues and significantly decreased total carnitine, intramitochondrial CoA-SH, ATP, ATP/ADP and reduced glutathione (GSH) in kidney tissues. In carnitine-depleted rats, GM caused a progressive increase in serum creatinine, BUN and urinary carnitine excretion and a progressive decrease in total carnitine, intamitochondrial CoA-SH and ATP. Interestingly, L-carnitine supplementation resulted in a complete reversal of the increase in serum creatinine, BUN, urinary carnitine excretion and the decrease in total carnitine, intramitochondrial CoA-SH and ATP, induced by GM, to the control values. Moreover, the histopathological examination of kidney tissues confirmed the biochemical data, where L-carnitine prevents and D-carnitine aggravates GM-induced ARF.

Conclusions. (i) GM-induced nephrotoxicity leads to increased urinary losses of carnitine; (ii) carnitine deficiency is a risk factor and should be viewed as a mechanism during the development of GM-induced ARF; and (iii) carnitine supplementation ameliorates the severity of GM-induced kidney dysfunction by increasing the intramitochondrial CoA-SH/acetyl-CoA ratio and ATP production.

Keywords: carnitine deficiency; D-carnitine; gentamicin; L-carnitine; nephrotoxicity

Received for publication: 28. 6.09
Accepted in revised form: 12. 8.09


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