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Increased urinary losses of carnitine and decreased intramitochondrial coenzyme A in gentamicin-induced acute renal failure in rats.
Nephrol Dial Transplant. 2010 Jan; 25(1):69-76.ND

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.

Authors+Show Affiliations

Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Kingdom of Saudi Arabia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19737869

Citation

Al-Shabanah, Othman A., et al. "Increased Urinary Losses of Carnitine and Decreased Intramitochondrial Coenzyme a in Gentamicin-induced Acute Renal Failure in Rats." Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 25, no. 1, 2010, pp. 69-76.
Al-Shabanah OA, Aleisa AM, Al-Yahya AA, et al. Increased urinary losses of carnitine and decreased intramitochondrial coenzyme A in gentamicin-induced acute renal failure in rats. Nephrol Dial Transplant. 2010;25(1):69-76.
Al-Shabanah, O. A., Aleisa, A. M., Al-Yahya, A. A., Al-Rejaie, S. S., Bakheet, S. A., Fatani, A. G., & Sayed-Ahmed, M. M. (2010). Increased urinary losses of carnitine and decreased intramitochondrial coenzyme A in gentamicin-induced acute renal failure in rats. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 25(1), 69-76. https://doi.org/10.1093/ndt/gfp457
Al-Shabanah OA, et al. Increased Urinary Losses of Carnitine and Decreased Intramitochondrial Coenzyme a in Gentamicin-induced Acute Renal Failure in Rats. Nephrol Dial Transplant. 2010;25(1):69-76. PubMed PMID: 19737869.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased urinary losses of carnitine and decreased intramitochondrial coenzyme A in gentamicin-induced acute renal failure in rats. AU - Al-Shabanah,Othman A, AU - Aleisa,Abdulaziz M, AU - Al-Yahya,Abdulaziz A, AU - Al-Rejaie,Salim S, AU - Bakheet,Saleh A, AU - Fatani,Amal G, AU - Sayed-Ahmed,Mohamed M, Y1 - 2009/09/08/ PY - 2009/9/10/entrez PY - 2009/9/10/pubmed PY - 2010/3/20/medline SP - 69 EP - 76 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol Dial Transplant VL - 25 IS - 1 N2 - 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. SN - 1460-2385 UR - https://www.unboundmedicine.com/medline/citation/19737869/Increased_urinary_losses_of_carnitine_and_decreased_intramitochondrial_coenzyme_A_in_gentamicin_induced_acute_renal_failure_in_rats_ L2 - https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gfp457 DB - PRIME DP - Unbound Medicine ER -