L-Carnitine attenuates ifosfamide-induced carnitine deficiency and decreased intramitochondrial CoA-SH in rat kidney tissues.

Abstract

BACKGROUND:

The effects of L-carnitine on ifosfamide (IFO)-induced Fanconi syndrome have not been studied to date. This study aimed to investigate, on a mechanism basis, whether L-carnitine could prevent the development of IFO-induced Fanconi syndrome in rats.

METHODS:

Adult male Wistar albino rats were assigned to 1 of 4 treatment groups: group 1 (control) rats were given daily intraperitoneal (i.p.) injections of normal saline for 10 consecutive days; group 2 (L-carnitine) rats were given L-carnitine (200 mg/kg per day, i.p.) for 10 consecutive days. Rats of group 3 (IFO) received normal saline for 5 days, followed by IFO (50 mg/kg per day, i.p.) for 5 consecutive days. Rats of group 4 (IFO plus L-carnitine) received L-carnitine for 5 days before and 5 days concomitant with IFO.

RESULTS:

Administration of IFO for 5 consecutive days significantly increased serum creatinine, blood urea nitrogen (BUN), urinary carnitine excretion, intramitochondrial acetyl-CoA and thiobarbituric acid reactive substances (TBARS), and significantly decreased total carnitine, intramitochondrial CoA-SH, ATP and ATP/ADP ratio, and reduced glutathione (GSH) in kidney tissues. Administration of L-carnitine to IFO-treated rats resulted in a complete reversal of the increase in serum creatinine, BUN, urinary carnitine excretion and intramitochondrial acetyl-CoA, and of the decrease in total carnitine, intramitochondrial CoA-SH, ATP and GSH, induced by IFO, to the control values.

CONCLUSIONS:

L-Carnitine prevents the development of IFO-induced Fanconi syndrome by increasing intracellular carnitine content and intramitochondrial CoA-SH, with the consequent improvement in mitochondrial oxidative phosphorylation and energy production, as well as its ability to decrease oxidative stress.

• Authors: Mohamed M Sayed-Ahmed
• Journal: Journal of nephrology (J Nephrol) 2011 Jul-Aug Vol. 24 Issue 4 Pg. 490-8 ISSN: 1724-6059 [Electronic] Italy
• PMID: 21404227 (Publication Type: Journal Article)

Chemical References

• Thiobarbituric Acid Reactive Substances
• Vitamin B Complex
• Acetyl Coenzyme A
• Adenosine Triphosphate
• Creatinine
• Carnitine
• Coenzyme A
• Ifosfamide

Topics

• Acetyl Coenzyme A (metabolism)
• Adenosine Triphosphate (metabolism)
• Animals
• Blood Urea Nitrogen
• Carnitine (deficiency, pharmacology, urine)
• Coenzyme A (metabolism)
• Creatinine (blood)
• Disease Models, Animal
• Fanconi Syndrome (chemically induced, metabolism, prevention & control)
• Ifosfamide
• Kidney (drug effects, metabolism)
• Male
• Mitochondria (metabolism)
• Rats
• Rats, Wistar
• Thiobarbituric Acid Reactive Substances (metabolism)
• Vitamin B Complex (pharmacology)
• Vitamin B Deficiency (chemically induced)