title: 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.affiliation: Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia. sayedahmedmm@hotmail.com
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Sayed-Ahmed
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001806:Blood Urea Nitrogen; D002331:Carnitine / Q000172:deficiency* / Q000494:pharmacology* / Q000652:urine; D003065:Coenzyme A / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005198:Fanconi Syndrome / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D007069:Ifosfamide; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014803:Vitamin B Complex / Q000494:pharmacology*; D014804:Vitamin B Deficiency / Q000139:chemically induced
chemical_list: D017392:Thiobarbituric Acid Reactive Substances; D014803:Vitamin B Complex; D000105:Acetyl Coenzyme A; D000255:Adenosine Triphosphate; D003404:Creatinine; D002331:Carnitine; D003065:Coenzyme A; D007069:Ifosfamide