title: Reversal of cisplatin-induced carnitine deficiency and energy starvation by propionyl-L-carnitine in rat kidney tissues.
abstract: 1. The present study examined whether propionyl-L-carnitine (PLC) could prevent the development of cisplatin (CDDP)-induced acute renal failure in rats. 2. Forty adult male Wistar albino rats were divided into four groups. Rats in the first group were injected daily with normal saline (2.5 mL/kg, i.p.) for 10 consecutive days, whereas the second group received PLC (250 mg/kg, i.p.) for 10 consecutive days. Animals in the third group were injected daily with normal saline for 5 consecutive days before and after a single dose of CDDP (7 mg/kg, i.p.). Rats in the fourth group received a combination of PLC (250 mg/kg, i.p.) for 5 consecutive days before and after a single dose of CDDP (7 mg/kg, i.p.). On Day 6 following CDDP treatment, animals were killed and serum and kidneys were isolated for analysis. 3. Injection of CDDP resulted in a significant increase in serum creatinine, blood urea nitrogen (BUN), thiobarbituric acid-reactive substances (TBARS) and total nitrate/nitrite (NO(x)), as well as a significant decrease in reduced glutathione (GSH), total carnitine, ATP and ATP/ADP in kidney tissues. 4. Administration of PLC significantly attenuated the nephrotoxic effects of CDDP, manifested as normalization of the CDDP-induced increase in serum creatinine, BUN, TBARS and NO(x) and the CDDP-induced decrease in total carnitine, GSH, ATP and ATP/ADP in kidney tissues. 5. Histopathological examination of kidney tissues from CDDP-treated rats showed severe nephrotoxicity, in which 50-75% of glomeruli and renal tubules exhibited massive degenerative changes. Interestingly, administration of PLC to CDDP-treated rats resulted in a significant improvement in glomeruli and renal tubules, in which less than 25% of glomeruli and renal tubules exhibited focal necrosis. 6. Data from the present study suggest that PLC prevents the development of CDDP-induced acute renal injury by a mechanism related, at least in part, to the ability of PLC to increase intracellular carnitine content, with a consequent improvement in mitochondrial oxidative phosphorylation and energy production, as well as its ability to decrease oxidative stress. This will open new perspectives for the use of PLC in the treatment of renal diseases associated with or secondary to carnitine deficiency.
authors.affiliation: Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Abdulaziz M
authors.initials: AM
authors.lastname: Aleisa
authors.forename: Abdulhakeem A
authors.initials: AA
authors.lastname: Al-Majed
authors.forename: Abdulaziz A
authors.initials: AA
authors.lastname: Al-Yahya
authors.forename: Salim S
authors.initials: SS
authors.lastname: Al-Rejaie
authors.forename: Saleh A
authors.initials: SA
authors.lastname: Bakheet
authors.forename: Othman A
authors.initials: OA
authors.lastname: Al-Shabanah
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Sayed-Ahmed
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents; D001806:Blood Urea Nitrogen; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000172:deficiency* / Q000378:metabolism / Q000627:therapeutic use; D002945:Cisplatin; D003404:Creatinine / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D020011:Protective Agents / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D009566:Nitrates; D009573:Nitrites; D020011:Protective Agents; D017392:Thiobarbituric Acid Reactive Substances; C003223:propionylcarnitine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003404:Creatinine; D005978:Glutathione; D002945:Cisplatin; D002331:Carnitine