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|Title: ||Reversal of cisplatin-induced carnitine deficiency and energy starvation by propionyl-l-carnitine in rat kidney tissues|
|Authors: ||Bakheet, Saleh A.|
Al-Shabanah, Othman A.
Sayed-Ahmed, Mohamed M.
Aleisa, Abdulaziz M.
Al-Majed, Abdulhakeem A
Al-Yahya, Abdulaziz A
Al-Rejaie, Salim S
|Keywords: ||Cisplatin-Induced Carnitine Deficiency|
Rat Kidney Tissues
|Issue Date: ||2007 |
|Publisher: ||Blackwell Publishing Asia|
|Citation: ||Clinical and Experimental Pharmacology and Physiology: 34; 1252–1259|
|Abstract: ||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
(NOx), 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
NOx and the CDDP-induced decrease in total carnitine, GSH,
ATP and ATP/ADP in kidney tissues.
5. Histopathological examination of kidney tissues from CDDPtreated
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.|
|Appears in Collections:||College of Pharmacy|
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