Effect of lithium on cyclosporin induced nephrotoxicity in rats

Tariq, Mohammad, Morais, Christudas, Sobki, Samia, Al Sulaiman, Mohammed and Al Khader, Abdullah (2000) Effect of lithium on cyclosporin induced nephrotoxicity in rats. Renal Failure, 22 5: 545-560. doi:10.1081/JDI-100100896


Author Tariq, Mohammad
Morais, Christudas
Sobki, Samia
Al Sulaiman, Mohammed
Al Khader, Abdullah
Title Effect of lithium on cyclosporin induced nephrotoxicity in rats
Journal name Renal Failure   Check publisher's open access policy
ISSN 0886-022X
1525-6049
Publication date 2000
Sub-type Article (original research)
DOI 10.1081/JDI-100100896
Volume 22
Issue 5
Start page 545
End page 560
Total pages 16
Place of publication New York, NY, United States
Publisher Informa Healthcare
Language eng
Abstract Psychoactive drugs provide essential intervention in the care of transplant recipients, yet little is known of their interaction with immuno-suppressants such as cyclosporin (CSA). Lithium (Li) is an invaluable drug for the treatment of manic disorders in organ transplant patients. As both these drugs are known to produce renal toxicity, the concomitant use of CSA and Li may be potentially harmful. The present study was undertaken to investigate the effect of CSA and Li chloride individually and in combination on renal structure and function of rats. Male Sprague-Dawley rats were divided into the following eight groups of seven animals each: Group 1, control (vehicle only); group 2, Li (2mEq/kg i.p.) alone; group 3, CSA 12.5 mg/kg (subcutaneous); group 4, CSA 25 mg/kg; group 5, CSA 50 mg/kg; group 6, CSA 12.5 mg/kg + Li; group 7, CSA 25 mg/kg + Li; and group 8, CSA 50 mg/kg + Li. The drugs were given once a day for seven days; Li being administered 30 min before CSA. Twenty four hours after the last dose of drugs the animals were sacrificed and blood samples were analyzed for blood urea nitrogen (BUN), serum creatinine (SCr), CSA and Li levels. The left kidney was analyzed for malondialdehyde (MDA) and conjugated dienes (CD) levels and right kidney was used for histopathological studies. Our results showed that Li alone did not produce any significant renal toxicity, whereas CSA dose dependently caused structural and functional changes in kidneys. However, significantly higher structural and functional impairment was observed in the animals treated with Li plus CSA as compared to CSA alone treated animals. Several fold increase in blood Li level was also noticed in the rats concomitantly treated with CSA and Li. A significant increase in MDA and CD in the rats treated with CSA plus Li suggests the role of oxidative stress in drug induced nephrotoxicity. These findings clearly demonstrate that even non toxic doses of Li may significantly exacerbate CSA induced nephrotoxicity in rats. The enhanced nephrotoxicity following concomitant use of these drugs may be attributed to significant increase in the bioavailability of Li and enhanced oxidative stress. Further clinical studies are warranted to investigate the interaction of these nephrotoxic drugs in human subjects.
Keyword Cyclosporin
Lithium
Nephrotoxicity
Free radicals
Lipid peroxidation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Mon, 20 Dec 2010, 13:59:18 EST