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L-arginine ameliorates kidney function and urinary bladder sensitivity in experimentally-induced renal dysfunction in
Mahmoud A Mansour1, Othman A Al-Shabanah, Hassan A El-Khashef
1Department of Pharmacology, College of Pharmacy, King Saud University, P.O Box 2457, Riyadh 11451, Saudi Arabia. mansour1960us@yahoo.com
Journal of Biochemistry and Molecular Biology
|August 5, 2003
Summary
L-arginine supplementation significantly protected against cisplatin-induced kidney damage by improving renal function and reducing oxidative stress. NG-nitro-L-arginine methyl ester (L-NAME) did not offer protection, suggesting a specific role for L-arginine in mitigating cisplatin nephrotoxicity.
Area of Science:
- Nephrology
- Pharmacology
- Biochemistry
Background:
- Cisplatin (CDDP) is a potent chemotherapeutic agent with significant nephrotoxicity.
- CDDP-induced renal dysfunction is characterized by impaired kidney function and increased oxidative stress.
- Investigating protective agents against CDDP nephrotoxicity is crucial for improving cancer therapy.
Purpose of the Study:
- To evaluate the protective effects of L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) against cisplatin-induced renal dysfunction.
- To elucidate the mechanisms underlying L-arginine's potential renoprotective properties.
- To assess the impact of these agents on biochemical and functional markers of kidney injury.
Main Methods:
- CDDP was administered to induce renotoxicity.
- Animals were treated with either L-arginine or L-NAME prior to and after CDDP injection.
- Renal function was assessed by measuring serum urea, creatinine, and albumin levels.
- Oxidative stress markers, including glutathione peroxidase (GSH-Px), catalase activities, and malondialdehyde (MDA) levels, were quantified in kidney homogenates.
- Ex vivo isolated urinary bladder rings were used to assess acetylcholine (ACh) sensitivity.
Main Results:
- CDDP treatment significantly increased urinary bladder sensitivity to ACh, elevated serum urea and creatinine, and decreased serum albumin.
- CDDP administration led to decreased GSH-Px and catalase activities and increased MDA levels in kidney tissues.
- L-arginine administration significantly ameliorated CDDP-induced renal dysfunction, restoring normal bladder responses to ACh and improving renal function indices.
- L-arginine treatment prevented the increase in MDA and the reduction in GSH-Px and catalase activities.
- L-NAME treatment offered no protection against CDDP-induced renal dysfunction.
Conclusions:
- L-arginine effectively attenuates cisplatin-induced kidney injury.
- L-arginine's renoprotective effects may be linked to its antioxidant properties and modulation of nitric oxide pathways.
- L-arginine shows promise as a therapeutic agent to mitigate CDDP nephrotoxicity and potentially enhance the therapeutic index of cisplatin chemotherapy.