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KMID : 0880520100460030156
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Chonnam Medical Journal
2010 Volume.46 No. 3 p.156 ~ p.162
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Effects of Antioxidants in Cisplatin-Induced Renal Tubular Apoptosis
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Bae Eun-Hui
Lee Jong-Un
Ma Seong-Kwon
Kim Soo-Wan
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Abstract
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The present study was designed to evaluate the possible renoprotective effects of alpha-lipoic acid (α-LA) in cisplatin-induced nephropathy and its role in inflammation and apoptosis in the kidney. Male Sprague-Dawley rats, weighing 180~200 g, were used. One group of rats was injected with cisplatin (6 mg/kg intraperitoneally). Another group of rats was injected with cisplatin and co-treated with α-LA. Rats that received an injection of vehicle only served as controls. Four days later, the mRNA expression of Bax and Bcl-2 was determined by real-time PCR. The protein expression of ED-1, cyclooxygenase-2 (COX2), heat shock protein 72 (HSP72), Bax, and Bcl-2 was determined in the kidney by immunoblotting. Apoptosis was determined by TUNEL staining. Cisplatin-treated rats had decreased creatinine clearance and increased plasma creatinine levels compared with controls. α-LA treatment lowered plasma creatinine levels and increased creatinine clearance. In cisplatin-treated rats, the mRNA expression of Bcl-2 was decreased, which was attenuated by α-LA treatment. The protein expression of ED-1, COX 2, HSP72, cleaved caspase-3, and Bax in the kidney was increased compared with controls, whereas that of Bcl-2 was decreased, and these changes were counteracted by α-LA treatment. TUNEL-positive cells were increased, in association with an increased protein expression of Bax and cleaved caspase-3 in the kidney of cisplatin-induced nephropathy, which was counteracted by α-LA treatment. These findings suggest that α-LA is effective in preventing the progression of cisplatin-induced nephropathy, the mechanism of which is associated with anti-inflammation and anti-apoptotic effects.
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KEYWORD
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Oxidative stress, Cisplatin, Apoptosis, Inflammation
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