Doxorubicin induced nephrotoxicity: protective effect of nicotinamide.

Doxorubicin induced nephrotoxicity: protective effect of nicotinamide.
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DOI:
10.1155/2011/390238
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发表时间:
2011
影响因子:
--
通讯作者:
Oktem G
Oktem G
中科院分区:
其他
文献类型:
--
作者:
Ayla S;Seckin I;Tanriverdi G;Cengiz M;Eser M;Soner BC;Oktem G

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导言。肾毒性是蒽环类抗生素的重要副作用之一。本研究旨在探讨抗氧化剂烟酰胺(NAD)对阿霉素(DXR)肾毒性的影响。方法:研究方法。将大鼠分为对照组、NAD组、阿霉素组(20 mg/kg,i.p)。地塞米松+NAD(2 0 0 mg/kg,i.p.)组。第10天结束时,取肾组织进行光镜观察和分析。测定组织中过氧化氢酶(CAT)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GPx)、诱导型一氧化氮合酶(INOS)和内皮型一氧化氮合酶(ENOS)活性。结果。阿霉素组肾组织中CAT、GPX、GSH活性降低,Po升高。阿霉素组肾组织出现肾小球空泡化、变性,与鲍曼囊粘连,肾小管、肾小球毛细血管基底膜增厚、不整齐等病理改变。组织病理学检查显示,NAD可部分阻止DXR所致的肾小管和肾小球损伤。结论。NAD预处理对DXR所致肾毒性有保护作用。NAD对这些肾脏损害的预防作用可能是通过其抗氧化和抗炎作用实现的。
Introduction. Nephrotoxicity is one of the important side effects of anthracycline antibiotics. The aim of this study was to investigate the effects of nicotinamide (NAD), an antioxidant agent, against nephrotoxicity induced by doxorubicin (DXR). Methods. The rats were divided into control, NAD alone, doxorubicin (20 mg/kg, i.p.) and DXR plus NAD (200 mg/kg, i.p.) groups. At the end of the 10th day, kidney tissues were removed for light microscopy and analysis. The level of tissues' catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), inducible nitric oxide (iNOS) and endothelial nitric oxide (eNOS) activities were determined. Results. The activities of CAT, GPx, and GSH were decreased, and Po was increased in renal tissue of doxorubicin group compared with other groups. The tissue of the doxorubicin group showed some histopathological changes such as glomerular vacuolization and degeneration, adhesion to Bowman's capsule and thickening and untidiness of tubular and glomerular capillary basement membranes. Histopathological examination showed that NAD prevented partly DXR-induced tubular and glomerular damage. Conclusions. Pretreatment with NAD protected renal tissues against DXR-induced nephrotoxicity. Preventive effects of NAD on these renal lesions may be via its antioxidant and anti-inflammatory action.