Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Common First Year Deanship, King Saud University, Riyadh, Saudi Arabia.
Pharmacol Rep. 2020 Apr;72(2):360-367. doi: 10.1007/s43440-020-00072-8. Epub 2020 Feb 27.
Lead is a dangerous systemic toxicant and can provoke life-threatening renal injury. The plan of this study was to evaluate the potential impact of curcumin (CRMN) and L-ascorbic acid (L-ascb) alone or together to counteract lead acetate (Pb-acetate)-induced renal damage in rats and to find out the underlying mechanisms of action of these nutraceuticals.
Pb-acetate (100 mg/kg/day, i.p.) was injected in male rats along with L-ascb (250 mg/kg/day) and/or CRMN (200 mg/kg/day) orally for 7 days.
Pb-acetate administration increased serum urea, creatinine and uric acid. Renal tissue showed a marked depletion in reduced glutathione level and superoxide dismutase activity and elevation in nitric oxide and malondialdehyde levels. Serum C-reactive protein and IL-1β levels were elevated. Up-regulation of the expression of kidney injury molecule, vascular adhesion molecule-1 and Cystatin C were noticed after Pb-acetate administration. DNA fragmentation was also increased in renal tissues. Histopathological examination revealed a destructed partial layer of Bowman's capsule, proximal and distal convoluted tubules. Treatment with the aforementioned antioxidants ameliorated most of the altered measured biomarker levels.
Interestingly, the combination of L-ascb and CRMN showed the superlative protective effect against Pb-acetate-induced nephrotoxicity.
铅是一种危险的全身性毒物,可引发危及生命的肾脏损伤。本研究计划评估姜黄素(CRMN)和 L-抗坏血酸(L-ascb)单独或联合对抗醋酸铅(Pb-acetate)诱导的大鼠肾脏损伤的潜在影响,并找出这些营养保健品的作用机制。
雄性大鼠腹腔注射醋酸铅(100mg/kg/天),同时口服 L-抗坏血酸(250mg/kg/天)和/或姜黄素(200mg/kg/天),连续 7 天。
醋酸铅给药后血清尿素、肌酐和尿酸升高。肾脏组织中还原型谷胱甘肽水平和超氧化物歧化酶活性明显降低,一氧化氮和丙二醛水平升高。血清 C 反应蛋白和白细胞介素-1β水平升高。醋酸铅给药后,肾脏损伤分子、血管细胞黏附分子-1 和胱抑素 C 的表达上调。肾组织中还出现 DNA 片段化。组织病理学检查显示鲍曼氏囊的部分层遭到破坏,近端和远端曲管也受到影响。上述抗氧化剂的治疗改善了大多数改变的生物标志物水平。
有趣的是,L-抗坏血酸和姜黄素的联合使用对醋酸铅诱导的肾毒性具有最佳的保护作用。