Mohan Iyyapu Krishna, Khan Mahmood, Shobha Jagdish Chandra, Naidu Madireddy Umamaheswara Rao, Prayag Aruna, Kuppusamy Periannan, Kutala Vijay Kumar
Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, 500 082, Hyderabad, India.
Cancer Chemother Pharmacol. 2006 Dec;58(6):802-8. doi: 10.1007/s00280-006-0231-8. Epub 2006 Mar 22.
Cisplatin (CP)-induced nephrotoxicity is associated with the increased generation of reactive oxygen metabolites and lipid peroxidation in kidney, caused by the decreased levels of antioxidants and antioxidant enzymes. The purpose of this study was to evaluate the role of Spirulina, blue-green alga with antioxidant properties, in the protection of cisplatin-induced nephrotoxicity in rat.
Rats were treated with CP (6 mg/kg bw, single dose, intraperitoneally). Spirulina (1,000 mg/kg) was administered orally for 8 days and CP treatment was given on day 4. Nephrotoxicity was assessed, 6 days after the CP treatment, by measuring plasma urea, creatinine, urinary N-acetyl-(D-glucose-aminidase) (beta-NAG) and histopathology of kidney.
Rats treated with CP showed marked nephrotoxicity as evidenced from the significant elevation in plasma urea, creatinine and urinary beta-NAG. Histological assessment revealed marked proximal tubular necrosis and extensive epithelial vacuolization in the kidney of CP-treated rats. Superoxide dismutase, catalase and glutathione peroxidase were decreased and lipid peroxidation was increased in kidney tissue. Pretreatment with Spirulina protected the rats from CP-induced nephrotoxicity. The rise in plasma urea, creatinine, urinary beta-NAG, plasma and kidney tissue MDA and histomorphological changes were significantly attenuated by Spirulina. In vitro studies using human ovarian cancer cells revealed that Spirulina did not interfere with the cytotoxic effects of CP on tumor cells.
In summary, Spirulina significantly protected the CP-induced nephrotoxicity through its antioxidant properties.
顺铂(CP)诱导的肾毒性与肾脏中活性氧代谢产物生成增加及脂质过氧化有关,这是由抗氧化剂和抗氧化酶水平降低所致。本研究的目的是评估具有抗氧化特性的蓝绿藻螺旋藻在保护大鼠免受顺铂诱导的肾毒性方面的作用。
大鼠腹腔注射CP(6 mg/kg体重,单剂量)。螺旋藻(1000 mg/kg)口服给药8天,在第4天给予CP治疗。在CP治疗后6天,通过测量血浆尿素、肌酐、尿N-乙酰-(D-葡萄糖胺酶)(β-NAG)和肾脏组织病理学评估肾毒性。
用CP治疗的大鼠表现出明显的肾毒性,血浆尿素、肌酐和尿β-NAG显著升高证明了这一点。组织学评估显示,CP治疗的大鼠肾脏中近端肾小管明显坏死,上皮细胞广泛空泡化。肾脏组织中超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶减少,脂质过氧化增加。螺旋藻预处理可保护大鼠免受CP诱导的肾毒性。螺旋藻显著减轻了血浆尿素、肌酐、尿β-NAG、血浆和肾脏组织丙二醛的升高以及组织形态学变化。使用人卵巢癌细胞的体外研究表明,螺旋藻不干扰CP对肿瘤细胞的细胞毒性作用。
总之,螺旋藻通过其抗氧化特性显著保护了CP诱导的肾毒性。