Ghosh Ayantika, Sil Parames C
Department of Chemistry, Bose Institute 93/1, Acharya Prafulla Chandra Road, Kolkata-700009, India.
J Biochem Mol Biol. 2007 Nov 30;40(6):1039-49. doi: 10.5483/bmbrep.2007.40.6.1039.
Overdoses of acetaminophen cause hepato-renal oxidative stress. The present study was undertaken to investigate the protective effect of a 43 kDa protein isolated from the herb Cajanus indicus, against acetaminophen-induced hepatic and renal toxicity. Male albino mice were treated with the protein for 4 days (intraperitoneally, 2 mg/kg body wt) prior or post to oral administration of acetaminophen (300 mg/kg body wt) for 2 days. Levels of different marker enzymes (namely, glutamate pyruvate transaminase and alkaline phosphatase), creatinine and blood urea nitrogen were measured in the experimental sera. Intracellular reactive oxygen species production and total antioxidant activity were also determined from acetaminophen and protein treated hepatocytes. Indices of different antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione-S-transferase) as well as lipid peroxidation end-products and glutathione were determined in both liver and kidney homogenates. In addition, Cytochrome P450 activity was also measured from liver microsomes. Finally, histopathological studies were performed from liver sections of control, acetaminophen-treated and protein pre- and post-treated (along with acetaminophen) mice. Administration of acetaminophen increased all the serum markers and creatinine levels in mice sera along with the enhancement of hepatic and renal lipid peroxidation. Besides, application of acetaminophen to hepatocytes increased reactive oxygen species production and reduced the total antioxidant activity of the treated hepatocytes. It also reduced the levels of antioxidant enzymes and cellular reserves of glutathione in liver and kidney. In addition, acetaminophen enhanced the cytochrome P450 activity of liver microsomes. Treatment with the protein significantly reversed these changes to almost normal. Apart from these, histopathological changes also revealed the protective nature of the protein against acetaminophen induced necrotic damage of the liver tissues. Results suggest that the protein protects hepatic and renal tissues against oxidative damages and could be used as an effective protector against acetaminophen induced hepato-nephrotoxicity.
对乙酰氨基酚过量会导致肝肾氧化应激。本研究旨在探讨从草药木豆中分离出的一种43 kDa蛋白质对乙酰氨基酚诱导的肝毒性和肾毒性的保护作用。雄性白化小鼠在口服乙酰氨基酚（300 mg/kg体重）2天之前或之后，接受该蛋白质治疗4天（腹腔注射，2 mg/kg体重）。检测实验血清中不同标记酶（即谷氨酸丙酮酸转氨酶和碱性磷酸酶）、肌酐和血尿素氮的水平。还从乙酰氨基酚和蛋白质处理的肝细胞中测定细胞内活性氧的产生和总抗氧化活性。测定肝和肾匀浆中不同抗氧化酶（即超氧化物歧化酶、过氧化氢酶、谷胱甘肽-S-转移酶）的指标以及脂质过氧化终产物和谷胱甘肽的含量。此外，还从肝微粒体中测量细胞色素P450活性。最后，对对照组、乙酰氨基酚处理组以及蛋白质预处理和后处理（与乙酰氨基酚一起）组小鼠的肝脏切片进行组织病理学研究。给予乙酰氨基酚会增加小鼠血清中所有血清标志物和肌酐水平，同时增强肝脏和肾脏的脂质过氧化。此外，将乙酰氨基酚应用于肝细胞会增加活性氧的产生，并降低处理后肝细胞的总抗氧化活性。它还降低了肝脏和肾脏中抗氧化酶的水平以及谷胱甘肽的细胞储备。此外，乙酰氨基酚增强了肝微粒体的细胞色素P450活性。用该蛋白质治疗可显著将这些变化逆转至几乎正常水平。除此之外，组织病理学变化也显示了该蛋白质对乙酰氨基酚诱导的肝组织坏死损伤的保护作用。结果表明，该蛋白质可保护肝和肾组织免受氧化损伤，并可作为对抗乙酰氨基酚诱导的肝肾毒性的有效保护剂。
