Nouri Ali, Heidarian Esfandiar, Nikoukar Morteza
a Student Research Committee , Shahrekord University of Medical Sciences , Shahrekord , Iran.
b Clinical Biochemistry Research Center , Basic Health Sciences Institute, Shahrekord University of Medical Sciences , Shahrekord , Iran.
Toxicol Mech Methods. 2017 Oct;27(8):561-567. doi: 10.1080/15376516.2017.1334732. Epub 2017 Jun 8.
The consumption of non-steroidal anti-inflammatory drug, such as diclofenac, can lead to hepatotoxicity. In the present study, protective effect of N-acetyl cysteine (NAC) on diclofenac-induced hepatotoxicity was investigated. Thirty-two male rats were divided into four groups. Group 1 (control group) was treated with normal saline (1 ml/kg, i.p.) for 4 d. Group 2 (test without treatment) received diclofenac only (50 mg/kg, i.p.) for 4 d. Groups 3 and 4 received diclofenac (50 mg/kg, i.p.) plus NAC (150 mg/kg, p.o) and silymarin (100 mg/kg, p.o) for 4 d, respectively. At the end of experiment, serum glutamate pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), alkaline phosphatase (ALP), lipid profile, uric acid, protein carbonyl content, MDA, liver TNF-α, ferric-reducing antioxidant power, liver catalase, superoxide dismutase, vitamin C, and histopathological examination were done. In group 2, diclofenac caused a significant increase (p < .05) in the levels of serum ALP, GOT, GPT, TNF-α, uric acid, protein carbonyl content, MDA, and liver TNF-α gene expression as opposed to group 1. In treated groups with NAC and silymarin, a significant reduction (p < .05) was seen in all above mentioned parameters as well as improved liver histopathological changes compared with group 2. This study confirmed the protective effect of NAC on diclofenac-induced hepatotoxicity in rats due to not only reduces liver inflammatory cells, TNF-α, serum MDA, and PC but also through increases liver vitamin C, catalase, and superoxide dismutase activities.
非甾体抗炎药（如双氯芬酸）的使用会导致肝毒性。在本研究中，研究了N-乙酰半胱氨酸（NAC）对双氯芬酸诱导的肝毒性的保护作用。将32只雄性大鼠分为四组。第1组（对照组）腹腔注射生理盐水（1 ml/kg），连续4天。第2组（未治疗试验组）仅腹腔注射双氯芬酸（50 mg/kg），连续4天。第3组和第4组分别腹腔注射双氯芬酸（50 mg/kg）加口服NAC（150 mg/kg）和水飞蓟宾（100 mg/kg），连续4天。实验结束时，检测血清谷丙转氨酶（GPT）、谷草转氨酶（GOT）、碱性磷酸酶（ALP）、血脂、尿酸、蛋白质羰基含量、丙二醛（MDA）、肝脏肿瘤坏死因子-α（TNF-α）、铁还原抗氧化能力、肝脏过氧化氢酶、超氧化物歧化酶、维生素C，并进行组织病理学检查。与第1组相比，第2组中双氯芬酸导致血清ALP、GOT、GPT、TNF-α、尿酸、蛋白质羰基含量、MDA水平以及肝脏TNF-α基因表达显著升高（p < 0.05）。与第2组相比，NAC和水飞蓟宾治疗组上述所有参数均显著降低（p < 0.05），且肝脏组织病理学变化有所改善。本研究证实了NAC对双氯芬酸诱导的大鼠肝毒性具有保护作用，这不仅是因为它减少了肝脏炎症细胞、TNF-α、血清MDA和蛋白质羰基，还因为它增加了肝脏维生素C、过氧化氢酶和超氧化物歧化酶的活性。
