Fazal Yumna, Fatima Syeda Nuzhat, Shahid Syed Muhammad, Mahboob Tabassum
Department of Biochemistry, University of Karachi, Karachi, Pakistan.
The Karachi Institute of Biotechnology & Genetic Engineering (KIBGE), University of Karachi, Karachi, Pakistan
J Renin Angiotensin Aldosterone Syst. 2015 Dec;16(4):1046-51. doi: 10.1177/1470320314545777. Epub 2014 Aug 20.
This study aimed to evaluate the protective effects of curcumin on angiotensin-converting enzyme (ACE) gene expression, oxidative stress and anti-oxidant status in thioacetamide (TAA)-induced hepatotoxicity in rats.
Total 32 albino Wistar rats (male, 200-250 g) were divided into six groups (n=8). Group 1: untreated controls; Group 2: received TAA (200 mg/kg body weight (b.w.); i.p.) for 12 weeks; Group 3: received curcumin (75 mg/kg b.w.) for 24 weeks; Group 4: received TAA (200 mg/kg b.w.; i.p.) for 12 weeks+curcumin (75 mg/kg b.w.) for 12 weeks.
A significantly higher ACE gene expression was observed in TAA-induced groups as compared with control, indicating more synthesis of ACE proteins. Treatment with curcumin suppressed ACE expression in TAA liver and reversed the toxicity produced. TAA treatment results in higher lipid peroxidation and lower GSH, SOD and CAT than the normal, and this produces oxidative stress in the liver. Cirrhotic conditions were confirmed by serum enzymes (ALT, AST and ALP) as well as histopathological observations.
Curcumin treatment reduced oxidative stress in animals by scavenging reactive oxygen species, protecting the anti-oxidant enzymes from being denatured and reducing the oxidative stress marker lipid peroxidation. Curcumin treatment restores hepatocytes, damaged by TAA, and protects liver tissue approaching cirrhosis.
本研究旨在评估姜黄素对硫代乙酰胺(TAA)诱导的大鼠肝毒性中血管紧张素转换酶(ACE)基因表达、氧化应激和抗氧化状态的保护作用。
总共32只白化Wistar大鼠(雄性,体重200 - 250克)被分为六组(每组n = 8)。第1组:未处理的对照组;第2组:接受TAA(200毫克/千克体重;腹腔注射),持续12周;第3组:接受姜黄素(75毫克/千克体重),持续24周;第4组:接受TAA(200毫克/千克体重;腹腔注射)12周 + 姜黄素(75毫克/千克体重)12周。
与对照组相比,在TAA诱导组中观察到ACE基因表达显著更高,表明ACE蛋白合成更多。用姜黄素处理可抑制TAA肝脏中的ACE表达并逆转所产生的毒性。与正常情况相比,TAA处理导致更高的脂质过氧化以及更低的谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT),这在肝脏中产生氧化应激。通过血清酶(谷丙转氨酶、谷草转氨酶和碱性磷酸酶)以及组织病理学观察证实了肝硬化情况。
姜黄素处理通过清除活性氧、保护抗氧化酶不被变性以及降低氧化应激标志物脂质过氧化来降低动物体内的氧化应激。姜黄素处理可恢复被TAA损伤的肝细胞,并保护接近肝硬化的肝组织。