College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China.
Food Chem Toxicol. 2013 Mar;53:1-9. doi: 10.1016/j.fct.2012.11.001. Epub 2012 Nov 28.
The study investigated the protective effects of carnosic acid (CA), the principal constituent of rosemary, on lipopolysaccharide (LPS)-induced oxidative/nitrosative stress and hepatotoxicity in rats. CA was administered orally to rats at doses of 15, 30 and 60 mg/kg body weight before LPS challenge (single intraperitoneal injection, 1 mg/kg body weight). The results revealed that CA inhibited LPS-induced liver damage and disorder of lipid metabolism, which were mainly evidenced by decreased serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. CA also inhibited LPS-induced oxidative/nitrosative stress by decreasing lipid peroxidation, protein carbonylation, and serum levels of nitric oxide. Histopathological examination demonstrated that CA could improve pathological abnormalities and reduce the immigration of inflammatory cells in liver tissues with LPS challenge. Concurrently, CA potently inhibited the LPS-induced rise in serum levels of the pro-inflammatory cytokines tumor necrosis factor-α and interleukin-6. CA supplementation markedly enhanced the body's cellular antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and glutathione in serum and liver after the LPS challenge. In conclusion, the present study suggests that CA successfully and dose dependently attenuates LPS-induced hepatotoxicity possibly by preventing cytotoxic effects of oxygen free radicals, NO and cytokines.
本研究旨在探讨迷迭香酸（CA）对脂多糖（LPS）诱导的大鼠氧化/硝化应激和肝毒性的保护作用。CA 通过灌胃方式给予 LPS 攻击前的大鼠，剂量分别为 15、30 和 60mg/kg 体重（单次腹腔注射，1mg/kg 体重）。结果表明，CA 抑制了 LPS 诱导的肝损伤和脂质代谢紊乱，这主要表现在血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶和碱性磷酸酶水平的降低。CA 还通过降低脂质过氧化、蛋白质羰基化和血清一氧化氮水平来抑制 LPS 诱导的氧化/硝化应激。组织病理学检查表明，CA 可以改善 LPS 攻击引起的肝脏组织病理性异常和减少炎症细胞浸润。同时，CA 可显著抑制 LPS 诱导的促炎细胞因子肿瘤坏死因子-α和白细胞介素-6 水平的升高。CA 补充剂通过恢复 LPS 攻击后血清和肝脏中超氧化物歧化酶、谷胱甘肽过氧化物酶和谷胱甘肽的水平，显著增强了机体的细胞抗氧化防御系统。综上所述，本研究表明 CA 成功地、剂量依赖性地减轻了 LPS 诱导的肝毒性，可能是通过防止氧自由基、NO 和细胞因子的细胞毒性作用。
