Abstract

Context

Rosmarinic acid (RA) dose-dependently ameliorates acetaminophen (APAP) induced hepatotoxicity in rats. However, whether RA hepatoprotective effect is by regulating RACK1 and its downstream signals is still unclear.

Objective

This study explores the RA protective effect on APAP-induced ALI and its mechanism.

Materials and methods

Sixty Kunming mice 6–8 weeks old were randomly separated into six groups (n = 10) and pre-treated with normal saline, ammonium glycyrrhetate (AG) or RA (10, 20 or 40 mg/kg i.p./day) for two consecutive weeks. Then, APAP (300 mg/kg, i.g.) was administrated to induce ALI, except for the control. Serum alanine/aspartate aminotransferases (ALT and AST), malondialdehyde (MDA), superoxide dismutase (SOD) and histopathology were used to authenticate RA effect. The liver RACK1 and TNF-α were measured by western blot.

Results

Compared with the APAP group, different dosages RA significantly decreased ALT (52.09 ± 7.98, 55.13 ± 10.19, 65.08 ± 27.61 U/L, p < 0.05), AST (114.78 ± 19.87, 115.29 ± 31.91, 101.78 ± 21.85 U/L, p < 0.05), MDA (2.37 ± 0.87, 2.13 ± 0.87, 1.86 ± 0.39 nmol/mg, p < 0.01) and increased SOD (306.178 ± 90.80, 459.21 ± 58.54, 444.01 ± 78.09 U/mg, p < 0.05). With increasing doses of RA, RACK1 and TNF-α expression decreased. Moreover, the RACK1 and TNF-α levels were positively correlated with MDA (r = 0.8453 and r = 0.9391, p < 0.01).

Discussion and conclusions

Our findings support RA as a hepatoprotective agent to improve APAP-induced ALI and the antioxidant effect mediated through RACK1/TNF-α pathway.

中文翻译：

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迷迭香酸通过 RACK1/TNF-α 介导的抗氧化作用改善对乙酰氨基酚诱导的小鼠急性肝损伤

摘要

语境

迷迭香酸 (RA) 剂量依赖性地改善对乙酰氨基酚 (APAP) 诱导的大鼠肝毒性。然而，RA的保肝作用是否是通过调节RACK1及其下游信号尚不清楚。

客观的

本研究探讨RA对APAP诱导的ALI的保护作用及其机制。

材料和方法

将 60 只 6-8 周龄的昆明小鼠随机分成 6 组（n  = 10），并用生理盐水、甘草次酸铵 (AG) 或 RA（10、20 或 40 mg/kg ip/天）连续两次预处理周。然后，给予APAP（300 mg/kg，ig）以诱导ALI，除了对照。血清丙氨酸/天冬氨酸氨基转移酶 (ALT 和 AST)、丙二醛 (MDA)、超氧化物歧化酶 (SOD) 和组织病理学用于验证 RA 效应。通过蛋白质印迹测量肝脏RACK1和TNF-α。

结果

与APAP组相比，不同剂量RA显着降低ALT（52.09±7.98、55.13±10.19、65.08±27.61 U/L，p  < 0.05）、AST（114.78±19.87、115.29±31.91、101.78±21.85 U/L，p  < 0.05)、MDA (2.37 ± 0.87, 2.13 ± 0.87, 1.86 ± 0.39 nmol/mg, p  < 0.01) 和增加的 SOD (306.178 ± 90.80, 459.21 ± 58.54, 444.01 ± 78.09 U/mg, p  < 0.05)。随着 RA 剂量的增加，RACK1 和 TNF-α 的表达下降。此外，RACK1 和 TNF-α 水平与 MDA 呈正相关（r  = 0.8453 和r  = 0.9391，p  < 0.01）。

讨论和结论

我们的研究结果支持 RA 作为一种肝脏保护剂来改善 APAP 诱导的 ALI 和通过 RACK1/TNF-α 途径介导的抗氧化作用。