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首页> 外文期刊>Drug Design, Development and Therapy >Suppression of Cisplatin-Induced Hepatic Injury in Rats Through Alarmin High-Mobility Group Box-1 Pathway by Ganoderma lucidum : Theoretical and Experimental Study
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Suppression of Cisplatin-Induced Hepatic Injury in Rats Through Alarmin High-Mobility Group Box-1 Pathway by Ganoderma lucidum : Theoretical and Experimental Study

机译：通过Ganoderma lucidum的Alarm High-Mobility Group Box-1途径抑制大鼠大鼠的肝损伤：理论和实验研究

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Purpose: Drug-induced liver injury (DILI) is the most common cause of acute liver failure. The aim of this study was to investigate the molecular mechanisms by which Ganoderma lucidum mushroom (GLM) may ameliorate cisplatin (CP)-induced hepatotoxicity theoretically and experimentally. Materials and Methods: Thirty-six male Sprague-Dawley (SD) rats were divided into six groups, two of them are normal and Ganoderma lucidum control groups. Liver injury was induced by a single dose of CP (12 mg/kg i.p) in four groups, one of them is CP control group. Besides cisplatin injection in day 1, rats in groups (4– 6) were subjected to GLM (500 mg/kg/day) either every other day or daily oral dose or via i.p injection for 10 consecutive days. Results: In this study, GLM supplementation caused significant reduction of elevated high-mobility group box-1 (HMGB-1) with a concurrent decline in TNF-α and upregulation of IL-10 compared to the CP group (P 0.05). The histopathological and fibrosis evaluation significantly confirmed the improvement upon simultaneous treatment with GLM. Moreover, immunohistochemical examination also confirmed the recovery following GLM treatment indicated by downregulation of NF-κB, p53 and caspase-3 along with upsurge of B-cell lymphoma 2 (Bcl-2) expression (P 0.05). GLM treatment significantly decreased serum levels of hepatic injury markers; ALT, AST, T. bilirubin as well as oxidative stress markers; MDA and Hsub2/subOsub2/sub with a concomitant increase in hepatic GSH and SOD. Also, the performed docking simulation of ganoderic acid exhibited good fitting and binding with HMGB-1 through hydrogen bond formation with conservative amino acids which gives a strong evidence for its hepatoprotective effect and may interpret the effect of Ganoderma lucidum . Conclusion: GLM attenuated hepatic injury through downregulation of HMGB-1/NF-kB and caspase-3 resulted in modulation of the induced oxidative stress and the subsequent cross-talk between the inflammatory and apoptotic cascade indicating its promising role in DILI.
机译：目的：药物诱导的肝损伤（DILI）是急性肝衰竭最常见的原因。本研究的目的是研究灵芝蘑菇（GLM）可以改善顺铂（CP）诱导肝毒性的分子机制，理论上和实验诱导肝毒性。材料和方法：三十六只雄性Sprague-Dawley（SD）大鼠分为6组，其中两组是正常的和灵芝对照组。通过四组中的单剂量CP（12mg / kg i.p）诱导肝损伤，其中一组是Cp对照组。除了第1天中的顺铂注射外，将大鼠（4-6）进行GLM（500mg / kg /天），每隔一天或每日口服剂量或通过I.p注射连续10天。结果：在本研究中，GLM补充导致升高的高迁移率组箱-1（HMGB-1）的显着降低了TNF-α的同时下降，与CP组相比，IL-10的上调（P <0.05）。组织病理学和纤维化评估显着证实了对GLM同时治疗的改善。此外，免疫组织化学检查还证实了通过NF-κB，p53和Caspase-3的下调和B细胞淋巴瘤2（Bcl-2）表达的高度调节所示的GLM处理后的回收率（P <0.05）。 GLM治疗显着降低了血清血清损伤标志物水平; ALT，AST，T. Bilirubin以及氧化应激标记物; MDA和H 2 O 2 ，肝gsh和sod的伴随增加。而且，通过具有保守氨基酸的氢键形成表现出与HMGB-1的氢键形成良好的拟合和结合，这对其肝脏保护作用产生了强有力的证据，并可解释灵霉菌的作用。结论：GLM通过HMGB-1 / NF-KB和Caspase-3的下调减毒肝损伤导致诱导氧化应激和随后炎症和凋亡级联之间的随后串扰，表明其在DILI中有希望的作用。

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