Melatonin is a well-documented hormone that plays central roles in the regulation of sleep-wake cycles. There is cumulative evidence to suggest that melatonin is also a pleiotropic regulator of inflammation, and luzindole has been widely used as a melatonin receptor antagonist. This study investigated the potential effects of luzindole on LPS/d-galactosamine (d-GalN)-induced acute hepatitis. The results indicated that treatment with luzindole alleviated histological damage in the liver, reduced the level of transaminases in plasma and improved the survival of LPS/d-GalN-exposed mice. Treatment with luzindole also suppressed the production of the pro-inflammatory cytokines TNF-α and IL-6 in LPS/d-GalN-exposed mice. In addition, treatment with luzindole inhibited the activation of caspase-3, -8 and -9, and suppressed the cleavage of caspase-3 and poly(ADP-ribose) polymerase. Therefore, treatment with luzindole attenuates LPS/d-GalN-induced acute liver injury, suggesting that luzindole might have potential value for the intervention of inflammation-based hepatic disorders.

中文翻译：

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Luzindole可减轻LPS / d-半乳糖胺诱发的小鼠急性肝炎。

褪黑激素是一种有据可查的激素，在调节睡眠-觉醒周期中起着核心作用。有累积的证据表明褪黑激素还是炎症的多效性调节剂，鲁辛多尔已被广泛用作褪黑激素受体拮抗剂。这项研究调查了luzindole对LPS / d-半乳糖胺（d-GalN）诱导的急性肝炎的潜在影响。结果表明，用鲁辛多治疗可减轻肝脏的组织学损伤，降低血浆中转氨酶的水平，并改善了LPS / d-GalN暴露小鼠的存活率。在含有LPS / d-GalN的小鼠中，用luzindole进行的治疗还抑制了促炎性细胞因子TNF-α和IL-6的产生。此外，用luzindole处理可抑制caspase-3，-8和-9的激活，并抑制caspase-3和聚（ADP-核糖）聚合酶的切割。因此，用luzindole治疗可减轻LPS / d-GalN诱导的急性肝损伤，这表明luzindole可能对干预基于炎症的肝病具有潜在价值。