Diallyl Disulfide Mitigates Cadmium Hepatotoxicity by Attenuating Oxidative Stress and TLR-4/NF-κB Signaling and Upregulating PPARγ.

IF 3.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Frontiers in bioscience (Landmark edition) Pub Date : 2024-10-23 DOI:10.31083/j.fbl2910369
Reem S Alruhaimi, Emad H M Hassanein, Mohammed F Alotaibi, Mohammed A Alzoghaibi, Omnia A M Abd El-Ghafar, Mostafa K Mohammad, Sulaiman M Alnasser, Ayman M Mahmoud
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Abstract

Background: Heavy metals can cause serious health problems that affect different organs. Cadmium (Cd) is an environmental contaminant known for its toxicological consequences on different organs. Hepatotoxicity is a serious effect of exposure to Cd with oxidative stress (OS) and inflammation playing a central role. Diallyl disulfide (DADS), an organo-sulfur compound found in garlic, is known for its cytoprotective and antioxidant effects. In this study, the effect of DADS on Cd-induced inflammation, oxidative stress and liver injury was investigated.

Methods: DADS was supplemented for 14 days via oral gavage, and a single intraperitoneal dose of Cd (1.2 mg/kg body weight) was administered to rats on day 7. Blood and liver samples were collected at the end of the experiment for analyses.

Results: Cd administration resulted in remarkable hepatic dysfunction, degenerative changes, necrosis, infiltration of inflammatory cells, collagen deposition and other histopathological alterations. Cd increased liver malondialdehyde (MDA) and nitric oxide (NO) (p < 0.001), upregulated toll-like receptor (TLR)-4, nuclear factor-kappaB (NF-κB), pro-inflammatory mediators, and caspase-3 (p < 0.001) whereas decreased glutathione (GSH) and antioxidant enzymes (p < 0.001). Cd downregulated peroxisome proliferator activated receptor gamma (PPARγ), a transcription factor involved in inflammation and OS suppression (p < 0.001). DADS ameliorated liver injury and tissue alterations, attenuated OS and apoptosis, suppressed TLR-4/NF-κB signaling, and enhanced antioxidants. In addition, DADS upregulated PPARγ in the liver of Cd-administered rats.

Conclusions: DADS is effective against Cd-induced hepatotoxicity and its beneficial effects are linked to suppression of inflammation, OS and apoptosis and upregulation of PPARγ. DADS could be valuable to protect the liver in individuals at risk of Cd exposure, pending further studies to elucidate other underlying mechanism(s).

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二烯丙基二硫化物通过减轻氧化应激和 TLR-4/NF-κB 信号以及上调 PPARγ 减轻镉的肝毒性
背景:重金属会对不同器官造成严重的健康问题。镉(Cd)是一种环境污染物,因其对不同器官的毒性后果而闻名。肝毒性是接触镉后的一个严重后果,其中氧化应激(OS)和炎症起着核心作用。大蒜中的有机硫化合物二烯丙基二硫化物(DADS)具有细胞保护和抗氧化作用。本研究调查了 DADS 对镉诱导的炎症、氧化应激和肝损伤的影响:方法:大鼠口服 DADS 14 天,第 7 天腹腔注射单剂量镉(1.2 毫克/千克体重)。实验结束时收集血液和肝脏样本进行分析:结果:给大鼠服用镉会导致肝功能明显失调、变性、坏死、炎症细胞浸润、胶原沉积和其他组织病理学改变。镉增加了肝脏丙二醛(MDA)和一氧化氮(NO)(p < 0.001),上调了toll样受体(TLR)-4、核因子-kappaB(NF-κB)、促炎介质和caspase-3(p < 0.001),同时降低了谷胱甘肽(GSH)和抗氧化酶(p < 0.001)。镉会下调过氧化物酶体增殖激活受体γ(PPARγ),这是一种参与炎症和OS抑制的转录因子(p < 0.001)。DADS可改善肝损伤和组织改变,减轻OS和细胞凋亡,抑制TLR-4/NF-κB信号传导,并增强抗氧化能力。此外,DADS 还能上调 Cd 给药大鼠肝脏中的 PPARγ :结论:DADS 对镉诱导的肝毒性有效,其有益作用与抑制炎症、OS 和细胞凋亡以及上调 PPARγ 有关。在进一步研究阐明其他潜在机制之前,DADS 对保护镉暴露风险个体的肝脏可能很有价值。
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