Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, 11671 Riyadh, Saudi Arabia.
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University-Assiut Branch, 71524 Assiut, Egypt.
Front Biosci (Landmark Ed). 2024 Oct 23;29(10):369. doi: 10.31083/j.fbl2910369.
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.
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.
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) ( < 0.001), upregulated toll-like receptor (TLR)-4, nuclear factor-kappaB (NF-κB), pro-inflammatory mediators, and caspase-3 ( < 0.001) whereas decreased glutathione (GSH) and antioxidant enzymes ( < 0.001). Cd downregulated peroxisome proliferator activated receptor gamma (PPARγ), a transcription factor involved in inflammation and OS suppression ( < 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.
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).
重金属会导致严重的健康问题，影响不同的器官。镉（Cd）是一种环境污染物，已知其对不同器官具有毒理学后果。氧化应激（OS）和炎症在镉暴露引起的肝毒性中起着核心作用。二烯丙基二硫（DADS），一种存在于大蒜中的有机硫化合物，以其细胞保护和抗氧化作用而闻名。在这项研究中，研究了 DADS 对镉诱导的炎症、氧化应激和肝损伤的影响。
通过口服灌胃补充 DADS14 天，在第 7 天给大鼠腹腔内单次注射 1.2mg/kg 体重的 Cd。实验结束时采集血液和肝脏样本进行分析。
Cd 给药导致明显的肝功能障碍、退行性变化、坏死、炎症细胞浸润、胶原沉积和其他组织病理学改变。Cd 增加了肝丙二醛（MDA）和一氧化氮（NO）（<0.001），上调了 Toll 样受体（TLR）-4、核因子-kappaB（NF-κB）、促炎介质和 caspase-3（<0.001），同时降低了谷胱甘肽（GSH）和抗氧化酶（<0.001）。Cd 下调了过氧化物酶体增殖物激活受体γ（PPARγ），一种参与炎症和 OS 抑制的转录因子（<0.001）。DADS 改善了肝损伤和组织改变，减轻了 OS 和细胞凋亡，抑制了 TLR-4/NF-κB 信号通路，并增强了抗氧化剂。此外，DADS 上调了 Cd 给药大鼠肝脏中的 PPARγ。
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。DADS 可能对保护接触 Cd 的个体的肝脏有价值，但需要进一步研究阐明其他潜在机制。
