Alruhaimi Reem S, Hassanein Emad H M, Ahmeda Ahmad F, Alnasser Sulaiman M, Atwa Ahmed M, Sabry Mostafa, Alzoghaibi Mohammed A, Mahmoud Ayman M
Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University-Assiut Branch, Assiut 71524, Egypt.
Tissue Cell. 2024 Dec;91:102576. doi: 10.1016/j.tice.2024.102576. Epub 2024 Sep 27.
Heavy metals are toxic environmental pollutants with serious health effects on humans and animals. Cadmium (Cd) is known for its serious nephrotoxic effect and its toxicity involves oxidative stress (OS) and inflammation. Diallyl disulfide (DADS), a main constituent of garlic, exhibites cytoprotective and antioxidant activities. This study investigated the effect of DADS on OS, inflammation, and fibrosis induced by Cd in rat kidney, pointing to the involvement of transforming growth factor-β (TGF-β)/Smad3 and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling, and peroxisome proliferator-activated receptor gamma (PPARγ). Rats received DADS for 14 days and Cd on day 7 and blood and kidney samples were collected. Cd elevated serum creatinine, urea and uric acid, provoked kidney histopathological alterations and collagen deposition, increased kidney malondialdehyde (MDA) level, and decreased glutathione (GSH) and antioxidant enzymes. Nuclear factor-kappaB (NF-κB) p65, interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β, and CD68 were upregulated in Cd-administered rat kidney. DADS prevented kidney injury, mitigated OS, suppressed NF-κB, CD68 and pro-inflammatory mediators, and boosted antioxidants. DADS downregulated TGF-β1, Smad3 phosphorylation and Kelch-like ECH-associated protein-1 (Keap1), and increased Nrf2, HO-1, cytoglobin, and PPARγ. In conclusion, DADS protects the kidney against Cd toxicity by attenuating OS, inflammation, and TGF-β1/Smad3 signaling, and enhancement of Nrf2/HO-1 signaling, antioxidants, and PPARγ.
重金属是有毒的环境污染物，对人类和动物的健康有严重影响。镉（Cd）以其严重的肾毒性作用而闻名，其毒性涉及氧化应激（OS）和炎症。二烯丙基二硫醚（DADS）是大蒜的主要成分之一，具有细胞保护和抗氧化活性。本研究调查了DADS对Cd诱导的大鼠肾脏OS、炎症和纤维化的影响，指出转化生长因子-β（TGF-β）/Smad3和核因子红细胞2相关因子2（Nrf2）/血红素加氧酶-1（HO-1）信号通路以及过氧化物酶体增殖物激活受体γ（PPARγ）的参与。大鼠接受DADS处理14天，在第7天给予Cd，然后采集血液和肾脏样本。Cd升高了血清肌酐、尿素和尿酸水平，引发了肾脏组织病理学改变和胶原蛋白沉积，增加了肾脏丙二醛（MDA）水平，并降低了谷胱甘肽（GSH）和抗氧化酶水平。在给予Cd的大鼠肾脏中，核因子-κB（NF-κB）p65、白细胞介素（IL）-6、肿瘤坏死因子（TNF）-α、IL-1β和CD68上调。DADS预防了肾脏损伤，减轻了OS，抑制了NF-κB、CD68和促炎介质，并增强了抗氧化剂。DADS下调了TGF-β1、Smad3磷酸化和 Kelch样ECH相关蛋白-1（Keap1），并增加了Nrf2、HO-1、细胞红蛋白和PPARγ。总之，DADS通过减轻OS、炎症和TGF-β1/Smad3信号通路，增强Nrf2/HO-1信号通路、抗氧化剂和PPARγ来保护肾脏免受Cd毒性的影响。
