Hassanein Emad H M, Alotaibi Mohammed F, Alruhaimi Reem S, Abd El-Ghafar Omnia A M, Mohammad Mostafa K, Atwa Ahmed M, Mahmoud Ayman M
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University-Assiut Branch, Assiut 71524, Egypt.
Physiology Department, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia.
J Trace Elem Med Biol. 2024 Dec;86:127560. doi: 10.1016/j.jtemb.2024.127560. Epub 2024 Nov 12.
Cadmium (Cd) is a heavy metal environmental pollutant that can cause serious health problems. Cd can cause structural changes in the testes and exposure to this heavy metal is associated with the loss of sperms and male infertility. The role of oxidative stress and inflammation in Cd toxicity has been acknowledged. Diallyl disulfide (DADS), an organo-sulfur compound found in garlic, possesses antioxidant, anti-inflammatory, and cytoprotective effects. This study evaluated the protective effect of DADS against Cd reproductive toxicity in male rats, emphasizing the involvement of redox imbalance, TLR-4/NF-κB and JAK1/STAT3 signaling, and SIRT1.
DADS (10 mg/kg body weight) was administered orally to rats for 14 days and a single dose of Cd (1.2 mg/kg) was injected intraperitoneally on day 7. Blood and samples from the testes were collected for analysis.
Cd caused testicular injury manifested by multiple histopathological changes and loss of sperms from seminiferous tubules. Circulating levels of gonadotropins and testosterone were decreased in Cd-administered rats. DADS prevented Cd-induced testicular injury and ameliorated serum levels of gonadotropins and testosterone. Cd increased testicular reactive oxygen species (ROS) and malondialdehyde (MDA) and upregulated TLR-4, NF-κB, pro-inflammatory cytokines, JAK1 and STAT3 phosphorylation, Bax and caspase-3, while decreased antioxidants and Bcl-2. DADS effectively decreased ROS and MDA, downregulated TLR-4, NF-κB, JAK1, STAT3, pro-inflammatory cytokines and pro-apoptosis markers in Cd-administered rats. In addition, DADS enhanced antioxidants, Bcl-2, SIRT1 and cytoglobin in the testis of Cd-administered rats.
DADS prevents Cd-induced testicular injury by attenuating oxidative stress, apoptosis, and TLR-4/NF-κB and JAK1/STAT3 signaling, and upregulating SIRT1 and antioxidants.
镉（Cd）是一种重金属环境污染物，可导致严重的健康问题。镉可引起睾丸结构变化，接触这种重金属与精子丢失和男性不育有关。氧化应激和炎症在镉毒性中的作用已得到认可。二烯丙基二硫化物（DADS）是大蒜中的一种有机硫化合物，具有抗氧化、抗炎和细胞保护作用。本研究评估了DADS对雄性大鼠镉生殖毒性的保护作用，重点关注氧化还原失衡、TLR-4/NF-κB和JAK1/STAT3信号通路以及SIRT1的参与情况。
将DADS（10毫克/千克体重）口服给予大鼠14天，并在第7天腹腔注射单剂量的镉（1.2毫克/千克）。采集血液和睾丸样本进行分析。
镉导致睾丸损伤，表现为多种组织病理学变化以及生精小管中精子丢失。给予镉的大鼠循环中的促性腺激素和睾酮水平降低。DADS预防了镉诱导的睾丸损伤，并改善了促性腺激素和睾酮的血清水平。镉增加了睾丸中的活性氧（ROS）和丙二醛（MDA），并上调了TLR-4、NF-κB、促炎细胞因子、JAK1和STAT3的磷酸化、Bax和半胱天冬酶-3，同时降低了抗氧化剂和Bcl-2。DADS有效降低了给予镉的大鼠中的ROS和MDA，下调了TLR-4、NF-κB、JAK1、STAT3、促炎细胞因子和促凋亡标志物。此外，DADS增强了给予镉的大鼠睾丸中的抗氧化剂、Bcl-2、SIRT1和细胞珠蛋白。
DADS通过减轻氧化应激、细胞凋亡以及TLR-4/NF-κB和JAK1/STAT3信号通路，并上调SIRT1和抗氧化剂来预防镉诱导的睾丸损伤。
