Antagonistic effect of selenium on programmed necrosis of testicular Leydig cells caused by cadmium through endoplasmic reticulum stress in chicken.

Cadmium (Cd) is a widely distributed environmental contaminant that is highly toxic to animals and humans. However, detailed reports on Cd-induced programmed necrosis have not been seen in chicken testicular Leydig cells. Selenium (Se) is a trace element in the human body that has cytoprotective effects in a variety of pathological damages caused by heavy metals. This study investigated the potential mechanisms of Cd-induced programmed cell necrosis and the antagonistic effect of Se on Cd toxicity. Chicken testis Leydig cells were divided into six groups, namely, control, Se (5 µmol/L Na2SeO3), Cd (20 µmol/L CdCl2), Se + Cd (5 µmol/L Na2SeO3 and 20 µmol/L CdCl2), 4-phenylbutyric acid (4-PBA) + Cd (10 mmol/L 4-phenylbutyric acid and 20 µmol/L CdCl2), and Necrostatin-1 (Nec-1) + Cd (60 µmol/L Necrostatin-1 and 20 µmol/L CdCl2). The results showed that Cd exposure decreased the activity of CAT, GSH-Px, and SOD and the concentration of GSH, and increased the concentration of MDA and the content of ROS. Relative mRNA and protein expression of GRP78, PERK, ATF6, IRE1, CHOP, and JNK increased in the Cd group, and mRNA and protein expression of TNF-α, TNFR1, RIP1, RIP3, MLKL, and PARP1 significantly increased in the Cd group, while Caspase-8 mRNA and protein expression significantly decreased. The abnormal expression of endoplasmic reticulum stress-related proteins was significantly reduced by 4-PBA pretreatment; the increased expression of TNF-α, TNFR1, RIP1, RIP3, MLKL, and PARP1 caused by Cd toxicity was alleviated; and the expression of caspase-8 was upregulated. Conversely, the increased mRNA and protein expression of endoplasmic reticulum stress marker genes (GRP78, ATF6, PERK, IRE1, CHOP, JNK) caused by Cd was not affected after pretreatment with Nec-1. We also found that these Cd-induced changes were significantly attenuated in the Se + Cd group. We clarified that Cd can cause programmed necrosis of chicken testicular Leydig cells through endoplasmic reticulum stress, and Se can antagonize Cd-induced programmed necrosis of chicken testicular Leydig cells.

Selenium alleviates cadmium-induced oxidative stress, endoplasmic reticulum stress and programmed necrosis in chicken testes.

Cadmium (Cd) is a common heavy metal pollutant, and one of the important target organs of its toxicity is the testis. Selenium (Se) has the ability to antagonize the toxicity of Cd. However, the mechanism of the alleviating effects of Se on Cd in chicken testis injury through oxidative stress, endoplasmic reticulum stress (ERS), and programmed necrosis remained unclear. To explore this, 80 7-day-old chickens were divided into the Control group, the Se group (1.00 mg/kg Se), the Cd group (150.00 mg/kg Cd), and the CdSe group. On the 30th and 60th days, serum and chicken testis tissue samples were collected for testing. The results showed that Cd exposure resulted in swelling and deformation of seminiferous tubules, and thinning of the seminiferous epithelium. The ROS and MDA increased, and the SOD, CAT, GSH, GSH-Px decreased. The expression of GRP78, PERK, IRE1, ATF6, CHOP, and JNK in the Cd group increased. The expression of TNF-α, TNFR1, RIP1, RIP3, MLKL, and PARP1 increased, while the expression of Caspase-8 decreased. Histopathological changes, oxidative stress, ERS, and programmed necrosis were improved after CdSe treatment. In conclusion, Se antagonized the toxicity of Cd, and Se could alleviate Cd-induced oxidative stress, ERS, and programmed necrosis in chicken testis.

Selenium-Alleviated Testicular Toxicity by Modulating Inflammation, Heat Shock Response, and Autophagy Under Oxidative Stress in Lead-Treated Chickens.

Lead (Pb), a toxic pollutant, is toxic to the testis. However, biological events during testicular Pb poisoning were not well understood. Selenium (Se) has the ability to antagonize Pb toxicity. The purpose of this research was to clarify the relief mechanism of Se on testicular toxicity of Pb from the perspective of oxidative stress, inflammation, heat shock response, and autophagy in a chicken model. Sixty male Hyline chickens (7-day-old) were randomly assigned into four groups. The feeding program consisted of a commercial diet, a Se-supplemented diet (1 mg kg-1 Se), a Pb-supplemented diet (350 mg L-1 Pb), and a Se- and Pb-supplemented diet, respectively. On the 12th week, serums were collected to measure testosterone level and testes were removed to determine testis weight, histological structure, Pb and Se concentrations, oxidative stress indicators, and mRNA and protein expression of inflammatory cytokines, heat shock proteins, and autophagy-related genes. The results showed that Pb poisoning changed the histological structure of testes; decreased serum testosterone level, testis weight, catalase, glutathione-s-transferase, and total antioxidative capacity activities; increased hydrogen peroxide content; inhibited interleukin (IL)-2 and mammalian target of rapamycin expression; and promoted IL-4, IL-12ß, heat shock proteins, Beclin 1, Dynein, autophagy-related proteins 5, light chain 3 (LC3)-I, and LC3-II expression in the testes of chickens. Se intervention mitigated the aforementioned alterations induced by Pb. In conclusion, Pb led to oxidative stress, which triggered inflammation, heat shock response, and autophagy. Se administration mitigated testicular toxicity of Pb mainly by mitigating oxidative stress in male chickens.