Txnrd3 knockout enhancement of lung injury induced by Ni exposure via the VEGF-VEGFR-2 axis and alleviation of this effect by melatonin.

Ni exposure leads to respiratory diseases in mice. Txnrd3 has been shown to have a protective effect on the body, but there is a paucity of empirical research focusing specifically on lung tissue. Melatonin possesses potent antioxidant, anti-inflammatory, and anti-fibrotic effects. By regulating inflammation-related factors, melatonin can activate the VEGF signaling pathway, ultimately alleviating lung injuries caused by Ni exposure. One hundred and sixty 8-week-old C57BL/6N mice, that were wild-type or Txnrd3-/- mice and 25-30 g in weight, were randomly divided into eight groups, including the NC group, Ni group, melatonin-treated group, and Ni plus melatonin group. Ni (10 mg/kg) was gavaged, and melatonin (2 mg/kg) was administered for 21 days. Inflammatory cells were found in the bronchioles of Txnrd3-/- mice under Ni exposure. Ultrastructural examination revealed that the homozygous-Ni group had a high amount of collagen fibers. The antioxidant capacity studies also revealed that mice lungs underwent oxidative stress. The results of qRT-PCR and WB showed that Ni induced an inflammatory response, which was also aggravated in Txnrd3-/- mice. Melatonin can effectively reduce the above symptoms. In conclusion, Ni causes lung injury by activating the VEGF-VEGFR-2 pathway and Txnrd3 knockout aggravates injury after Ni exposure.

Role of selenoprotein M knockdown in the melatonin antagonism of nickel-induced apoptosis and endoplasmic reticulum stress in mouse heart. / 硒蛋白Mæ•²é™¤åœ¨è¤ªé»‘ç´ æ‹®æŠ—é•è¯±å¯¼çš„å°é¼ å¿ƒè„ç»†èƒžå‡‹äº¡å’Œå† è´¨ç½‘åº”æ¿€ä¸­çš„ä½œç”¨.

The aim of this study was to investigate the role of selenoprotein M (SelM) in endoplasmic reticulum stress and apoptosis in nickel-exposed mouse hearts and to explore the detoxifying effects of melatonin. At 21 d after intraperitoneal injection of nickel chloride (NiCl2) and/or melatonin into male wild-type (WT) and SelM knockout (KO) C57BL/6J mice, NiCl2 was found to induce changes in the microstructure and ultrastructure of the hearts of both WT and SelM KO mice, which were caused by oxidative stress, endoplasmic reticulum stress, and apoptosis, as evidenced by decreases in malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) activity. Changes in the messenger RNA (mRNA) and protein expression of genes related to endoplasmic reticulum stress (activating transcription factor 4 (ATF4), inositol-requiring protein 1 (IRE1), c-Jun N-terminal kinase (JNK), and C/EBP homologous protein (CHOP)) and apoptosis (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, Caspase-9, and Caspase-12) were also observed. Notably, the observed damage was worse in SelM KO mice. Furthermore, melatonin alleviated the heart injury caused by NiCl2 in WT mice but could not exert a good protective effect in the heart of SelM KO mice. Overall, the findings suggested that the antioxidant capacity of SelM, as well as its modulation of endoplasmic reticulum stress and apoptosis, plays important roles in nickel-induced heart injury.

The role of selenoprotein M in nickel-induced pyroptosis in mice spleen tissue via oxidative stress.

Nickel (Ni) is a heavy metal element and a pollutant that threatens the organism's health. Melatonin (Mel) is an antioxidant substance that can be secreted by the organism and has a protective effect against heavy metals. Selenoprotein M (SelM) is a selenoprotein widely distributed of the body, and its role is to protect these tissues from oxidative damage. To study the mechanism of Ni, Mel, and SelM in mouse spleen, 80 SelM+/+ wild-type and 80 SelM-/- homozygous mice were divided into 8 groups with 20 mice in each group. The Ni group was intragastric at a concentration of 10 mg/kg, while the Mel group was intragastric at 2 mg/kg. Mice were injected with 0.1 mL/10 g body weight for 21 days. Histopathological and ultrastructural observations showed the changes in Ni, such as the destruction of white and red pulp and the appearance of pyroptosomes. SelM knockout showed more severe injury, while Mel could effectively interfere with Ni-induced spleen toxicity. The results of antioxidant capacity determination showed that Ni could cause oxidative stress in the spleen, and Mel could also effectively reduce oxidative stress. Finally, Ni exposure increased the expression levels of the pyroptotic genes, including apoptosis-associated speck protein (ASC), absent in melanoma-2 (AIM2), NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), Caspase-1, interleukin- (IL-) 18, and IL-1ß (p < 0.05). Loss of SelM significantly increased these (p < 0.05), while Mel decreased the alleviated impact of Ni. In conclusion, the loss of SelM aggravated Ni-induced pyroptosis of the spleen via activating oxidative stress, which was alleviated by Mel, but the effect of Mel was not obvious in the absence of SelM, which reflected the important role of SelM in Ni-induced pyroptosis.

Decreased thioredoxin reductase 3 expression promotes nickel-induced damage to cardiac tissue via activating oxidative stress-induced apoptosis and inflammation.

Thioredoxin reductase 3 (Txnrd3) plays a crucial role in antioxidant and anti-cancer activities, and sperm maturation. The damage of heavy metals, including Nickel (Ni), is the most prominent harm in social development, and hampering Txnrd3 might exacerbate Ni-induced cardiac damage. In this study, a total of 160 8-week-old C57BL/N male mice with 25-30 g weight of Txnrd3+/+ wild-type and Txnrd3-/- homozygote-type were randomly divided into eight groups. The mice in the control and Ni groups were gavaged with distilled water and a freshly prepared 10 mg/kg NiCl2 solution. Melatonin (Mel) groups were administered at a concentration of 2 mg/kg for 21 days at the mice's 0.1 ml/10 g body weight. Ni exposure up-regulated the messenger RNA (mRNA) levels of mitochondrial apoptosis (caspase-3, caspase-9, cytochrome c, p53, and BAX), autophagy (LC3, ATG 1, ATG 7, and Beclin-1), and inflammation (TNF-α, COX 2, IL-1ß, IL-2, IL-6, and IL-7)-related markers, but down-regulated the mRNA levels of BCL-2, p62 and mTOR (p < .05). Ni exposure decreased the expression of BCL-2 and p62 protein but increased the expression levels of caspase-3, caspase-9, cytochrome c, p53, BAX, ATG 7, Beclin-1, TNF-α, COX 2, IL-1ß and IL-2 protein (p < .05). Ni increased the contents of glutathione disulfide (GSSG) and malondialdehyde (MDA) and decreased the activities of catalase (CAT) and total superoxide dismutase (T-SOD) (p < .05). Decreased Txnrd3 expression significantly exacerbated changes compared to the Ni exposure (p < .05). Mel significantly attenuated these changes, but the effect decreased when Txnrd3 was inhibited (p < .05). In conclusion, decreased Txnrd3 expression promoted Ni-induced mitochondrial apoptosis and inflammation via oxidative stress and aggravated heart damage in mice. Decreased Txnrd3 expression significantly reduced the protective effect of Mel to Ni exposure.

Astilbin attenuates apoptosis induced by cadmium through oxidative stress in carp (Cyprinus carpio L.) head kidney lymphocyte.

As a kind of environmental pollutant, heavy metal Cadmium (Cd) exists widely in the environment. It is well known that Cd can accumulate and cause damage in liver, kidney and other organs. However, there are few studies on the immune cytotoxicity of Cd to fish. In particular, there are few studies on the toxicity of Cd to the head kidney lymphocytes of common carp. In order to further explore these mechanisms, we established an Cd exposure model in vitro. At the same time, we used the natural antioxidant astilbin (AST) to treat the cells to study its antagonistic effect on the toxicity of Cd. After exposure to Cd, the level of oxidative stress in head kidney lymphocytes increased, and the mRNA and protein expression of apoptosis-related markers Fas, FADD, Caspase8 and Caspase3 increased significantly (P < 0.05), which led to lymphocytes apoptosis. Hoechst staining and AO/EB staining also showed that the level of apoptosis increased after exposure to Cd. This is consistent with our previous research results. AST treatment reduced oxidative stress and apoptosis induced by Cd. In addition, oxidative stress inhibitor NAC could also reduce head kidney lymphocytes apoptosis induced by Cd, indicating that oxidative stress was involved in this process. Our results suggested that AST can alleviate the apoptosis of carp head kidney lymphocytes induced by Cd through oxidative stress. This study enriches the theoretical mechanism of Cd toxicity to fish head kidney lymphocytes, and puts forward a method to solve the toxicity of Cd, which provides a theoretical and research basis for the in vivo study of animal models in the future.