Cadmium (Cd) is a common environmental pollutant and occupational toxicant that seriously affects various mammalian organs, especially the kidney. Iron ion is an essential trace element in the body, and the disorder of iron metabolism is involved in the development of multiple pathological processes. An iron overload can induce a new type of cell death, defined as ferroptosis. However, whether iron metabolism is abnormal in Cd-induced nephrotoxicity and the role of ferroptosis in Cd-induced nephrotoxicity need to be further elucidated. Sprague Dawley male rats were randomly assigned into three groups: a control group, a 50 mg/L CdCl2-treated group, and a 75 mg/L CdCl2-treated group by drinking water for 1 month and 6 months, respectively. The results showed that Cd could induce renal histopathological abnormalities and dysfunction, disrupt the mitochondria’s ultrastructure, and increase the ROS and MDA content. Next, Cd exposure caused GSH/GPX4 axis blockade, increased FTH1 and COX2 expression, decreased ACSL4 expression, and significantly decreased the iron content in proximal tubular cells or kidney tissues. Further study showed that the expression of iron absorption-related genes SLC11A2, CUBN, LRP2, SLC39A14, and SLC39A8 decreased in proximal tubular cells or kidneys after Cd exposure, while TFRC and iron export-related gene SLC40A1 did not change significantly. Moreover, Cd exposure increased SLC11A2 gene expression and decreased SLC40A1 gene expression in the duodenum. Finally, NAC or Fer-1 partially alleviated Cd-induced proximal tubular cell damage, while DFO and Erastin further aggravated Cd-induced cell damage. In conclusion, our results indicated that Cd could cause iron deficiency and chronic kidney injury by interfering with the iron metabolism rather than typical ferroptosis. Our findings suggest that an abnormal iron metabolism may contribute to Cd-induced nephrotoxicity, providing a novel approach to preventing kidney disease in clinical practice.

Japanese quail is a highly economically valuable bird due to its commercial production for meat and eggs. Although studies have reported Cadmium (Cd) is a ubiquitous heavy metal that can cause injury to various organs, the molecular mechanisms of Cd on quail kidney injury remain largely unknown. It has been reported that Honokiol (HKL), a highly functional antioxidant, can protect cells against oxidative stress effectively. This study was conducted to investigate the effects of Cd on quail kidneys injury and the protective effect of HKL on Cd-induced nephrotoxicity. A total of 40 Japanese quails were randomly divided into four groups: the control group, Cd treatment group, Co-treatment group and HKL treatment group. The results showed that Cd resulted in significant changes in growth performance, kidney histopathology and kidney biochemical status, antioxidant enzymes and oxidative stress parameters, and ultrastructure of renal tubular epithelial cells, compared with controls. Cd increased the expression of autophagy-related and apoptosis-related genes, but decreased expression of lysosomal function-related and UPR^mt-related genes. The co-treatment group ameliorated Cd-induced nephrotoxicity by alleviating oxidative stress, inhibiting apoptosis, repairing autophagy dysfunction and UPR^mt disorder. In conclusion, dietary supplementation of HKL showed beneficial effects on Japanese quail kidney injury caused by Cd.

Heavy metal pollution is a problem that cannot be ignored. Due to the prevalence of cadmium in the environment and its harmful effects on humans, cadmium pollution has become a research hotspot recently. The mechanism of cadmium-induced toxicity has also drawn much attention and most studies have been conducted using whole cells, but the toxicological mechanism of cadmium remains unclear. In this study, we aimed to obtain NRK-52E cells at different growth stages by various methods and analyze the differences in cadmium toxicity. The results show that the cadmium sensitivity of cells in each phase was different and the late apoptotic rate was increased significantly after 5 µM Cd treatment. In addition, cadmium easily induces apoptosis of G0- and S-phase cells, as well as necrosis of S- and M-phase cells, but has no significant effect on G1-phase cells. Overall, we first explored the differences in the effects of cadmium on NRK-52E cells at various growth phases. Besides, the findings of this study might provide a theoretical basis for further exploration of the toxicological mechanism of cadmium.Abbreviations Cd: cadmium; CDK: cyclin-dependent kinases; DAPI 2-(4-amidinophenyl)-1H-indole-6-carboxamidine; TBST: Tris-buffered saline with Tween-20; PI: propidium iodide; DMEM: Dulbecco’s Modified Eagle Medium; BCA: bicinchoninic acid

Glandular stomach plays a crucial role in the digestive system and overall physiological functions of chickens. Mycotoxins, including deoxynivalenol (DON), in contaminated feed damage the immune and digestive systems of chickens and hinder their growth. However, the mechanism underlying DON toxicity on glandular stomach inflammation remains unclear. This study found that DON induced inflammation and injury in the glandular stomach of chicken embryos by regulating pyroptosis and autophagy. DON stimulated proinflammatory factor release, activated NLRP3 inflammasome and its downstream elements, increased caspase-3 and GSDME expression to mediate pyroptosis and injury, and inhibited autophagy in glandular stomach by decreasing ATG5, ATG7, and Beclin-1 expressions and increasing mTOR expression. Besides, DON reduced LC3-II/LC3-I ratio and elevated p62 expression. These results confirmed the association between DON-induced pyroptosis and autophagy inhibition, providing key evidence for understanding DON toxicity and mitigating DON contamination in poultry farming; nevertheless, the underlying mechanism must be further elucidated.

Cadmium (Cd) has adverse effects on organisms. Serine is an essential nutritional factor and its nutritional value is extremely high for body. To explore the effects of serine on spleen toxicity induced by Cd in mice, cadmium chloride (CdCl₂, 50 mg/L) and serine (50 g/L) were individually administered or co-administrated in drinking water of mice for 18 weeks. Results demonstrated that Cd exposure induced splenic toxicity and serine against the toxicity damage caused by Cd in mice. Under Cd stress, trace element homeostasis was disturbed, the mice's body weight and spleen index were increased, and splenic morphology and ultrastructure were altered. Furthermore, Cd exposure led to the cell populations disorder, which in turn triggers cell death. Notably, Cd treatment induced oxidative stress and inflammation, increased M1/M2 (iNOS, CD68) and Th1/Th2 (T-bet, CD4) levels, decreased M1/M2 (Arg1) and Th1/Th2 (GATA3) levels, while disrupted the macrophages and lymphocytes homeostasis, which trigged apoptosis and pyroptosis in spleen. In contrast, serine supplementation changed the levels of Cd and other elements, weakened Cd-induced tissue damage and inflammation, enhanced antioxidant capacity, significantly restored cell homeostasis, and effectively inhibited Cd-induced apoptosis and pyroptosis in the spleen. Shortly, the results verified that serine had an ameliorating toxicity effect and restored the M1/M2 and Th1/Th2 balance, restrained apoptosis and pyroptosis induced by Cd.

Selenium-enriched Saccharomyces cerevisiae (SSC) as organic selenium (Se) has been shown to have better advantages and is approved for use in animal feed rather than inorganic Se, however, there is little available data on the toxic effects of SSC on poultry. The present study was conducted to investigate the effects of high-dose SSC on growth performance, antioxidant status, tissue fat content and Se concentration, and selenoenzyme mRNA expression in chicks. A total of 500, 1-day-old SPF chicks were randomly divided into 5 groups with 10 replicates of 10 chicks each. Group 1 served as a control and was fed a basal diet supplemented with 0.15 mg/kg Se from sodium selenite (SS), group 2 was fed the basic diet supplemented with 1.5 mg/kg Se from SS, while groups 3, 4, and 5 were fed the basal diet supplemented with 1.5, 5 and 10 mg/kg Se from SSC, respectively. The results showed that SS and SSC supplementation significantly affected the average daily feed intake (ADFI), feed/gain ratio (FCR), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities, total antioxidant capacity (T-AOC), malondialdehyde (MDA) content, tissue fat content and Se concentration, and GPx1 and GPx4 mRNA levels compared with the control group (P < 0.05). Compared with group 2, group 3 exhibited higher GPx and SOD activities, tissue Se concentration, and lower MDA content on d 30, and higher Se concentration, GPx1 mRNA levels in liver and breast muscle and GPx4 mRNA levels in liver and thigh muscle, and lower MDA content on d 60 (P < 0.05). The results of correlation analysis showed that high-dose SSC supplementation was positively correlated with AFDI, FCR, MDA content, and tissue Se concentration, and negatively correlated with GPx and SOD activities, T-AOC, GPx1 and GPx4 mRNA levels in tissues. In conclusion, up to 1.5 mg/kg Se from SSC in diet may be a safe concentration for chicks that exhibited better biological effects than SS, the toxic effects of high-dose SSC supplementation mainly exhibited growth decrease, peroxidation and lipid metabolism disturbance, and became stronger with the increase of dietary Se levels.