No abstract

No abstract

Myocardial fibrosis in offspring with hyperglycemia is confirmed first; supplementation with zinc, selenium, and chromium to GDM mothers suppresses these changes in offspring.

Previous studies have reported that microcystin-LR (MC-LR) levels are highly correlated with abnormal renal function indicators, suggesting that MC-LR is an independent risk factor for kidney damage. However, the evidence for the exact regulation mechanism of MC-LR on kidney damage is still limited, and further in-depth exploration is needed. In addition, the mitochondria-related mechanism of MC-LR leading to kidney damage has not been elucidated. To this end, the present study aimed to further explore the mechanism of mitophagy related to kidney damage induced by MC-LR through in vitro and in vivo experiments. Male C57BL/6 mice were fed with a standard rodent pellet and exposed daily to MC-LR (20 μg/kg·bw) via intraperitoneal injections for 7 days. Moreover, HEK 293 cells were treated with MC-LR (20 μM) for 24 h. The histopathological results exhibited kidney damage after MC-LR exposure, characterized by structurally damaged nephrotomies, with inflammatory cell infiltration. Similarly, a significant increase in renal interstitial fibrosis was observed in the kidneys of MC-LR-treated mice compared with those of the control group (CT) mice. MC-LR exposure caused impaired kidney function, with markedly increased blood urea nitrogen (BUN), creatinine (Cr), and uric acid (UA) levels in mice. Ultrastructural analysis exhibited obviously swollen, broken, and disappearing mitochondrial crests, and partial mitochondrial vacuoles in the MC-LR-treated HEK 293 cells. The Western blotting results demonstrated that exposure to MC-LR significantly increased the protein expressions of MKK6, p-p38, and p62, while the expression of mitophagy-related proteins was significantly inhibited in the kidneys of mice and HEK293 cells, including parkin, TOM20, and LC3-II, indicating the inhibition of mitophagy. Therefore, our data suggest that the inhibition of MKK6-mediated mitophagy might be the toxicological mechanism of kidney toxicity in mice with acute exposure to MC-LR.

No abstract

No abstract

Objectives Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and results in adverse outcomes for pregnant women and their offspring. Endoplasmic reticulum (ER) stress is associated with insulin resistance and implicates in the development of GDM. Zinc, selenium and chromium have been shown to maintain glucose homeostasis via multiple mechanisms, but how these trace elements affect the insulin resistance and ER stress in GDM are largely unknown. Methods A GDM rat model was induced by feeding female Sprague-Dawley (SD) rats a high-fat (45%) and sucrose (HFS) diet, while zinc (10 mg/kg.bw), selenium (20 ug/kg.bw), chromium (20 ug/kg.bw) were daily supplemented alone or in combination from 6 weeks before mating to the end of lactation period. Maternal metabolic parameters, hepatic ER stress and insulin signaling were analyzed. Results The results showed that zinc, selenium and chromium supplementation dramatically alleviated HFS-induced glucose intolerance and oxidative stress during entire experiment period. Hepatic ER stress as well as the unfolded protein response (UPR) was activated in GDM rats, characterized by the up-regulation of glucose-regulated protein 78 (GRP78), phosphorylated the protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), and the inositol-requiring enzyme 1α (p-IRE1α). Zinc, selenium and chromium supplementation significantly prevented this activation, by which contributes to the promotion of the phosphorylated protein kinase B (p-AKT) related insulin signaling and maintenance of glucose homeostasis. Conclusions Zinc, selenium and chromium supplementation may be a promising way to prevent the development of GDM by alleviating hepatic ER stress. Funding Sources This work was financially supported by the Angel Nutritech Nutrition Fund (AF2017003) and the National Natural Science Foundation of China (NSFC, 81373006 and 81973043).