Punicalagin protects against the development of pancreatic injury and insulitis in rats with induced T1DM by reducing inflammation and oxidative stress.

Pancreatic inflammation and oxidative damage remain major concerns in type 1 diabetes mellitus (T1DM). Punicalagin, a major polyphenol in pomegranates, exhibited antioxidant and protective effects on several organs in case of T1DM; however, no study has yet explored the protective effects of punicalagin on the pancreas and islets of Langerhans. T1DM was induced by injecting 40 mg/kg streptozotocin (STZ) intraperitoneally. Punicalagin (1 mg/kg ip) was injected daily for 15 days after T1DM induction. In diabetic rats, punicalagin treatment lowered the levels of inflammatory biomarkers (monocyte chemoattractant protein-1 and C-reactive protein) and adhesion molecules (E-selectin, intercellular adhesion molecule, and vascular cell adhesion molecule) while activating myeloperoxidase activity. Treatment of diabetic rats with punicalagin improved glutathione content and superoxide dismutase, catalase, and glutathione peroxidase activities; upregulated serum paraoxonase-1 activity; and prevented the elevation lipid peroxidation and protein oxidation products in the pancreas. Furthermore, punicalagin protected the pancreas against STZ-induced histopathological alterations and increased immune-reactive ß-cells while reducing leucocyte infiltration into the islets of Langerhans, leading to normalized blood glucose and insulin levels. These findings indicated that punicalagin might protect against the development of insulitis in T1DM. In conclusion, punicalagin exerts a strong protective effect on the pancreas against oxidative injury and inflammation in STZ-induced experimental T1DM. The present results recommend punicalagin as a potential adjuvant for reducing diabetes-associated insulitis.

Melatonin controlled apoptosis and protected the testes and sperm quality against bisphenol A-induced oxidative toxicity.

Epidemiological reports have indicated a correlation between the increasing bisphenol A (BPA) levels in the environment and the incidence of male infertility. In this study, the protective effects of melatonin on BPA-induced oxidative stress and apoptosis were investigated in the rat testes and epididymal sperm. Melatonin (10 mg/kg body weight (bw)) was injected concurrently with BPA (50 mg/kg bw) for 3 and 6 weeks. The administration of BPA significantly increased oxidative stress in the testes and epididymal sperm. This was associated with a decrease in the serum testosterone level as well as sperm quality, chromatin condensation/de-condensation level, and the percentage of haploid germ cells in the semen. BPA administration caused a significant increase in apoptosis accompanied by a decrease in the expression of the antiapoptotic proteins Bcl-2 in the testes and epididymal sperm. The concurrent administration of melatonin decreased oxidative stress by modulating the levels of glutathione, superoxide dismutase, and catalase as well as the malondialdehyde and hydrogen peroxide concentrations in the testes and sperm. Melatonin sustained Bcl-2 expression and controlled apoptosis. Furthermore, melatonin maintained the testosterone levels, ameliorated histopathological changes, increased the percentages of seminal haploid germ cells, and protected sperm chromatin condensation process, indicating appropriate spermatogenesis with production of functional sperm. In conclusion, melatonin protected against BPA-induced apoptosis by controlling Bcl-2 expression and ameliorating oxidative stress in the testes and sperm. Thus, melatonin is a promising pharmacological agent for preventing the potential reproductive toxicity of BPA following occupational or environmental exposures.