Ameliorating Immune-dependent Inflammation and Apoptosis by Targeting TLR4/MYD88/NF-ᵰ5B Pathway by Celastrol Mitigates the Diabetic Reproductive Dysfunction.

Abstract

This study aimed to examine the protective effect of celastrol on testicular dysfunction in diabetic rats and the potential underlying mechanisms. All rats included in the study were divided into four groups: a control group treated with sodium citrate buffer and vehicle), a celastrol-treated control group, a streptozotocin (STZ)-induced diabetic group following insulin resistance, and a celastrol-treated diabetic group. Serum glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, interleukin (IL)-1β, tumor necrosis factor-alpha, and testosterone levels were measured. In addition, the levels of testicular homogenate superoxide dismutase and malondialdehyde were assessed. Furthermore, testicular tissue relative TLR4, NF-ᵰ5B, and MYD88 expression were quantitatively measured using polymerase chain reaction. Histopathological and immunohistochemical studies were also conducted. The results revealed that treatment with celastrol significantly reduced TLR4, MyD88, NF-ᵰ5B expressions and the levels of inflammatory mediators such as tumor necrosis factor-alpha and IL-1ᵯD in the testicular tissue of treated rats. These findings suggest has the potential to be effective in the treatment of diabetes-induced testicular injury by inhibiting testicular inflammation, apoptosis, and oxidative stress.