Diabetes-induced testicular oxidative stress, inflammation, and caspase-dependent apoptosis: the protective role of metformin

Arch Physiol Biochem. 2020 Dec;126(5):377-388. doi: 10.1080/13813455.2018.1543329. Epub 2018 Dec 4.

Abstract

Context: Metformin's effect on glycaemic control is well documented, but its effect on diabetes-induced testicular impairment has been scarcely reported.Objective: To investigate the effects of metformin on testicular oxidative stress, inflammation, and apoptosis, which largely contribute to fertility decline in diabetic state.Methods: Male Sprague-Dawley rats were divided into 3 groups (n = 6/group) namely: normal control (NC), diabetic control (DC), and metformin (300 mg/kg b.w./d)-treated diabetic groups. Metformin was administrated for 4 weeks.Results: Decreased mRNA expressions and activities of antioxidant enzymes were seen in the testes of DC group. mRNA and protein expressions of pro-inflammatory and pro-apoptotic markers increased, while interleukin-10 and proliferating cell nuclear antigen (PCNA) decreased in the testes of DC group. Treatment with metformin up-regulated antioxidant enzymes, down-regulated inflammation, and apoptosis and increased PCNA immunoexpression in the testes.Conclusions: Metformin protects the testes from diabetes-induced impairment and may improve male reproductive health in diabetic state.

Keywords: Diabetes mellitus; apoptosis; inflammation; metformin; oxidative stress.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Diabetes Mellitus, Experimental / complications*
  • Hypoglycemic Agents / pharmacology*
  • Inflammation / drug therapy*
  • Inflammation / etiology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Interleukin-10 / metabolism
  • Male
  • Metformin / pharmacology*
  • Oxidative Stress / drug effects*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Hypoglycemic Agents
  • Proliferating Cell Nuclear Antigen
  • Protective Agents
  • Interleukin-10
  • Metformin