The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Cardamonin exerts a protective effect against autophagy and apoptosis in the testicles of diabetic male rats through the expression of Nrf2 via p62-mediated Keap-1 degradation

  • Samir, Shereen M. (Department of Medical Physiology, College of Medicine, Mansoura University) ;
  • Elalfy, Mahmoud (Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Mansoura University) ;
  • El Nashar, Eman Mohamad (Department of Anatomy, Faculty of Medicine, King Khalid University) ;
  • Alghamdi, Mansour A. (Department of Anatomy, College of Medicine, King Khalid University) ;
  • Hamza, Eman (Medical Biochemistry Department, College of Medicine, Mansoura University) ;
  • Serria, Mohamed Saad (Medical Biochemistry Department, College of Medicine, Mansoura University) ;
  • Elhadidy, Mona G. (Department of Medical Physiology, College of Medicine, Mansoura University)
  • Received : 2020.12.24
  • Accepted : 2021.05.27
  • Published : 2021.07.01
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Abstract

Cardamonin (CARD) is a chalconoid with anti-inflammatory and antioxidant properties, and it is present in several plants. We sought to explore whether CARD exerts any positive effects against hyperglycemia-induced testicular dysfunction caused by type 2 diabetes and aimed to identify its possible intracellular pathways. Adult male rats were subdivided into six groups: control, CARD, diabetic (DM), DM + glibenclamide (GLIB), DM + CARD and DM + GLIB + CARD. Type 2 DM induced a significant increase in blood glucose and insulin resistance, along with diminished serum insulin, testosterone and gonadotropins levels, which were associated with the impairment of key testicular androgenic enzymes and cellular redox balance. Administration of CARD at a dose of 80 mg/kg for 4 weeks effectively normalized all of these alterations, and the improvement was confirmed by epididymal sperm analysis. After treatment with CARD, the pathological changes in spermatogenic tubules were markedly improved. Significantly, CARD upregulated testicular glucose transporter-8 (GLUT-8) expression and had inhibitory effects on elevated autophagy markers and caspase-3 immunoreactive cells. Furthermore, our results revealed that CARD was able to attenuate damage via activation of Nrf2 through the p62-dependent degradation of testicular anti-Kelch-like ECH-associated protein-1 (Keap-1). In conclusion, this study suggests that CARD provides protection against diabetic stress-mediated testicular damage. The use of CARD with conventional anti-diabetic therapy was associated with improved efficacy compared with conventional therapy alone.

Keywords

Acknowledgement

The authors would like to extend their appreciation to the Deanship of Scientific Research at King Khalid University, Saudi Arabia, for funding this project through the research group program under grant number (R.G.P.1/217/41). The Medical Physiology Department and Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Egypt, are acknowledged for their contribution to the experimental part of the present study. The authors would also like to express their gratitude to King Khalid University, Saudi Arabia, for providing administrative and technical support.

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