Protective effect of sitagliptin and whole-body γ-irradiation in diabetes-induced cardiac injury

Can J Physiol Pharmacol. 2021 Jun;99(6):676-684. doi: 10.1139/cjpp-2020-0454. Epub 2020 Oct 27.

Abstract

Diabetes mellitus is associated with an increased risk of cardiac complications; this study aimed to investigate effect of sitagliptin (SITA) alone or combined with γ-irradiation on diabetes-associated cardiac injury. Rats were treated with SITA (100 mg/kg per day; p.o.) for 2 weeks followed by a single dose of whole-body γ-irradiation (3 Gy). Solitary administration of SITA or combined treatment with γ-irradiation succeeded to ameliorate the increase in serum levels of glucose, total cholesterol, triglycerides, creatine kinase-MB, and malondialdehyde, coupled by increased insulin and reduced glutathione levels. Their cardioprotective potential was confirmed through attenuating the apoptotic signaling by mitigating Bcl-2-associated X protein, caspase-3, and apoptosis-inducing factor expression, while augmenting the anti-apoptotic factors, B cell lymphoma-2 (Bcl-2), and heat shock protein 70 (HSP-70) in left ventricular tissue homogenates. These findings were supported histopathologically. In conclusion, treatment with SITA alone or combined with γ-irradiation may prove beneficial in diabetes-accompanied cardiac insult. This could be due to the crosstalk between the antioxidant, anti-apoptotic, and restoration of body's defense capacities.

Keywords: HSP-70; apoptose; apoptosis; diabetes; diabète; oxidative stress; protéine de choc thermique 70; rayons γ; sitagliptin; sitagliptine; stress oxydatif; γ-irradiation.

MeSH terms

  • Animals
  • Antioxidants
  • Apoptosis / drug effects
  • Gamma Rays
  • Glutathione / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects
  • Rats
  • Sitagliptin Phosphate*

Substances

  • Antioxidants
  • Malondialdehyde
  • Glutathione
  • Sitagliptin Phosphate