Apoptosis in pancreatic β-cells is induced by arsenic and atorvastatin in Wistar rats with diabetes mellitus type 2

J Trace Elem Med Biol. 2018 Mar:46:144-149. doi: 10.1016/j.jtemb.2017.12.008. Epub 2017 Dec 23.

Abstract

Introduction: Diabetes Mellitus type 2 (T2D) is a multifactorial disease. However, it is known that there is an important effect in pancreatic β-cells caused by apoptosis of pro-apoptotic proteins, possibly related to arsenic exposure and atorvastatin treatment.

Objective: The goal of this study was to evaluate the effects of atorvastatin treatment on apoptosis of pancreatic β-cells in Wistar rats with induced diabetes type 2 exposed to arsenic.

Material & methods: T2D in Wistar rats was induced by administration of Streptozotocin. The plasmatic glucose concentrations were measured using the glucose oxidase method, and the concentration of glycated hemoglobin (HbA1c) in whole blood was determined. Exposure to arsenic was measured from urine using atomic absorption with hydride generation, and pro-apoptotic proteins in pancreatic β-cells were observed using the Western blotting technique.

Results: Caspase-3 was present in rats that were treated with 10 mg/kg of oral atorvastatin and exposed to 0.01 and 0.025 mg/L of arsenic, but no others proteins were present, such as pro Caspase-8, bcl-2, and Fas. The glycemic levels were 129.2 ± 7.0 mg/dL in the control group and 161.8 ± 14.6 mg/dL and 198.3 ± 18.2 mg/dL (p < .05) in the study groups. HbA1c increased from 2.53% to 3.64% (p < .05) in the control and study groups.

Conclusions: Atorvastatin treatment and arsenic exposure alone are capable of generating apoptosis in pancreatic β-cells of Wistar rats with T2D. Together, all of these factors induce apoptosis in pancreatic cells.

Keywords: Apoptosis; Arsenic exposure; Atorvastatin treatment; Diabetes mellitus type 2.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Apoptosis / drug effects*
  • Arsenic / toxicity*
  • Atorvastatin / toxicity*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / pathology*
  • Diabetes Mellitus, Type 2 / chemically induced
  • Diabetes Mellitus, Type 2 / pathology*
  • Female
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / toxicity*
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / pathology
  • Male
  • Rats, Inbred WKY
  • Streptozocin

Substances

  • Antioxidants
  • Blood Glucose
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Streptozocin
  • Atorvastatin
  • Arsenic