Diabetogenic potential of dexamethasone and effect Annona muricata methanolic bark extract as post-exposure therapy in albino rats

Abstract

Diabetes mellitus (DM) is a metabolic disorder leading to high level of morbidity and mortality in human population and it has been identified as the leading cause of death from non- nfectious diseases. The use of dexamethasone has been on the increase due to widearray of therapeutic effects it  has and the use has mostly been without prescription, since it is a non- prescription drug. Therefore, the potential of dexamethasone to induce DM  was studied. Some of the drugs currently used in the treatment of diabetes have their own problematic effects and also expensive, Annona muricata methanolic bark extract (AMMBE) was used in the treatment of dexamethasone-induced diabetes in rats. The research was carried out on albino rats in Federal College of Animal Health and Production Technology, Ibadan and lasted for twenty-eight (28) days. The rats were allotted into four groups (A, B, C and D). Group B, C and D were induced with glucocorticoid (Dexamethasone) (2mgkg-1) daily for seven (7) days intraperitoneally,  while group A which was the positive control were given distilled water throughout without induction with glucocorticoid. Group B (the negative control) was induced with glucocorticoid with no AMMBE administration. Group C, was induced and treated with AMMBE at 400 mgkg-1for 14 days. While Group D, was induced with glucocorticoid and were treated with the standard drug (glibenclamide) at 2.5mgkg-1body weight of the rats daily  for 14 days. Organ samples of liver, kidney and pancreas were collected for histopathological lesions Evaluation. The result showed that  dexamethasone induced diabetes after seven (7) days of intraperitoneal administration of 2 mgkg-1 body weights with the glucometer readings in most of the albino rats up to and above 129 mgdL-1. The average blood sugar levels in induced groups (B, C and D) were 132.0±4.05, 129.0±1.41  and130.0±2.93, respectively which were not statistically significant (P>0.05). After administration of AMMBE, the average blood sugar level for group B (126.0±1.41) was significantly different (P<0.05) from C (91.0±1.72) and D (87.0±2.97). Clinical signs of alopecia, dehydration, writhing, paw-licking were observed. There were massive losses of pancreatic cell mass grossly after induction with dexamethasone. Histopathological lesions observed  ranges from no visible lesion in the control and glibenclamide treated groups to accentuation of hepatocytes in the AMMBE treated rats, and marked vacuolar degeneration of hepatocytes in periportal areas to centrilobular area with Kidney degeneration and multifocal coagulation  necrosis of tubular epithelium in group induced with dexamethasone but untreated (group B) degeneration, multifoci coagulation and necrosis. The blood sugar levels post exposure to AMMBE and Glibenclamide showed reduction in the sugar levels. It could be concluded that dexamethasone has the potential of inducing diabetes when its use is prolonged and AMMBE has antidiabetic effect which could be fully explored.

Keywords: Dexamethasone, Diabetes mellitus, Annona muricata, Albino rats, Histopathology