Short-term oral administration of risperidone induces pancreatic damage and hyperamylasemia in Sprague-dawley rats

Abstract

Risperidone is an atypical antipsychotic acting mainly as a dopamine D 2 and serotonin 5-HT 2 receptors antagonist prescribed in the treatment of schizophrenia and various affective disorders. Risperidone has been reported to be associated with weight gain, panreatitis and type 2 diabetes mellitus. Various mechanisms of risperidone-induced toxicities have been reported but the histology of tissues especially pancreas has never been studied. Therefore, the current study was designed to elucidate the toxic effects of chronic administration of risperidone on pancreas, liver and kidneys. Animals (rats) of either gender were divided into two groups, the risperidone and control groups. Risperidone was administered in a dose of 2.5 mg/kg/d for three weeks. The controls received acidified saline only. Both the groups received restricted diet (20 g/12 h). The body weight and level of random blood sugar (RBS) were measured on a weekly basis. The levels of lipase and amylase were determined at the conclusion of the experiment. At the end of the experiment, the tissues were dissected out for histopathological evaluation. Risperidone showed no weight gain, hyperglycemia or rise in the level of lipase (P> 0.05); however, the level of amylase was raised (***P<0.05). Histological examination under light microscope showed no hepatotoxicity, nephrotoxicity but did show damage to the pancreas. The findings of this study indicated that the incidence of adverse effects associated with risperidone could be prevented/alleviated/delayed by allowing restricted diet.Keywords: Risperidone/antipsychotics/oral administration/effects. Histopathology. D 2 antagonist. Pancreas. FIGURE 13 -Effect of risperidone on the liver of rats (H & E, 100x, 3 µ): Representative images of liver of rats treated with risperidone (2.5 mg/kg/d orally for three weeks showing no hepatic architectural changes as compared to normal saline treated rats. Short-term oral administration of risperidone induces pancreatic damage and hyperamylasemia in Sprague-dawley rats Braz.

Histological and Biochemical Changes Associated with Blocking of Serotonin Receptor

“…21 Evidence suggests that aripiprazole causes the fewest extrapyramidal symptoms (EPS), cardiovascular adverse effects, serum prolactin increase, and weight gain. 22 Hepatic performance after treatment with atypical antipsychotics was evaluated in a trial that significantly reduced GOT, GPT, ALP, and bilirubin, with no difference between males and females and no values outside the normal range. However, the slight increase in liver enzyme levels observed in this study could indicate an adaptive organ response.…”

Effects of cannabidiol on vacuous chewing movements, plasma glucose and oxidative stress indices in rats administered high dose risperidone

“…In contrast, risperidone has been shown to induce oxidative stress in the liver through increased reactive oxygen species (ROS) production, thus leading to mitochondrial collapse, lysosomal membrane disruption, GSH depletion and lipid peroxidation 34 . Pancreatic damage, including pancreatitis, is also associated with risperidone [35][36][37] , and oxidative stress may play a role here as pancreatitis is associated with oxidative stress [38][39][40] . The damage to pancreatic β cells following AAP-induced glucose intolerance may be related to increased free radical production 41,42 .…”