Chronically Administered Risperidone Did Not Change the Number of Hepatocytes in Rats: A Stereological and Histopathological Study

Abstract

Risperidone, an antipsychotic agent, has been used in the therapy of patients with acute and chronic schizophrenia. The strategy in the choice of antipsychotic agent should take into account the hepatic tolerance. The aim of the present study was to analyse whether or not the chronic administration of risperidone has a toxic effect on rat livers. Rats were divided into three groups. Low dose (n = 5) and high dose (n = 5) groups that were given 0.5 and 1 mg/kg intraperitoneal doses of risperidone daily for 6 weeks, respectively. The control group received distilled water as a vehicle. At the end of the experiment, the rats were killed, and livers were dissected out immediately and transferred into the fixation solution. Both conventional light and transmission electron microscopic tissue preparation procedures were applied to liver tissues and they were evaluated using stereological and histopathological methods; in this respect, this is the first study using stereological methods for searching the effects of risperidone on liver. There were no significant differences about the total hepatocyte number and their numerical density of rat liver between groups (P > 0.05). Stereological results were also confirmed by the histopathological findings that come from both structural and ultrastructural levels examination. The results of the current study indicate that neither low nor high doses of risperidone resulted in damage to the rat livers at cellular level. In conclusion, we did not find any evidence for hepatotoxicity of risperidone rats. Larger-scale, prospective studies are needed in order to confirm these findings.Antipsychotic agents are divided by two main categories: typical or conventional and atypical. Risperidone is a potent antipsychotic agent that was introduced into clinical practice in 1993 and is commonly used in the management of both positive and negative symptoms of schizophrenia by reducing the extrapyramidal symptoms [1]. Due to the lower incidence and severity of adverse effects in comparison to phenothiazines, risperidone has been widely used in recent years [2]. Classed among the atypical antipsychotic drugs, major targets for risperidone action are dopaminergic D 2 receptors and serotonergic 5-HT 2 receptors [3]. Risperidone has shown a higher affinity for 5-HT 2 (five times) and α 1 (two times) receptors than D 2 receptors. Thus, risperidone has shown a broad spectrum of brain neurotransmitter receptors as previously reported [3,4]. Although antipsychotics are commonly used as a drugs in schizophrenia treatment, they are admittedly known to induce side effects such as impairment of fat cell lipolysis by altering the lipid metabolism [5], changing of whole-body insulin sensitivity in a dose-dependent [6], alterations in the striatal protein profile that may be involved in antipsychotic drug-induced extrapyramidal symptoms include metabolic dysfunction and oxidative stress [7]. Well-known adverse reactions to risperidone mainly involve the central nervous system and gastrointestinal ...

Omega-3 fatty acid deficiency augments risperidone-induced hepatic steatosis in rats: Positive association with stearoyl-CoA desaturase

“…It is also relevant that hepatic steatosis increases vulnerability to hepatotoxicity [4]. Although a prior histological study did not observe reductions in hepatocyte number following 42-day RSP treatment in rats maintained on n -3 fatty acid-fortified diet [74], additional histological studies are warranted to investigate whether low LC n -3 fatty acid status additionally increases vulnerability to RSP-induced hepatotoxicity.…”

Histopathological and Histomorphometric Studies on the Effects of Olanzapine on Vas Deferens and Urinary Bladder: An Experimental Study in Albino Rats.

“…Formation of reactive oxygen species is induced by the use of olanzapine which might cause cellular damage and dysfunction. [8,9] It has been proved that using antioxidant can reduce the metabolic changes in rats receiving olanzapine. [10] Reactive oxygen species could also be generalized reason for changes in organs under consideration.…”

Nephrotoxic Effects of Chronically Administered Olanzapine and Risperidone in Male Rats

“…Risperidone which was bought from Janssen Turkey, Istanbul, Turkey was also dissolved in normal saline (0.9% NaCl) and given intraperitoneally (12,20) in doses once a day for 6 weeks (0.5 and 1 mg/kg/day for the LRG and HRG, respectively). Risperidone at doses of 1 mg/kg were chosen as equivalent to the highest dosage used in human beings (12,22).…”