Acute and Subchronic Toxic Effects of Thioridazine versus Pimozide on Liver, Kidney and Heart of Adult Male Albino Rats: Biochemical and Histological Study

Abstract

Antipsychotic drugs are potent drugs that therapeutically modify behavior. They are widely used all over the world. This study was planned to compare the biochemical and histological alterations induced by acute and subchronic toxic effects of the typical antipsychotic drugs Thioridazine (Melleril) and Pimozide (Orap) on liver, kidney and heart of adult male albino rats. Animals were divided into two main groups. I Acute Toxicity Group included 18 rats that were divided equally into 3 subgroups; 6 rats each: subgroup Ia: served as control. Subgroup Ibreceived a single oral toxic dose of thioridazine (26.4 mg/100 gm B.W) and subgroup Icreceived a single oral toxic dose of pimozide (11 mg/100 gm B.W). II Subchronic Toxicity Group included 30 rats which were divided equally into 5 subgroups; 6 rats each that were given daily doses of the drugs orally for 12 weeks: Subgroup IIa: Served as control.Subgroup IIbreceived dose equal to 1/20 of LD50 of thioridazine (5.4 mg/100gm B.W), Subgroup IIc received dose equal to 1/10 of LD50 of thioridazine (10.8 mg/100 gm B.W).Subgroup IIdreceived dose equal to 1/50 of LD50 of pimozide (2.2 mg/100 gm B.W). Subgroup IIereceived dose equal to 1/25 of LD50 of pimozide (4.4 mg/100 gm B.W). At the end of the experiment, blood samples were taken for biochemical analysis of liver transaminases (serum AST, ALT levels), serum LDH, cholesterol level and kidney function tests (urea, creatinine, and uric acid levels). Sections from the liver, kidney and heart were subjected to H&E stain (those from liver and heart were also stained with Masson′s Trichrome). Mean sinusoidal area in liver sections, mean glomerular area in kidney sections and mean area % of collagen in ventricular sections. Results were compared statistically. Results of the acute study revealed significant elevation in liver enzymes and LDH of rats receiving both drugs as well as some morphological alterations in pimozide group. Biochemical changes in subchronic study showed significant elevation of liver enzymes and LDH in rats receiving both drugs at both doses. Cholesterol level increased significantly only with intake of pimozide (subgroups IId and IIe). Moreover, urea and creatinine levels increased significantly with the intake of the higher toxic dose of each drug (subgroups IIc and IIe). Concerning the histological assessment, lower toxic dose of thioridazine spared the liver and heart while affecting the kidney sections. Using the higher toxic dose of thioridazine as well as both doses of pimozide induced marked morphological alterations in all organs. In conclusion, both drugs tested in the current work proved to have definite toxic effects on the liver, kidney and heart. However, pimozide was more injurious and toxic than thioridazine. Thus, they should be prescribed under restricted conditions and periodic assessment of cardiac, hepatic and renal functions should be done detect early toxic effects.