Comparative Biochemical and Histological Studies on the Toxic Effects of Thioridazine versus Pimozide on Some Organs of Adult Male Albino Rats

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 subacute toxic effects of the typical antipsychotic drugs Thioridazine (Melleril) and Pimozide (Orap) on some organs of adult male albino rats. Animals were divided into two main study groups. Group IAcute Toxicity Group included 18 rats which were divided equally into 3 subgroups; 6 rats each: Subgroup la: Ser ved as control. Subgroup lb received a single oral toxic dose of thioridazine (26.4 mg/100 gm B.W) and Subgroup Ic received a single oral toxic dose of pimozide (11 mg/100 gm B.W). Group 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 Ila: Served as control. Subgroup lib received dose equal to 1/20 of LD50 of thioridazine (5.4 mg/100gm B. W), Subgroup lie received dose equal to 1/10 of LD50 of thioridazine (10.8 mg/100 gm B. W). Subgroup lid received dose equal to 1/50 of LD50 of pimozide (2.2 mg/100 gm B.W). Subgroup He received 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, heart and testis 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, mean area % of collagen in ventricular sections and mean % of populated seminiferous tubules were measured using image analysis. Results were compared statistically. Results of the acute study revealed significant elevation in liver enzymes and LDH of ats receiving both drugs. Histological examination revealed no morphological alterations in rats which received thioridazine but there was congestion of blood vessels in liver, heart and kidney of rats received pimozide. 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 lId IIe). Moreover, urea and creatinine levels increased significantly with the intake of the higher toxic dose of each drug (subgroups lIe IIe). Concerning the histological assessment, lower toxic dose of thioridazine spared the liver, heart and testis, while the kidney sections showed distortion of glomerular capillary tufts, accompanied by widening of Bowman s space. Using the higher toxic dose of thioridazine as well as both doses of pimozide induced marked morphological alterations in all organs. Liver sections showed dilatation of central veins, blood sinusoids and portal veins. Kidney sections showed rarefaction of proximal tubules pyknosis of their nuclei. Ventricular sections showed cytoplasmic lysis of cardiomyocytes and interstitial hemorrhage. Testicular sections revealed disappearance of most of spermatogenic cells and vacuolations of Sertoli cells. From the previous results it could be concluded that the anti-psychotic drug pimozide proved to have more injurious and toxic effects than thioridazine.