Investigation of Hepatotoxicity after a neuroleptic overdose

Abstract

Among all of the organs in the human body, the liver performs the greatest number of functions. The liver’s multiple activities are important and have impacts on all body systems, including the nervous system. It is also in the liver that most of the substances that we ingest are metabolized, including drugs. Liver failure occurs when large parts of the liver become damaged beyond repair, and the liver is no longer able to function. Drug-induced liver injury (DILI) is the 4th most important cause of liver disease ,among these drugs, the neuroleptics which are beneficial for the management of behavioral disorders, but they still can cause adverse effects or aggravate some conditions such as hepatotoxicity especially if the patient did not respect the prescribed dose so that he falls in the danger of overdose . In this study we were interested in the investigation and evaluation of hepatotoxic effects after a sub-chronic (45 days) and an acute (72hours) overdosing of a neuroleptic drug “Chlorpromazine “ in the liver of rattus Wistar rats .our study was planned in 4 axes of experimentation ; study of general body changes ; determination of biochemical parameters (blood analysis) ;evaluation of metabolites; and evaluation of oxidative stress parameters at different levels (mitochondrial and cellular).our sub-chronic treatment results shows an increase of ( lipids; proteins ; TG; Mitochondrial MDA ; GSH ; Mitochondrial GSH ; GPx ;CAT ;Alkaline Phosphatase ; Totale Bilirubine . Direct Bilirubine and LDH ). And a decrease of (body weight ; MDA ; ASAT ; ALAT; Albumine )In the other hand the acute treatment results shows an increase of ( ALAT ; Albumine ; TG; Lipids ; Proteins; MDA ; Mitochondrial MDA ; GSH ; Mitochondrial GSH; GPx ; CAT ; Alkaline Phosphatase ; Direct Bilirubine ; Totale Bilirubine ; LDH ) and a decrease of (body weight ; ASAT and Mitochondrial GPx ) These results signifies that the overdose of “Chlorpromazine” leads to hepatotoxicity and can cause liver injury .CZP may interact with various cellular organelles such as mitochondria leading to hepatocyte dysfunction .