L’EXPÉRIMENTATION ANIMALE EN TOXICOLOGIE

Abstract

Introduction : Animal experimentation is essential in toxicology to evaluate the deleterious effects of chemical and pharmaceutical substances. This thesis focuses specifically on the hepatotoxicity of paracetamol, a widely used analgesic, using mice as an experimental model. The main objective of this research is to highlight the importance of animal experimentation in dissecting the mechanisms of paracetamol-induced liver toxicity and to measure the extent of liver damage based on different dosages. Additionally, determining the lethal dose 50 (LD50) was a key objective of this study. By adhering to OECD 423 guidelines, we established that the LD50 of paracetamol in laboratory mice is set at 300 mg/kg. This measurement is crucial for assessing the acute toxicity of paracetamol and providing crucial data for safety assessments and pharmacological regulations. Materials and Methods : The study was conducted by administering various doses of paracetamol to groups of mice, in accordance with OECD 423 guidelines, followed by observing the effects on liver function and liver structure. Mice were divided into several groups, including a control group and several experimental groups receiving increasing doses of 300 mg/kg and 2000 mg/kg of paracetamol. Biochemical parameters such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured to assess liver function. Additionally, histopathological analyses of liver tissue were performed to detect cellular and tissue lesions. Following OECD 423 guidelines, we were able to determine the lethal dose 50 (LD50), which was set at 300 mg/kg. Results : The results demonstrate a dose-dependent relationship between paracetamol administration and elevated transaminase levels, indicating dose-dependent liver damage. Histopathological analyses reveal significant lesions, including hepatic necrosis and inflammation, particularly pronounced at high doses, thereby proving the hepatotoxicity of paracetamol. Conclusion : In conclusion, this research illustrates the crucial importance of animal experimentation in assessing toxicological risks, especially for commonly used medications such as paracetamol. It deepens our understanding of paracetamol-induced hepatotoxic effects and convincingly demonstrates the value of animal models in toxicological risk assessments.