The Mechanism of Development of Isoniazid and Rifampicin Induced Hepatotoxicity in Different Age Groups of Rats

Abstract

SECTION 7. THEORETICAL MEDICINE The mechanism of development of isoniazid and rifampicin induced hepatotoxicity in different age groups of ratsMultiple drugs, both prescription and over-the-counter, herbal products, or toxins can cause hepatotoxicity through a variety of mechanisms [407, 408]. According to World Health Organization statistics, drug-induced liver injury has risen as the 5th leading cause of death worldwide. Approximately 50% of liver failure patients receiving liver transplantation every year have drug-induced liver failure, which prompts the need for artificial liver and liver transplantation and even causes death [409]. However, the disease is often undiagnosed or misdiagnosed clinically because of diagnostic difficulties caused by lack of laboratory specific serological markers.The probability of an individual drug causing liver injury ranges from 1 in 10,000 to 100,000, with some drugs reported as having an incidence of 100 in 100,000 (chlorpromazine, isoniazid) [410]. Drugs can cause liver cell necrosis as foreign antigens by activating the immune system and then mediating corresponding injuries.According to recent studies, microRNA (miR)-122, as a highly liver-specific miR, can be used as a molecular marker of hepatocellular injury [411], whose specificity and sensitivity are significantly higher than alanine aminotransferase in the early diagnosis of APAP-induced drug-induced liver injury [412]. Some pathological findings may be relatively specific. The common histopathological changes in the liver may include ballooning changes or microvesicular steatosis, eosinophil infiltration, epithelial cell granuloma and cholestasis, but pathological evidence makes sense only in combination with medical history and other clinical data.There are various factors that enhance a person's susceptibility to a potentially hepatotoxic drug. Advancing age, gender, lifestyle factors, obesity, nutritional status, genetic background, dose, and duration of drugs may affect the risk of drug-mediated hepatotoxic reactions. Persons suffering from other diseases, such as, human