Abstract
Background:
Paracetamol is one of the most popular drugs; it is used daily by many people especially the elderly, without a limitation on the length of the period allowed for continuous use. Harms from long-term use are less clear, particularly in extrahepatic regions.
Aim:
This study aimed to investigate whether using paracetamol at a NOAEL (non-observable adverse effect level) dose, known not to cause toxic effect, for long period can induce toxicity in aged male albino rats.
Methods:
A daily dose of 500 milligrams per kg body weight of paracetamol was given to adult male albino rats for 12 weeks. During this period, rats were sacrificed at 4, 6, 8, 10, and 12 weeks to evaluate the toxic changes at several time intervals.
Results:
Chemical analysis revealed elevated serum ALT, AST, ALP, urea, creatinine, and declined level of total protein in N-acetyl-p-aminophenol (APAP)-treated group; it also caused oxidative stress, as shown by decreased GSH, SOD, and elevated MDA in the liver, kidney, and brain. Histopathological examination demonstrated cytoplasmic vacuolation and sinusoidal congestion with the development of single-cell necrosis in the liver. Renal tubular necrosis and glomerular atrophy, and ischemic neuronal injury, especially in the hippocampus were observed. the deleterious effects of APAP were increased in severity with increasing the period of treatment.
Conclusion:
Our results suggest that acetaminophen in a subtoxic dose for a long period could result in mild toxic effects on the liver but more serious lesions in kidney, and brain.

Key words: Drug side effects, Paracetamol toxicity, Prolonged drug use, Analgesics