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Acetaminophen (APAP), widely used as an analgesic-antipyretic drug, can cause liver and kidney damage at high doses. This study explored the protective effects of a mucolytic agent and an antioxidant Ambroxol (AMB), against APAP-induced toxicity in rats. The experiment included four groups of Wistar albino rats each having 6 animals in both sexes: a control group, an AMB-only group (50 mg/kg orally), an APAP-only group (1000 mg/kg intraperitoneally), and a combination APAP+AMB group. Twenty-four hours following the administration of APAP administration, rats were sacrificed. Measurements of blood levels of liver enzymes (AST, ALT, ALP, LDH), kidney function markers (Urea, Creatinine), and antioxidant enzymes (SOD, GPx) were performed. GPx and SOD activities were also assessed in hepatic and renal tissue samples. Histological examination of hepatic and renal tissues was conducted using Haematoxylin and Eosin staining. Results showed that APAP significantly increased liver enzymes, BUN, and Creatinine levels, indicating hepatorenal damage. This was accompanied by a decrease in plasma GPx and SOD activities. However, AMB treatment significantly mitigated these changes. It improved enzyme activities and increased hepatic GPx. Histologically, the APAP group showed liver cell damage, necrosis, haemorrhage, and inflammation, which were notably reduced in the AMB-treated group. This study suggests that Ambroxol effectively counters APAP-induced hepatorenal damage by restoring antioxidant enzyme levels and normalizing functional enzyme activities, highlighting its potential as a protective agent. [ABSTRACT FROM AUTHOR]