Preventive effects of quercetin and N-acetylcysteine, alone and combined, against acetaminophen-induced hepatotoxicity in rats: associations with COX-2/TGF-β1 and Nrf2/HO-1 mRNA expression

Abstract

This study evaluated the preventive effects of quercetin (QR) and N-acetylcysteine (NAC), alone or combined, in a rat model of acute acetaminophen (APAP)-induced hepatotoxicity. Twenty-five male rats were allocated to five groups (n = 5): control, APAP, NAC + APAP, QR + APAP, and NAC + QR + APAP. NAC (150 mg/kg) and/or QR (50 mg/kg) were administered orally for 7 days before a single oral APAP dose (2 g/kg). Serum liver-function indices, lipid profile, circulating TNF-α and IL-6, hepatic oxidative-status indices, hepatic COX-2, TGF-β1, Nrf2, and HO-1 mRNA abundance, histopathology, and IL-1β immunohistochemistry were assessed. APAP increased ALT, AST, triglycerides, total cholesterol, TNF-α, IL-6, and hepatic MDA, while decreasing total protein, albumin, HDL-C, GSH, CAT, SOD, and GPx. It also increased COX-2 and TGF-β1 transcripts and decreased Nrf2 and HO-1 transcripts. Pretreatment with NAC or QR partially attenuated these changes, whereas their combination generally produced values closer to control. The combined regimen also reduced histological injury and IL-1β immunoreactivity relative to APAP. These findings support a preventive association between combined NAC/QR exposure and improved redox and inflammatory indices. Because protein abundance, Nrf2 nuclear translocation, treatment after injury, and treatment-only controls were not evaluated, the data do not establish pathway activation, pharmacological synergy, or therapeutic efficacy after established overdose.