Hepatoprotective Effects of N-Acetylcysteine and Guarana in a Wistar Rat Model of Acute Acetaminophen Toxicity.

Acetaminophen overdose causes acute liver injury through oxidative stress, inflammation, and hepatocellular damage. This study evaluated the post-exposure effects of N-acetylcysteine (NAC), guarana, and their combination in a rat model of acute acetaminophen toxicity. Thirty male Wistar rats were randomly allocated to the Control, APAP, APAP + NAC, APAP + Guarana, and APAP + NAC + Guarana groups. Acetaminophen (3 g/kg) was administered orally on day 8. Treatments were initiated 4 h later and repeated on days 9 and 10; NAC was administered intraperitoneally at 1.5 g/kg, whereas guarana was administered orally at 300 mg/kg. Serum liver enzymes, circulating oxidative stress and antioxidant parameters, hepatic TNF-α and IL-1β levels, and liver histopathology were assessed. Acetaminophen increased serum AST, ALT, ALP, and catalase activities, serum MDA levels, and hepatic TNF-α and IL-1β levels, decreased serum SOD activity, and caused marked histopathological injury. Histopathological scores differed significantly among groups for all six evaluated parameters and the total liver injury score (all P < 0.001). NAC monotherapy improved selected biochemical and inflammatory outcomes and significantly reduced sinusoidal congestion, inflammatory cell infiltration, and architectural disruption relative to APAP. Guarana monotherapy showed numerical changes in several measures but did not differ significantly from APAP in the histopathological comparisons after multiplicity correction. Combined NAC and guarana treatment produced the broadest treatment-associated response and significantly lower histopathological scores than APAP across all evaluated parameters. These findings support further evaluation of guarana as a potential adjunct to NAC after acetaminophen exposure without establishing superiority over NAC or a synergistic interaction.