Acetaminophen (AMP)-induced hepatotoxicity (AIH) is the critical side effect associated with high-dose exposure. N-acetylcysteine (NAC) is the gold standard to preserve the liver against AMP toxicity, with some drawbacks, leading to the search for alternative therapy. The antioxidant properties of methylene blue (MB), make its application plausible for AIH, as an additive therapy with NAC or alone. Therefore, the present study aimed to define the histological impact of MB on hepatoprotection. A total of 49 rats were enrolled in the present study. Rats were sub-classified into 7 groups: control group, AMP group, MB group, prophylaxis-MB low dose, prophylaxis-MB high dose, treatment-MB low dose, and treatment-MB high dose. Liver histopathological changes were examined under a microscope, and images were taken for all groups. Photomicrograph of a rat's liver section in the control group exposed to normal saline showing intact tissue. Rat liver sections from the AMP-treated group demonstrated central venous dilatation and severe portal inflammation. Rat liver section in the MB-50 prophylaxis group demonstrated mild portal inflammation with an increase in ductular proliferation. Rat liver section in the MB group with portal tracts, with no significant pathology. A rat liver section from the MB-100 prophylaxis group demonstrated a mild increase in portal ductules. The rat liver section in the MB-50 and MB-100 treatment group demonstrated a liver with a normal central vein. The MB intervention demonstrated marked protective effects against AIH in experimental rats, with interventional treatment providing better resolution than prophylaxis; nevertheless, both interventions were effective in blocking hepatotoxicity.
