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The current study has been designed to assess the role of Persea americana (P. americana) pulp extract on potassium dichromate‐induced hepatotoxicity in rats. P. americana pulp extract administration improved the hepatic vascular congestion, blood extravasation, inflammatory cellular infiltration, Kupffer cell hyperplasia, and nuclear changes. It also significantly ameliorated hepatic interstitial and peri‐portal fibrosis and caused retrieval of the PAS‐positive reaction in the liver parenchyma and around the central vein with restoration of the glycogen granules. P. americana also significantly attenuated the immunohistochemical expression of NF‐kβ p65 and its downstream inflammatory cytokines IL6 and TNFα in the liver parenchyma. The antioxidant effect of P. americana was evidenced by significant modulation of the three major components of the thioredoxin (Trx) antioxidant system, the Trx, the thioredoxin reductase (TrxR), and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase along with significant increase in the level of superoxide dismutase and glutathione, and decrease in the lipid peroxidation product malondialdehyde. P. americana pulp extract also caused significant elevation of hepatic protein phosphatase 5 with subsequent down‐regulation of Apoptosis signal‐regulating kinase1 (ASK1) and its downstream signaling targets MAPK kinase 4 (MKK4), p38 mitogen‐activated protein kinases (p38‐MAPKs), the c‐JUN N‐terminal kinase (JNK), and the extracellular signal‐regulated kinase 1/2 (ERK 1/2). Also, In conclusion, P. americana pulp extract has anti‐oxidative and anti‐inflammatory effects against potassium dichromate‐induced hepatotoxicity.

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