Protective Effect of Lycopene on Patulin-Induced Liver Injury in Mice

Patulin (PAT) is a mycotoxin that contaminates apples and apple products and is a recognised hepatotoxicant, but practical dietary countermeasures remain undefined. We asked whether lycopene (LYC), a carotenoid antioxidant, limits PAT-induced liver injury in mice. Male Kunming (KM) mice (n = 8 per group) received PAT at 15 μmol kg^-1 body weight (BW) per day (2.31 mg kg^-1 BW per day), LYC at 5, 20 or 40 mg kg^-1 BW per day, or both, by oral gavage for 28 days. PAT lowered food intake and terminal body weight, raised serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) by 96.9 % and 52.0 %, increased hepatic malondialdehyde (MDA) by 76.4 %, and depressed total superoxide dismutase (SOD) activity. Blinded semi-quantitative scoring confirmed hepatocellular injury (0.63 in controls versus 7.75 in PAT-treated mice, out of 12). PAT also raised Grp78, Chop, Bax and lowered Bcl-2. Co-administered LYC attenuated every one of these changes. Protection saturated rather than scaling with dose: a composite hepatic injury index was attenuated by 50.3 %, 84.9 % and 78.3 % at 5, 20 and 40 mg kg^-1 BW. The gain between 5 and 20 mg kg^-1 BW was significant (P < 0.001), whereas no further benefit was obtained at 40 mg kg^-1 BW, the two highest doses being statistically indistinguishable (P = 0.24).Thus,the protective effect of LYC did not increase indefinitely with dose. These findings support bracketing the effective intake of LYC as a dietary countermeasure against PAT exposure.