Protocatechuic acid protects against menadione-induced liver damage by up-regulating nuclear erythroid-related factor 2

Menadione (Vitamin K-3) is an over-the-counter (OTC) drug used in the treatment of abdominal cramps, colitis, diarrhea, hay fever, hemorrahage, hypoprothrombinemia, and joint pains. In this study, we evaluated the protective influence of protocatechuic acid on menadione-induced hepatotoxicity in rats. Rats were randomized into five groups (A-E) of five rats each. Control rats orally received 1% dimethyl sulfoxide (DMSO) in distilled water (the vehicle for protocatechuic administration) for 7 days. In addition, control rats intraperioneally received olive oil (vehicle for menadione administration) on the 7th day. Groups B, D, and E received single dose of 100 mg/kg body weight menadione on day 7. Furthermore, groups C-E were pretreated with protocatechuic acid for 7 days. Pretreatment of rats with protocatechuic acid significantly halted menadione mediated-alterations in serum alkaline phosphatase, alanine and aspartate aminotransferases, albumin, and total bilirubin. Furthermore, menadione-mediated increase in superoxide ion and hydrogen peroxide with concomitant decrease in the activities of superoxide dismutase and catalase were significantly reversed by protocatechuic acid. Protocatechuic acid annulled menadione-mediated decrease in glutathione S-transferase and NADH: quinone oxidoreductase-1 through nuclear erythroid related factor-2 (Nrf-2). In addition, the decreased glutathione and increased glutathione disulfide, caspase-3, fragmented DNA, malondialdehyde and protein carbonyl were reversed. Results of this study show that protocatechuic acid protects against menadione-induced oxidative stress in rats by enhancing the antioxidant and phase II enzymes through Nrf-2.