Abstract

To investigate the protective effects of Nigella sativa seed extract (NSSE) against acetaminophen (APAP)-induced hepatotoxicity in TIB-73 cells and rats. Toxicity in TIB-73 cells was induced with 10μmol/L APAP and the protective effects of NSSE were evaluated at 25, 50, 75, 100μg/mL. For invivo examination, a total of 30 rats were equally divided into five experimental groups; normal control (vehicle), APAP (800mg/kg body weight single IP injection) as a hepatotoxic control, and three APAP and NS pretreated (2 weeks) groups (APAP+NSSE 100mg; APAP+NSSE 300mg and APAP+NSSE 900mg/kg). TIB-73 cell viability was drastically decreased by (49.0±1.9)% after the 10μmol/LAPAP treatment, which also increased reactive oxygen species production. Co-treatment with NSSE at 25, 50, 75, and 100μg/mL significantly improved cell viability and suppressed reactive oxygen species generation. Invivo, the APAP induced alterations in blood lactate levels, pH, anionic gap, and ion levels (HCO3(-), Mg(2+) and K(+)), which tended to normalize with the NSSE pretreatment. The NSSE also significantly decreased elevated serum levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase induced by APAP, which correlated with decreased levels of hepatic lipid peroxidation (malondialdehyde), increased superoxide dismutase levels, and reduced glutathione concentrations. Improved hepatic histology was also found in the treatment groups other than APAP group. The invitro and invivo findings of this study demonstrated that the NSSE has protective effects against APAP-induced hepatotoxicity and metabolic disturbances by improving antioxidant activities and suppressing both lipid peroxidation and ROS generation.

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