The capability of lophirones B and C to extenuate aflatoxin B-1 (AFB(1))-mediated onslaught on cellular proteins, lipids, and DNA was investigated for 6 weeks. Lophirones B and C significantly (P < 0.05) increase the expression and specific activity of cytoprotective enzymes (glutathione-S-transferase, nioctinamide adenine dicludeotide: quinone oxidoreductase-1, epoxide hydrolase, and uridyl glucuronosyl transferase). There was significant (P < 0.05) reduction in the level of antioxidant system in AFB(1)-induced hepatocarcinogenesis. Furthermore, lophirones B and C significantly (P < 0.05) attenuated AFB(1)-mediated decrease in the specific activities of antioxidant enzymes. Oxidative stress biomarkers, malondialdehyde, lipid hydroperoxides, conjugated dienes, protein carbonyl, and fragmented DNA were significantly (P < 0.05) elevated in AFB(1)-treated rats. Although lophirones B and C did not significantly (P < 0.05) alter these biomarkers, an AFB(1)-mediated increase in these biomarkers was significantly attenuated. Results obtained showed that lophirones B and C extenuate AFB(1)-mediated onslaught on cellular proteins, lipids, and DNA by enhancing nuclear erythroid-related factor-2 expression. (C) 2014 Wiley Periodicals, Inc.