biostudies-literatureKabalı SOndokuz Mayıs University Scientific Research Fund56https://www.ebi.ac.uk/biostudies/studies/S-EPMC12840301biostudies-literatureUnknown48(1)<i>Aflatoxin</i><i>B1</i> (AFB1) is a hepatotoxic mycotoxin whose bioactivation by cytochrome P450 (CYP450) enzymes generates reactive metabolites that drive oxidative stress, inflammation, and apoptosis. Propolis is a bee-derived product with antioxidant and immunomodulatory properties. To investigate whether propolis supplementation attenuates AFB1-induced hepatic injury by modulating inflammatory mediators, Nrf2-HO-1 signaling, mitochondrial apoptosis, and CYP450 expression in rats, twenty-four male Sprague-Dawley rats were randomly allocated to four groups (n = 6): control, AFB1 (25 µg/kg/day), propolis (250 mg/kg/day), and AFB1 + propolis. Treatments were given by oral gavage for 28 days. Hepatic IL-1β, IL-6, TNF-α, Nrf2 and HO-1 levels were measured by ELISA. Histopathology was assessed on H&E-stained sections. Bax, Bcl-2, caspase-3, CYP1A2, CYP3A4, CYP2C19 and cytochrome P450 reductase expressions were evaluated immunohistochemically and quantified by ImageJ. Data were analyzed using one-way ANOVA with Tukey's post hoc test. AFB1 significantly increased hepatic IL-1β and IL-6 and reduced Nrf2 levels, while propolis supplementation restored Nrf2, elevated HO-1 and significantly lowered IL-6 compared with AFB1 alone (<i>p</i> < 0.05). AFB1 induced marked hydropic degeneration, sinusoidal congestion, and mononuclear infiltration, alongside increased Bax and caspase-3 and decreased Bcl-2 expression; these changes were largely reversed in propolis-treated groups. AFB1 upregulated CYP1A2, CYP3A4 and cytochrome P450 reductase, whereas propolis co-treatment significantly suppressed their expression without affecting CYP2C19. Propolis supplementation attenuated AFB1-induced liver injury through coordinated anti-inflammatory, antioxidant, anti-apoptotic and metabolic regulatory effects, notably via restoration of Nrf2-HO-1 signaling and down-regulation of key CYP450 isoenzymes. Propolis may represent a promising natural dietary strategy against AFB1-associated hepatotoxicity, warranting further translational research.Current issues in molecular biologyAlleviation of Aflatoxin B1-Induced Hepatic Damage by Propolis: Effects on Inflammation, Apoptosis, and Cytochrome P450 Enzyme Expression.PMC12840301OMU-BAP, Project No: PYO.SBF.1908.23.017Sogut MUKabalı SKara AOner NElgun ZfalseAlleviation of Aflatoxin B1-Induced Hepatic Damage by Propolis: Effects on Inflammation, Apoptosis, and Cytochrome P450 Enzyme Expression.<i>Aflatoxin</i><i>B1</i> (AFB1) is a hepatotoxic mycotoxin whose bioactivation by cytochrome P450 (CYP450) enzymes generates reactive metabolites that drive oxidative stress, inflammation, and apoptosis. Propolis is a bee-derived product with antioxidant and immunomodulatory properties. To investigate whether propolis supplementation attenuates AFB1-induced hepatic injury by modulating inflammatory mediators, Nrf2-HO-1 signaling, mitochondrial apoptosis, and CYP450 expression in rats, twenty-four male Sprague-Dawley rats were randomly allocated to four groups (n = 6): control, AFB1 (25 µg/kg/day), propolis (250 mg/kg/day), and AFB1 + propolis. Treatments were given by oral gavage for 28 days. Hepatic IL-1β, IL-6, TNF-α, Nrf2 and HO-1 levels were measured by ELISA. Histopathology was assessed on H&E-stained sections. Bax, Bcl-2, caspase-3, CYP1A2, CYP3A4, CYP2C19 and cytochrome P450 reductase expressions were evaluated immunohistochemically and quantified by ImageJ. Data were analyzed using one-way ANOVA with Tukey's post hoc test. AFB1 significantly increased hepatic IL-1β and IL-6 and reduced Nrf2 levels, while propolis supplementation restored Nrf2, elevated HO-1 and significantly lowered IL-6 compared with AFB1 alone (<i>p</i> < 0.05). AFB1 induced marked hydropic degeneration, sinusoidal congestion, and mononuclear infiltration, alongside increased Bax and caspase-3 and decreased Bcl-2 expression; these changes were largely reversed in propolis-treated groups. AFB1 upregulated CYP1A2, CYP3A4 and cytochrome P450 reductase, whereas propolis co-treatment significantly suppressed their expression without affecting CYP2C19. Propolis supplementation attenuated AFB1-induced liver injury through coordinated anti-inflammatory, antioxidant, anti-apoptotic and metabolic regulatory effects, notably via restoration of Nrf2-HO-1 signaling and down-regulation of key CYP450 isoenzymes. Propolis may represent a promising natural dietary strategy against AFB1-associated hepatotoxicity, warranting further translational research.2026-01-01T00:00:00Z2026 Jan2026-06-15T03:20:08.128Z2026-06-15T03:11:36.692ZS-EPMC128403014161488610.3390/cimb48010056