Impact of environmental contaminants in fish on cell death and oxidative stress using in vivo, in vitro, and molecular docking

Abstract

Background: Fish species from the Red Sea constitute excellent food sources but may be unsafe to consume because their bioaccumulation of iron (Fe) is greater than the recommended concentration.

Objective: We investigated the safety concerns related to the consumption of fish containing iron.

Design: In this study, Wistar rats were treated with Fe(II) and Fe(III) at a total dose of ~200 mg/kg body weight. For cytotoxicity testing, human liver WRL-68, human hepatoma HepG2, and rat liver FTO2B cells were exposed to Fe(II) and Fe(III). Computational tools were utilized to assess the molecular interactions of iron with critical oxidative stress markers and predict potential toxicological outcomes.

Results: The in vivo results showed that only treatment with Fe2+ significantly (P < 0.05) changed aminotransferase activity compared to the control and caused an alteration in the oxidative balance, which was reflected by increases in the content of malondialdehyde (MDA) and the activities of antioxidant enzymes. The in vitro results revealed that the concentrations of Fe(II) and Fe(III) typically found in Red Sea fish were not toxic to these cell lines. However, the addition of Fe(III) potentiated the harmful effects of H2O2 in FTO2B cells. Moreover, the results demonstrate that exposure to Fe(III) resulted in increased (P < 0.05) expression of the superoxide dismutase (SOD) gene. The docking analysis revealed that Fe²⁺-Protoporphyrin exhibited strong binding to both SOD (–8.7 kcal/mol) and Catalase (–9.1 kcal/mol), as compared to its known inhibitors, suggesting a potential role in enzymatic inhibition and oxidative stress modulation.

Conclusion: The results reveal that there is a potential risk of toxicity when fish products are consumed. Further investigations are needed, especially in regard to determining the estimated weekly intake of these metals.