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Cobinamide, a Vitamin B12 Analog, Attenuates Benzo[a]pyrene and Pyrene Toxicity Through Selective Redox Modulation.
Anirudh Kalyanaraman1, Connor B Stauffer1, Weirui Gao1
1Department of Medicine, University of California, La Jolla, San Diego, CA 92093, USA.
Toxics
|May 27, 2026
Summary
Cobinamide effectively mitigates injury from polycyclic aromatic hydrocarbons (PAHs) like benzo[a]pyrene and pyrene by reducing oxidative stress. This vitamin B12 analog shows therapeutic potential against PAH toxicity in cellular and animal models.
Area of Science:
- Environmental Toxicology
- Biochemistry
- Pharmacology
Background:
- Polycyclic aromatic hydrocarbons (PAHs) are persistent environmental contaminants linked to mutagenic and cytotoxic effects.
- Benzo[a]pyrene (B[a]P) and pyrene are key PAHs, with B[a]P being a carcinogenicity benchmark and pyrene's metabolite a biomarker for exposure.
- PAH exposure generates reactive oxygen species (ROS) via metabolic activation, contributing to cellular damage.
Purpose of the Study:
- To investigate the efficacy of cobinamide, a vitamin B12 analog, in mitigating cellular and organismal injury induced by benzo[a]pyrene and pyrene.
- To elucidate the mechanisms by which cobinamide counteracts PAH-induced toxicity, focusing on oxidative stress and inflammatory pathways.
Main Methods:
- Exposure of H9C2 cardiomyoblasts and A549 lung epithelial cells to B[a]P and pyrene, with co-administration of cobinamide.
- Assessment of cell viability, metabolic activity, apoptosis, JNK/p38 phosphorylation, DNA/protein oxidation, and gene expression.
- Evaluation of cobinamide's effects on survival and locomotion in *Drosophila melanogaster* exposed to PAHs.
Main Results:
- Cobinamide attenuated PAH-induced reductions in cell number, metabolic activity, and apoptosis in cellular models.
- Cobinamide normalized stress signaling pathways, reduced DNA and protein oxidation, and modulated inflammatory and oxidative stress gene expression.
- In *Drosophila*, cobinamide significantly improved survival and restored locomotion, outperforming cobalamin and N-acetylcysteine.
Conclusions:
- Cobinamide effectively mitigates ROS-mediated PAH toxicity by modulating redox balance and inflammatory responses.
- The protective effects of cobinamide occur without direct binding to PAHs, suggesting a mechanism of action via cellular redox modulation.
- Cobinamide demonstrates significant therapeutic potential for mitigating PAH-induced toxicity, preserving essential xenobiotic metabolism.
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