What does this research mean for the field?

Cobinamide, a vitamin B12 analog, mitigates benzo[a]pyrene- and pyrene-induced toxicity in vitro and in vivo through selective redox modulation and reduction of reactive oxygen species. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The study aims to evaluate the efficacy of cobinamide in mitigating the toxic effects of benzo[a]pyrene and pyrene in cell models.

May 17, 2026Toxics0 citationsOpen Access

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Cobinamide, a Vitamin B12 Analog, Attenuates Benzoapyrene and Pyrene Toxicity Through Selective Redox Modulation

AKAnirudh KalyanaramanUniversity of California, San Diego CSConnor B. StaufferUniversity of California, San Diego WGWeirui GaoUniversity of California, San Diego

Key Points

The study aims to evaluate the efficacy of cobinamide in mitigating the toxic effects of benzo[a]pyrene and pyrene in cell models.
In vitro analysis in H9C2 and A549 cells exposed to B[a]P and pyrene with cobinamide treatment.
Assessment of cell number, metabolic activity, apoptosis, and gene expression changes.
In vivo evaluation in Drosophila melanogaster with survival and locomotion metrics after PAH exposure and cobinamide administration.
Cobinamide significantly decreased cell death and improved metabolic activity in H9C2 cells exposed to B[a]P and pyrene.
It reduced apoptosis and oxidative damage, returning JNK/p38 phosphorylation to baseline levels.
In Drosophila, cobinamide improved survival and locomotion, outperforming cobalamin and N-acetylcysteine.

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are common environmental contaminants formed during the incomplete combustion of organic material. Their persistence, bioaccumulation, and metabolic activation contribute to mutagenic and cytotoxic outcomes. Among these are benzoapyrene (BaP), the most studied PAH and a benchmark compound for PAH carcinogenicity, and pyrene, a PAH whose urinary metabolite 1-hydroxypyrene is widely used as a biomarker of PAH exposure. BaP undergoes CYP1A1-mediated oxidation to generate reactive oxygen species (ROS) via epoxide and quinone redox cycling, whereas pyrene produces ROS primarily through pyrene-quinone redox cycling. We investigated cobinamide, a vitamin B12/cobalamin analog with potent antioxidant properties, for mitigating benzoapyrene- and pyrene-induced injury. In H9C2 rat embryonic cardiomyoblasts and A549 human lung epithelial cells exposed to BaP (10 μM) or pyrene (10–100 μM), cobinamide (5–10 μM) attenuated PAH-induced reductions in cell number in both models, while in H9C2 cells, it also attenuated decreases in metabolic activity and reduced apoptosis. Cobinamide also returned JNK/p38 phosphorylation to near baseline levels, decreased DNA and protein oxidation and DNA strand breaks. Transcriptionally, cobinamide suppressed inflammatory (TNF-α, IL-1β, and IL-6) and oxidative stress genes (HMOX1 and NOX4), while enhancing oxidative response (SOD2) and xenobiotic metabolism (CYP1A1). In Drosophila melanogaster exposed to 5 mM BaP/pyrene, 2 mM cobinamide improved survival and fully restored locomotion, outperforming cobalamin (minimal benefit) and N-acetylcysteine (partial rescue). Spectroscopic analyses showed no direct cobinamide-PAH binding. These findings demonstrate that cobinamide efficiently limits ROS-mediated PAH injury through redox modulation while preserving xenobiotic metabolism, suggesting its potential therapeutic use to mitigate PAH-induced toxicity.

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Cite This Study

Kalyanaraman et al. (Fri,) studied this question.

synapsesocial.com/papers/6a095bef7880e6d24efe1e29 https://doi.org/https://doi.org/10.3390/toxics14050439

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