Role of Regulated Cell Death Pathways in Snakebite Envenomation: Mechanisms, Crosstalk, and Therapeutic Opportunities

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  Role of Regulated Cell Death Pathways in Snakebite Envenomation: Mechanisms, Crosstalk, and Therapeutic Opportunities Abstract Snakebite envenomation causes severe tissue damage, often resulting in permanent disability with long-term complications like amputations and organ dysfunction. Current antivenoms, which are antibody-based, have lower tissue penetrability and limited efficacy in minimizing the local effects, highlighting the need for adjunct therapies. Emerging evidence indicates that venom-induced pathology is not restricted to direct cytotoxicity and necrosis; rather, it also involves multiple interconnected Regulated Cell Death (RCD) pathways, but their mechanistic interplay and therapeutic implications remain poorly understood. This review examines how venom toxins induce a cellular stress response characterized by oxidative stress, membrane disruption, and calcium overload, leading to the activation of interconnected regulated cell death (RCD) pathways, including apo...

Proteomic profiling and biochemical characterization of enzymatic and non-enzymatic proteins of Heterometrus bengalensis venom and their pathophysiological functions in the Swiss albino mice model

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Proteomic profiling and biochemical characterization of enzymatic and non-enzymatic proteins of Heterometrus bengalensis venom and their pathophysiological functions in the Swiss albino mice model

Abstract

Due to its significant mortality and morbidity, scorpion sting is a public health concern worldwide, particularly in tropical and subtropical regions. Heterometrus bengalensis (HB) significantly impacts health; however, HB's venom composition is the least characterized. The present study provides a comprehensive insight into the HB venom (HBV) profile by in vitro enzyme assay and tandem mass spectrometry analysis of SDS-PAGE-separated venom proteins and peptides. HBV showed calcium-dependent PLA2 and nucleotidase (ATPase, ADPase, and AMPase) activities, indicating myotoxicity and ATP-depletion-induced shock. Proteomic analysis of HBV identified 25 toxins belonging to 8 protein toxin families from searching the MS data against the Scorpionidae family (taxid 6888) of toxin entries, which collectively contribute to the pharmacological effects of HBV. The lethal dose of HBV in Swiss albino mice (SAM) was determined to be 20 mg/kg (i.v). In vivo, HBV-envenomed SAM revealed severe physiological disturbances, elevated liver enzymes, plasma glucose levels, histopathological evidence of organ damage, and myotoxicity. The serum proinflammatory cytokines (IL-1β, IL-6, and TNFα) in HBV-injected SAM were significantly increased (1–2 fold) compared to the controls. The current findings underscore the complexity of HBV, highlighting the urgent need for improved therapeutic strategies, including the development of species-specific and targeted antivenom.
Nath, S., Mahato, R., Kakati, H., & Mukherjee, A. K. (2025). Proteomic profiling and biochemical characterization of enzymatic and non-enzymatic proteins of Heterometrus bengalensis venom and their pathophysiological functions in the Swiss albino mice model. International Journal of Biological Macromolecules, 146181. https://doi.org/10.1016/j.ijbiomac.2025.146181