Acute gonadal toxicity induced by Bothrops atrox venom in mice

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  Acute gonadal toxicity induced by Bothrops atrox venom in mice Abstract Bothrops atrox is responsible for most snakebite incidents in the Amazon region. Its venom is recognized for causing significant tissue damage and systemic effects. However, its effect on reproductive organs remains poorly explored. This study aimed to investigate the acute effects of B. atrox venom on testes and ovaries of adult mice. Male and female mice were exposed to B. atrox venom (½ LD 50 ) via four administration routes subcutaneous (SC), intramuscular (IM), intravenous (IV), and intraperitoneal (IP), followed by comprehensive assessment of gonadal histology, sperm function, oxidative stress biomarkers, antioxidant enzyme activities, and mRNA expression of inflammatory and apoptotic markers. Following B. atrox venom exposure, ovarian histological architecture remained preserved across all routes, whereas testicular tissue exhibited route-dependent injury ranging from moderate luminal apoptosis aft...

A Paradigm Shift in Snakebite Envenoming Therapy: From Conventional Antivenoms to Rationally Designed, Broadly Neutralizing Combination Therapies

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A Paradigm Shift in Snakebite Envenoming Therapy: From Conventional Antivenoms to Rationally Designed, Broadly Neutralizing Combination Therapies

Abstract

For over a century, polyclonal antivenom has been the cornerstone of snakebite therapy, saving countless lives. However, the current production method, based on immunizing large animals, has inherent limitations in terms of safety, stability, and supply reliability, thereby creating a pressing need for alternative technologies. This review charts the rise of next-generation antivenoms built on recombinant antibody engineering. We systematically survey the strategies for discovering and developing these molecules, from humanized monoclonal antibodies and VHHs to computationally designed proteins. Our central thesis is that achieving broad-spectrum neutralization against complex venoms requires a shift from single-agent approaches to rationally designed, oligoclonal “cocktail” therapies (defined mixtures of a few select therapeutic antibodies). Finally, we analyze the critical challenges in bioprocessing, formulation, and regulatory science that must be overcome to translate these promising candidates from the laboratory into globally accessible medicines, and we explore the role of emerging technologies in accelerating this transition.

A Paradigm Shift in Snakebite Envenoming Therapy: From Conventional Antivenoms to Rationally Designed, Broadly Neutralizing Combination Therapies
Ning Shi, Jie Wang, Can Xu, Xingjun Jiang, Caiping Ren, Xiang Gao, and Longlong Luo
ACS Pharmacology & Translational Science Article ASAP
DOI: 10.1021/acsptsci.6c00130