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Cytotoxic stimuli can include organic toxins such as hemorrhagic snake venom, which can lead to secondary complications such as the development of necrotic tissue and profuse scarring. These clinical manifestations mimic cytotoxic responses induce by other organic compounds such as organic acids. We used hemorrhagic snake venom and human embryonic kidney cells (HEK 293T) as a model system to better understand the cellular responses involved in venom induced cytotoxicity. Cells stimulated with <jats:styled-content style=\"fixed-case\"><jats:italic>Crotalus atrox<\/jats:italic><\/jats:styled-content> (CA) (western diamondback) venom for 4 or 10\u00a0h demonstrated significant cytotoxicity. Results from 2\u2032,7\u2032\u2010Dichlorodihydrofluorescein diacetate (H<jats:sub>2<\/jats:sub>DCF\u2010DA) assays determine CA venom stimulation induces a robust production of reactive oxygen species (ROS) over a 3\u2010h time course. In contrast, pretreatment with polyethylene glycol (PEG)\u2010catalase or N\u2010acetyl cysteine (NAC) prior to CA venom stimulation significantly blunted H<jats:sub>2<\/jats:sub>DCFDA fluorescence fold changes and showed greater cytoprotective effects than cells stimulated with CA venom alone. Pre\u2010 incubating HEK293T cells with the NADPH oxidase (NOX) pan\u2010inhibitor VAS2870 prior venom stimulation significantly minimized the venom\u2010induced oxidative burst at early timepoints (\u22642\u00a0h). Collectively, our experiments show that pre\u2010application of antioxidants reduces CA venom induce cellular toxicity. This result highlights the importance of ROS in the early stages of cytotoxicity and suggests muting ROS production in noxious injuries may increase positive clinical outcomes.<\/jats:p>","DOI":"10.1002\/jat.4262","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T02:59:59Z","timestamp":1635821999000},"page":"852-863","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp><i>Crotalus atrox<\/i><\/scp> venom\u2010induced cellular toxicity: Early wound progression involves reactive oxygen species"],"prefix":"10.1002","volume":"42","author":[{"given":"Lindsay E.","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biology Kennesaw State University  Kennesaw Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Reyes","sequence":"additional","affiliation":[{"name":"Department of Molecular and 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