Sharma Rachana D, Katkar Gajanan D, Sundaram Mahalingam S, Swethakumar Basavarajaiah, Girish Kesturu S, Kemparaju Kempaiah
Department of Studies in Biochemistry, University of Mysore, Mysore, India.
Department of Studies and Research in Biochemistry, Tumkur University, Tumkur, India.
Acta Trop. 2017 May;169:14-25. doi: 10.1016/j.actatropica.2017.01.004. Epub 2017 Jan 12.
Snakebite is a neglected health hazard. Its patho-physiology has largely been focused on systemic and local toxicities; whereas, venom and antivenom induced oxidative stress has long been ignored. Antivenom therapy although neutralizes venom lethality and saves many lives, remains ineffective against oxidative stress. This prompted us to complement antivenom with an antioxidant molecule melatonin that would protect against oxidative stress and increase the efficacy of the existing snakebite therapy. Here we show that D. russelli and E. carinatus venoms induce strong oxidative stress that persists even after antivenom administration in mice model. Additionally, antivenoms also induce oxidative stress. Polyvalent antivenom induce more oxidative stress than monovalent antivenom. Strikingly, antivenom and melatonin together not only inhibit venom and antivenom induced oxidative stress but also significantly reduce the neutralizing antivenom dose. This study provides a therapeutic potential for enhancing the existing snakebite therapy. The combined treatment of antivenom+melatonin would prevent the upsurge of oxidative stress as well as minimize the antivenom load. Thus the investigation offers immense scope for physicians and toxinologists to reinvestigate, design new strategies and think beyond the conventional mode of antivenom therapy.
蛇咬伤是一种被忽视的健康危害。其病理生理学主要集中在全身和局部毒性方面；然而，毒液和抗蛇毒血清诱导的氧化应激长期以来一直被忽视。抗蛇毒血清疗法虽然能中和毒液的致死性并挽救许多生命，但对氧化应激仍然无效。这促使我们用抗氧化分子褪黑素补充抗蛇毒血清，以预防氧化应激并提高现有蛇咬伤疗法的疗效。在此我们表明，在小鼠模型中，罗素蝰蛇和锯鳞蝰蛇的毒液会诱导强烈的氧化应激，即使在注射抗蛇毒血清后这种应激仍会持续。此外，抗蛇毒血清也会诱导氧化应激。多价抗蛇毒血清比单价抗蛇毒血清诱导的氧化应激更强。令人惊讶的是，抗蛇毒血清和褪黑素一起不仅能抑制毒液和抗蛇毒血清诱导的氧化应激，还能显著降低抗蛇毒血清的中和剂量。本研究为增强现有蛇咬伤疗法提供了治疗潜力。抗蛇毒血清 + 褪黑素的联合治疗将防止氧化应激的激增，并使抗蛇毒血清的用量最小化。因此，这项研究为医生和毒素学家重新研究、设计新策略以及突破传统抗蛇毒血清疗法的模式提供了广阔的空间。
