Melatonin alleviates Echis carinatus venom‐induced toxicities by modulating inflammatory mediators and oxidative stress

Abstract

Viper bites cause high morbidity and mortality worldwide and regarded as a neglected tropical disease affecting a large healthy population. Classical antivenom therapy has appreciably reduced the snakebite mortality rate; it apparently fails to tackle viper venom-induced local manifestations that persist even after the administration of antivenom. Recently, viper venom-induced oxidative stress and vital organ damage is deemed as yet another reason for concern; these are considered as postmedicated complications of viper bite. Thus, treating viper bite has become a challenge demanding new treatment strategies, auxiliary to antivenin therapy. In the last decade, several studies have reported the use of plant products and clinically approved drugs to neutralize venom-induced pharmacology. However, very few attempts were undertaken to study oxidative stress and vital organ damage. Based on this background, the present study evaluated the protective efficacy of melatonin in Echis carinatus (EC) venom-induced tissue necrosis, oxidative stress, and organ toxicity. The results demonstrated that melatonin efficiently alleviated EC venom-induced hemorrhage and myonecrosis. It also mitigated the altered levels of inflammatory mediators and oxidative stress markers of blood components in liver and kidney homogenates, and documented renal and hepatoprotective action of melatonin. The histopathology of skin, muscle, liver, and kidney tissues further substantiated the overall protection offered by melatonin against viper bite toxicities. Besides the inability of antivenoms to block local effects and the fact that melatonin is already a widely used drug promulgating a multitude of therapeutic functionalities, its use in viper bite management is of high interest and should be seriously considered.

Oxidative stress‐induced methemoglobinemia is the silent killer during snakebite: a novel and strategic neutralization by melatonin

“…In in vivo studies, the administration of melatonin along with antivenom significantly reduced the Nn venom‐induced oxidative stress and as well as inflammatory markers. This is in line with our earlier study carried out in the recent past, where the melatonin effectively reduced the E. carinatus venom‐induced toxicity by modulating inflammatory mediators and oxidative stress . In pre‐incubation experiments, the administration of melatonin alone not only increased the survival time of Nn venom‐injected mice but also offered complete protection when administered in combination with half effective dose of antivenom (group VI), while antivenom alone offered complete protection at effective dose (group IV).…”

Protective effects of melatonin against oxidative damage induced by Egyptian cobra (Naja haje) crude venom in rats

“…It also mitigates the oxidative stress and vital organ damage induced by venom of the viper Echis carinatus in mice (Katkar et al, 2014). Because of the previously reported protective effects of melatonin against venom from a variety of sources, we investigated whether melatonin would be effective against N. haje venom-induced toxicity in the liver, kidneys, and heart of rats.…”

Melatonin alleviates cadmium‐induced liver injury by inhibiting the TXNIP‐NLRP3 inflammasome

“…Melatonin ( N ‐acetyl‐5‐methoxytryptamine), an indoleamine, is synthesized by the pineal gland and also produced by peripheral organs such as retina, Harderian gland, gut, and skin . Melatonin has been shown to exert biological activities, including antioxidative, anti‐inflammatory, and anti‐apoptotic properties . Previous studies have demonstrated that melatonin exhibits powerful hepatoprotective effects in a series of liver injury models, including ischemia/reperfusion, viral hepatitis, liver fibrosis, and heavy metal‐induced liver injury .…”