Propensity of crocin to offset Vipera russelli venom induced oxidative stress mediated neutrophil apoptosis: a biochemical insight

Abstract

Viper envenomation results in inflammation at the bitten site as well as target organs. Neutrophils and other polymorphonuclear leukocytes execute inflammation resolving mechanism and will undergo apoptosis after completing the task. However, the target specific toxins induce neutrophil apoptosis at the bitten site and in circulation prior to their function, thus reducing their number. Circulating activated neutrophils are major source of inflammatory cytokines and leakage of reactive oxygen species (ROS)/other toxic intermediates resulting in aggravation of inflammatory response at the bitten/target site. Therefore, neutralization of venom induced neutrophil apoptosis reduces inflammation besides increasing the functional neutrophil population. Therefore, the present study investigates the venom induced perturbances in isolated human neutrophils and its neutralization by crocin (Crocus sativus) a potent antioxidant carotenoid. Human neutrophils on treatment with venom resulted in altered ROS generation, intracellular Ca 2? mobilization, mitochondrial membrane depolarization, cyt-c translocation, caspase activation, phosphatidylserine externalization and DNA damage. On the other hand significant protection against oxidative stress and apoptosis were evidenced in crocin pre-treated groups. In conclusion the viper venom induces neutrophil apoptosis and results in aggravation of inflammation and tissue damage. The present study demands the necessity of an auxiliary therapy in addition to antivenin therapy to treat secondary/overlooked complications of envenomation.

Antiinflammatory, Antioxidant, and Immunomodulatory Effects ofCrocus sativusL. and its Main Constituents

“…Santhosh et al indicated that serum level of TNF‐α was also increased in rats after diazinon administration, which was significantly reduced in groups treated with diazinon plus α‐crocin 50 and 100 mg/kg. α‐Crocin also caused inhibitory effect on viper venom‐induced pro‐inflammatory cytokine, platelet, and neutrophil apoptosis (Santhosh et al ., ). This study demonstrated the anti‐ophidian property of α‐crocin, against viper venom‐induced oxidative stress.…”

“…In addition, venom‐induced apoptosis in isolated human neutrophils was also neutralized by α‐crocin. (Santhosh et al ., ).…”

“…It was indicated that α‐crocin prevented sesamol‐induced oxidative stress in platelets by modulating ROS production and thiol levels. It was reported that crocins ameliorated venom‐induced oxidative stress and hematological complications in serum of Swiss albino male mice (Santhosh et al ., ; Santhosh et al , ).…”

Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways

“…During the ARDS process, activated neutrophils release intracellular toxic components so as to amplify the inflammatory response by recruiting more inflammatory cells into the site of damage [34]. Additionally, Ma et al [35] reported that neutrophils were involved in regulating the microvascular endothelial permeability.…”

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

“…Thus, snakebite is a true example of a simultaneous lethal assault on vital systems and hence a dreadful medical emergency. In circulatory system, snake venoms not only affect vessel wall, platelet function, clot formation, and clot dissolution, but also target blood cells . Cells of the innate immunity, the white blood cells, are highly sensitive and take part in the venom‐induced inflammatory response, while red blood cells (RBCs) carry oxygen from lungs to tissues and H + from tissues to lungs to form carbon dioxide and water after reacting with HCO 3 ‐ and thus takes up the vital responsibility of gas transport in aerobic organisms.…”