Therapeutic potency of kaempferol against Naja haje venom induced neurotoxicity, inflammation, biological activities, and antioxidant system damage: a pre-clinical antivenom evaluation

Abstract

Naja haje envenoming manifests organ system disorders leading to severe fatalities due to the venom's toxins. The neutralizing capacity of kaempferol has been reported against some medically significant snake venoms with exception of N. haje venom (NhV). This current study assessed the neutralizing profile of kaempferol against toxicities induced by NhV using in vitro and in vivo methods. In in vitro, NhV induced wide spectrum of toxic biological activities with substantial increase in hemorrhagic, anticoagulating, and hemolytic effects. Likewise in the in vivo study, the venom caused hematological disorders by inducing acute anemia, thrombocytopenia, and leucopenia in envenomed rats. Also, the venom caused detrimental effect on the antioxidant defense system of the brain through significant (P < 0.05) elevation of malondialdehyde (MDA), nitrite (NIT), and suppression of reduce glutathione (GSH) antioxidant, superoxide dismutase (SOD), catalase (CAT), and glutathione transferase (GST) enzymes. Additionally, the levels of neurotoxicity biomarkers, monoamine oxidase (MAO) and acetylcholinesterase (AChE), and pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were significantly (P < 0.0.5) enhanced by NhV in the brain of envenomed rats. Severe pathohistological effects were observed in brain tissues of the envenomed rats. However, kaempferol substantially (P < 0.05) inhibited the NhV-induced biological activities, normalized the hematological disorders, enhanced antioxidants system functions, and significantly (P < 0.05) suppressed the levels of neurotoxicity biomarkers and pro-inflammatory cytokines. Severe structural alterations observed in the brain tissues were ameliorated after kaempferol treatment. Further exploration of kaempferol could lead to the development of an alternative therapy for treatment of N. haje envenoming.