Kaempferol mitigates reproductive dysfunctions induced by Naja nigricollis venom through antioxidant system and anti-inflammatory response in male rats.

Naja nigricollis Venom (NnV) contains complex toxins that affects various vital systems functions after envenoming. The venom toxins have been reported to induce male reproductive disorders in envenomed rats. This present study explored the ameliorative potential of kaempferol on NnV-induced male reproductive toxicity. Fifty male wistar rats were sorted randomly into five groups (n = 10) for this study. Group 1 were noted as the control, while rats in groups 2 to 5 were injected with LD50 of NnV (1.0 mg/kg bw; i.p.). Group 2 was left untreated post envenomation while group 3 was treated with 0.2 ml of polyvalent antivenom. Groups 4 and 5 were treated with 4 and 8 mg/kg of kaempferol, respectively. NnV caused substantial reduction in concentrations of follicle stimulating hormone, testosterone and luteinizing hormone, while sperm motility, volume and counts significantly (p < 0.05) decreased in envenomed untreated rats. The venom enhanced malondialdehyde levels and substantially decreased glutathione levels, superoxide dismutase and glutathione peroxidase activities in the testes and epididymis of envenomed untreated rats. Additionally, epididymal and testicular myeloperoxidase activity and nitric oxide levels were elevated which substantiated severe morphological defects noticed in the reproductive organs. However, treatment of envenomed rats with kaempferol normalized the reproductive hormones with significant improvement on sperm functional parameters. Elevated inflammatory and oxidative stress biomarkers in testis and epididymis were suppressed post kaempferol treatment. Severe histopathological lesions in the epididymal and testicular tissues were ameliorated in the envenomed treated groups. Results highlights the significance of kaempferol in mitigating reproductive toxicity induced after snakebite envenoming.

Kaempferol from Moringa oleifera demonstrated potent antivenom activities via inhibition of metalloproteinase and attenuation of Bitis arietans venom-induced toxicities.

Bitis arietans venom (BAV) can induce severe pathophysiological disorders after envenoming. However, studies have shown that the Moringa oleifera fraction is effective against BAV toxicities and contains bioactive compounds with significant antivenom potency. This research aimed to identify the main active antivenom compound in the M. oleifera fraction responsible for neutralizing the toxicities induced by BAV. The compounds identified from M. oleifera fraction were docked in silico against the catalytic site of the Snake Venom Metalloproteinase (SVMP) to determine the lead inhibitor compound. The antivenom potency of the lead inhibitor compound was tested against BAV toxicities and metalloproteinase isolated from BAV using in vitro and in vivo methods, while EchiTab-Plus polyvalent antivenom served as a standard drug. The in silico prediction revealed kaempferol as the lead inhibitor compound with a docking score of -7.0 kcal/mol. Kaempferol effectively inhibited metalloproteinase activity at 0.2 mg/ml, compared to antivenom (0.4 mg/ml) and demonstrated significant antihaemorrhagic, antihaemolytic and coagulant effects against BAV activities. Furthermore, kaempferol showed a significant dose-dependent effect on altered haematological indices observed in rats challenged with LD50 of BAV. Envenomed rats also showed an increase in oxidative stress biomarkers and antioxidant enzyme activity in the heart and kidney. However, treatment with kaempferol significantly (P < 0.05) decreased malondialdehyde levels and SOD activity with concomitant enhancement of glutathione levels. Severe histopathological defects noticed in the organ tissues of envenomed rats were ameliorated after kaempferol treatment. Kaempferol is identified as the main active antivenom compound in M. oleifera, and this research highlights the potential of the compound as an effective alternative to snakebite treatment.

Echis ocellatus Venom-Induced Reproductive Pathologies in Rat Model; Roles of Oxidative Stress and Pro-Inflammatory Cytokines.

This study reported reproductive pathologies associated with Echis ocellatus venom in animal model. Twenty male Wistar rats with body weight between 180 and 220 g were selected randomly into two groups (n = 10). Rats in group 1 served as the control while rats in group 2 were envenomed with a single intraperitoneal injection of 0.055 mg/kg−1 (LD6.25) of E. ocellatus venom on the first day and a repeated dose on the twenty fifth day. Both control and envenomed rats were monitored for fifty consecutive days. The venom caused a significant (p < 0.05) reduction in sperm motility, count, and volume, with increased sperm anomalies in envenomed rats compared to the control. Likewise, serum concentrations of male reproductive hormones were significantly (p < 0.05) higher in envenomed rats. Increased levels of malondialdehyde were accompanied by a significant (p < 0.05) decrease in reduced glutathione and catalase activity in the epididymis and testis tissues of envenomed rats. The venom enhanced the release of epididymal and testicular tumor necrosis factor-alpha and interleukin1-beta compared to the control. Furthermore, severe pathological defects were noticed in tissues of the testis and epididymis of envenomed rats. This study demonstrated that E. ocellatus venom toxins can induce reproductive dysfunction in male victims of snake envenoming.

Naja nigricollis venom altered reproductive and neurological functions via modulation of pro-inflammatory cytokines and oxidative damage in male rats.

Reproductive and neurological anomalies are often characterized by malfunctioning of reproductive and nervous organs sometimes attributed to systemic toxins. However, limited information is available on the impact of snake venom toxins on male reproductive and nervous system. This study investigated the toxicological effects of Naja nigricollis venom on male reproductive and neural functions in rat model. Twenty male Wistar rats weighing between 195 and 230 g were divided randomly into two groups of ten rats each. Group 1 served as normal control while rats in group 2 were envenomed with a single intraperitoneal injection of 0.25 mg/kg-1 (LD12.5) of N. nigricollis venom on first and twenty fifth day within the period of fifty days experiment. The venom significantly decreased sperm counts, motile cells and volume combined with increased sperm abnormalities. The venom induced hormonal imbalances in the envenomed group as levels of testosterone, luteinizing and follicle stimulating hormones depreciated compared to the control. Oxidative stress biomarkers: malondialdehyde significantly increased parallels with depletion of glutathione level and catalase activities in testis, epididymis and brain of envenomed rats. Furthermore, N. nigricollis venom up-regulated tumor necrosis factor-alpha (TNF-α) and interleukin1-beta (IL-1ß) production in testis, epididymis and brain of envenomed rats compared to the control. Also, various histological alterations were noticed in tissues of testis, epididymis and brain of envenomed rats. Findings indicated that N. nigricollis venom is capable of inducing reproductive and neurological dysfunction in envenomed victims.

Moringa oleifera leaf fractions attenuated Naje haje venom-induced cellular dysfunctions via modulation of Nrf2 and inflammatory signalling pathways in rats.

Naja haje envenoming could activate multiple pathways linked to haematotoxic, neurological, and antioxidant systems dysfunctions. Moringa oleifera has been used in the management of different snake venom-induced toxicities, but there is no scientific information on its antivenom effects against Naja haje. This study thus, investigated the antivenom activities of different extract partitions of M. oleifera leaves against N. haje envenoming. Forty five male rats were divided into nine groups (n = 5). Groups 2 to 9 were envenomed with 0.025 mg/kg (LD50) of N . haje venom while group 1 was given saline. Group 2 was left untreated, while group 3 was treated with polyvalent antivenom, groups 4, 6 and 8 were treated with 300 mg/kg-1 of N-hexane, ethylacetate and ethanol partitions of M. oleifera, respectively. Groups 5, 7 and 9 were also treated with 600 mgkg-1of the partitions, respectively. Ethanol extract and ethyl acetate partition of M. oleifera significantly improved haematological indices following acute anaemia induced by the venom. Likewise, haemorrhagic, haemolytic and anti-coagulant activities of N. haje venom were best inhibited by ethanol partition. Envenoming significantly down-regulated Nuclear factor erythroid 2-related factor 2 (Nrf2) with the consequent elevation of antioxidant enzymes activities in the serum and brain. Treatment with extract partitions however, elevated Nrf2 levels while normalising antioxidant enzyme activities. Furthermore, there were reduction in levels of pro-inflammatory cytokines (TNF-α and interleukin-1ß) in tissues of treated envenomed rats. This study concludes that ethanol partition of M. oleifera was most effective against N. haje venom and could be considered as a potential source for antivenom metabolites.