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.
Bitis arietans venom (BAV) is known to cause various pathophysiological disorders by altering the cellular inclusions and enzymatic activities of different organs. Moringa oleifera leaf has been reportedly used for treatment of snake envenoming but there is no information on its neutralizing potentials against Bitis arietans venom. This study investigated the antivenin activity of ethanol crude extract of M. oleifera leaf on B. arietans envenomed rats and its inhibitory effects on some biological activities of the venom. The lethal dose (LD50) of BAV was estimated at 1.5 mg/kg−1. BAV induced various toxic effects in the in vivo study however, treatment with M. oleifera leaf extract (MOLE) ameliorated BAV-induced hypernatraemia and hypercalcemia. Acute anemia observed in untreated envenomed rats was reversed after treatment with various concentrations of MOLE with a significant (p < 0.05) dose dependent increase in hematological indices. Liver damage in untreated envenomed rats as indicated by higher concentration of serum liver enzymes and higher concentration of antioxidant enzymes were significantly (p < 0.05) decreased in MOLE treated rats. Also, BAV exhibited hemorrhagic, hemolytic and coagulating activities which were inhibited in a dose dependent manner by MOLE. A mild DNA fragmentation noticed in tissues of the heart of untreated envenomed rats was ameliorated in the MOLE treated rats. Results obtained in this study indicated that M. oleifera leaf have antivenin activity against B. arietans venom induced toxicities and underscores its use in folk medicine for the treatment of snake bites.
Echis ocellatus snakebite causes more fatalities than all other African snake species combined. Moringa oleifera reportedly possesses an antivenom property. Therefore, we evaluated the effectiveness of M. oleifera ethanol extract (MOE) against E. ocellatus venom (EOV) toxicities. Thirty male rats were grouped as follows (n = 5): Group 1 (normal control received saline), groups 2 to 6 were administered intraperitoneally, 0.22 mg/kg (LD50) of EOV. Group 2 was left untreated while group 3 to 6 were treated post-envenoming with 0.2 mL of polyvalent antivenom, 200, 400, and 600 mg/kg of MOE respectively. MOE significantly (p < 0.05) normalized the altered haematological indices and blood electrolytes profiles. MOE attenuated venom-induced cellular dysfunctions, characterized by a significant increase in NRF2, and concomitant downregulation of increased antioxidant enzymes (SOD and CAT) activities in the serum and heart of the treated rats. MOE normalized the elevated TNF-α and IL-1β in serum and heart tissues. Furthermore, the IgG titre value was significantly (p < 0.5) higher in the envenomed untreated group compared to the MOE-treated groups. Hemorrhagic, hemolytic and coagulant activities of the venom were strongly inhibited by the MOE dose, dependently. Lesions noticed on tissues of vital organs of untreated rats were abolished by MOE. Our findings substantiate the effectiveness of MOE as a potential remedy against EOV toxicities.
Envenoming by Echis ocellatus is potentially life-threatening due to severe hemorrhage, renal failure and capillary leakage. These effects are attributed to snake venom metalloproteinases (SVMPs). Due to drawbacks in the use of antivenin, natural inhibitors from plants are of interest in studies of new antivenin treatment. Antagonizing effects of bioactive compounds of Moringa oleifera is yet to be tested against SVMPs of E. ocellatus (SVMP-EO). Ethanol crude extract of M. oleifera was partitioned using n-hexane and ethyl acetate. Each partitions was fractionated using column chromatography and tested against SVMP-EO purified through ion exchange chromatography with EchiTab-PLUS polyvalent antivenin as control. Phytoconstituents of ethyl acetate fraction was screened against catalytic site of crystal of BaP1-SVMP while drug-likeness and ADMET toxicity of compound was equally determined. The molecular weight of isolated SVMP-EO was 43.28 kDa, with specific activity of 245 U/ml, percentage yield of 62.83 % and purification fold of 0.920. The Vmax and Km values are 2 mg/ml and 38.095 μmol/ml/min, respectively while the optimal pH and temperature are 6.0 and 40 °C, respectively. Polyvalent antivenin, crude extract and ethyl acetate fraction of M. oleifera exhibited complete inhibitory effect against SVMP-EO activity. Inhibitions of P-1 and P-II metalloprotease's enzymes by ethyl acetate fraction are largely due to methanol, 6, 8, 9-trimethyl-4-(2-phenylethyl)-3-oxabicyclo[3.3.1]non-6-en-1-yl)- and paroxypropione, respectively. Both compounds are potential drug candidates with little or no concern of toxicity as revealed from in-silico predictions. The inhibitory effects suggest that this compound might be therapeutic candidate for further exploration for treatment of Ocellatus' envenoming.