Zoology
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Item Influence of sex differences on renal and hepatic responses to sub-chronic arsenic exposure in albino rats(Faculty of Veterinary Medicine, University of Ibadan, 2020) Adeyi, O.E.; Adeyi, O.A.; Ibikunle, D.A.; Salami, A.J.; Dada, O.O.; Ayodele, A.P.; Oladimeji, O.AArsenic (As), a known carcinogen has been implicated in a variety of alterations in tissues. However, the influence of sex on toxicological response of key organs to arsenic exposure is poorly understood. This study was carried out to investigate the possible effects of inorganic arsenicals on hepatic and renal biomarkers in both male and female rats. Fifty rats divided into five groups of 10 animals (5 males and 5 females) were exposed to different doses of As either as sodium arsenite or sodium arsenate for five weeks. Activities of alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as concentrations of urea and creatinine were determined in plasma, liver and kidney tissues. Although the activities of all marker enzymes were increased in groups exposed to both arsenicals in a dose-dependent manner, the observed increase was more in groups exposed to arsenite salt. The extent of increase varied with sex. Male rats had a higher increase in ALP activities in all tissues, activities of tissue aminotransferases was more in the female groups while the male animals had more of these enzymes in the plasma on exposure to As. The 40 ppm arsenite salt elevated urea and creatinine concentrations in most tissues of both sexes.The liver architecture of both sexes was altered in a similar manner. These results indicate that sub-chronic exposure to As causes varying alterations in the marker enzymes of liver and kidney tissues in both sexes of albino rats.Item Kaempferol alleviates neurodegenerative disorders induced by Naja nigricollis venom via mechanisms of antioxidants, anti-inflammatory, dopaminergic and neuronal functions(Elsevier, 2024) Ajisebiola, B.S.; Mustapha, A-R.K.; Oyedara, O.O.; Oladele, J.O.; Adeyi, A.O."Naja nigricollis venom (NnV) contains neurotoxins that influence neurological functions. Kaempferol is a bioactive compound present in edible plants with numerous pharmacological activities. This study investigated the ameliorative potential of kaempferol against NnV-induced neurotoxicity in rats. Fifty male Wistar rats were randomized into five groups (n =10). Group 1 rats were the control while 1.0 mg/kg1 (LD50) of NnV was injected intraperitoneally into rats in groups 2–5 to observed neurotoxicity. Group 2 was untreated post en- venomation, while groups 3–5 were treated with polyvalent antivenom, 4 and 8 mg/kg of kaempferol, respec- tively. The biochemical analysis, neurotoxicity, and pathomorphological defects were assessed in the brain of the envenomed treated rats. Envenomation with NnV elevated oxidative and inflammatory biomarkers, and induced neurotoxicity accompanied with neurobehavioral deficits, and severe pathohistological defects were seen in the brain of untreated envenomed rats. However, treatment with kaempferol significantly (p <0.05) decreased malondialdehyde (MDA) levels and upregulated levels of reduce glutathione (GSH) antioxidant including su- peroxide dismutase (SOD) and glutathione peroxidase (GPX) antioxidant enzymes, while inflammatory bio- markers; nitric oxide (NO) levels and myeloperoxidase (MPO) activity significantly decreased in envenomed treated groups. Kaempferol upregulated dopamine concentration with significant suppression of acetylcholin- esterase (AchE) activity, and restored neurobehavioral and locomotor activities in envenomed treated rats. Also, severe pathomorphological alterations observed in the cortex of the brain were attenuated after kaempferol treatment. The underlaying ameliorative mechanisms of kaempferol are linked to its antioxidant activity, lipid peroxidation inhibition, anti-inflammatory activity, acetylcholinesterase suppression, and alleviation of dopa- mine system and neurobehavioral abilities."Item "Dabsylated Bradykinin Is Cleaved by Snake Venom Proteases from Echis ocellatus"(MDPI, 2024) Abiola, J.; Berg, A.M.; Aiyelaagbe, O.; Adeyi, A.; Konig, S.The vasoactive peptide bradykinin (BK) is an important member of the renin–angiotensin system. Its discovery is tightly interwoven with snake venom research, because it was first detected in plasma following the addition of viper venom. While the fact that venoms liberate BK from a serum globulin fraction is well described, its destruction by the venom has largely gone unnoticed. Here, BK was found to be cleaved by snake venom metalloproteinases in the venom of Echis ocellatus, one of the deadliest snakes, which degraded its dabsylated form (DBK) in a few minutes after Pro7 (RPPGFSP↓FR). This is a common cleavage site for several mammalian proteases such as ACE, but is not typical for matrix metalloproteinases. Residual protease activity < 5% after addition of EDTA indicated that DBK is also cleaved by serine proteases to a minor extent. Mass spectrometry-based protein analysis provided spectral proof for several peptides of zinc metalloproteinase-disintegrin-like Eoc1, disintegrin EO4A, and three serine proteases in the venom.Item Kaempferol mitigates reproductive dysfunctions induced by Naja nigricollis venom through antioxidant system and anti‑inflammatory response in male rats(Nature Portfolio / Springer Nature, 2024) Adeyi, A.O.; Ajisebiola, B.S.; Sanni, A.A.; Oladele, J.O.; Mustapha, A-R.K.; Oyedara, O.O.; Fagbenro, O.S.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 NnVinduced 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.Item Biosynthesis, characterization and antivenom activities of Moringa oleifera silver nanoparticles: an experimental approach(Zoological Society of Nigeria, 2023) Adeyi, A.O.; Olowookorun, T.O.; Ajisebiola, B.S.; Labulo, H.A.; Adeyi, O.E.; Ibrahim, H.Moringa oleifera has been previously established to possess neutralizing potentials against Echis ocellatus venom. This study however, investigated the bioefficacy of silver nanoparticles biosynthesized from M. oleifera leaf extract aimed at improving its bioactivity against E. ocellatus venom-induced toxicities using in vivo and in vitro methods. The intrinsic characteristics of the produced M. oleifera-Silver nanoparticles (MO-AgNPs) were carried out using energy dispersive X-ray, X-ray diffraction, scanning electron microscopy, transmission electron microscopy and Fourier-transform infrared spectroscopy. Twenty-five male Wistar rats divided randomly into five groups (n=5) were used for the antivenom study. Group 1 received saline while groups 2 to 5 were envenomed intraperitoneally with 0.22mg/kg (LD50) of E. ocellatus venom. Group 2 was left untreated while groups 3 to 5 were treated with 0.2ml of antivenom, 5 and 10mg/kg MO-AgNPs post-envenomation, respectively. Blood and tissue of treated rats were analyzed for heamatological parameters and histopathology, respectively. The MO-AgNPs formation was confirmed with a colour change from light brown to yellowish-brown with maximum SPR band at 420nm from UV-Vis analysis, indicating a reflection of the bio-reduction of Ag+ to Ag0. The Transmission electron micrographs showed well dispersed spherical AgNPs with average particle size of 15.7nm. Treatment with MO-AgNPs caused a significant improvement of acute anemia, leucopenia and thrombocytopenia induced by the venom in the envenomed treated rats. Also, MO-AgNPs inhibited the haemorrhagic, haemolytic and anticoagulant activities of the venom. Tissue lesions observed in heart of envenomed untreated rats were attenuated after treatment with MO-AgNPs. The biosynthesized MO-AgNPs exhibited potent neutralizing potentials than M. oleifera crude extract against E. ocellatus venom toxicities.Item "Inhibition of Metalloproteinase from Bitis arietans Venom In Vitro by the Ethyl Acetate Fraction of Moringa oleifera and Its Chemical Profile"(Springer Nature, 2023) Ajisebiola, B.S.; Bello, F.T.; Osamudiamen, P.M.; Oladele, J.O.; Adeyi, A.O.Moringa oleifera Lam., Moringaceae, ethyl acetate soluble fraction has been documented to contain bioactive antivenom chemicals against Bitis arietans venom toxicities. Snake venom metalloproteinase is the principal enzyme of B. arietans venom exhibiting severe haemorrhage and haemostatic disturbances in envenomed victims. In this current study, B. arietans snake venom metalloproteinase was isolated using ion-exchange chromatography and gel filtration while SDS-PAGE was used to determine enzyme molecular weight. M. oleifera ethyl acetate soluble fraction was fractionated using column and thin-layer chromatography into subfractions and tested against B. arietans snake venom metalloproteinase. EchiTab polyvalent antivenom was used as the standard drug. The compounds present in the most active subfraction were identified using GCMS. The molecular weight of isolated enzyme was 43.28 kDa with specific activity of 3.06 μmol/min/mg and percentage yield of 18.5%. A total of 8 subfractions were obtained after fractionation and labelled ethyl acetate subfractions F1-8. All subfractions showed significant (p < 0.05) inhibition against B. arietans snake venom metalloproteinase activity. However, subfraction F5 demonstrated the highest inhibition against B. arietans snake venom metalloproteinase activity with total inhibition at all concentrations compared to other subfractions and antivenom. Subfraction F5 displayed substantial inhibition against the haemorrhagic, haemolytic, and anticoagulant activities of B. arietans venom with a dose-dependent effect. The major bioactive compounds of subfraction F5 were γ-sitosterol (5.92%), kaempferol (5.9%), quercetin (5.28%), n-hexadecanoic acid (5.23%), and n-pentacosane (5.22%) of which some were previously reported as potential snake venom inhibitors. Results showed that subfraction F5 possesses potential antivenom compounds that could be explored for snakebite treatment.Item Ferulic acid mitigates 2-methoxyethanol-induced testicular oxidative stress via combined downregulation of FoxO1, PTEN, and modulation of Nrf2-Hmox1-NQO1 signaling pathway in rats(Elsevier, 2023) Adeyi, O.E.; Somade, O.T.; James, A.S.; Adeyi, A.O.; Ogbonna-Eze, S.N.; Salako, O.Q; Makinde, T.V.; Ajadi, O.M.; Nosiru, S.A.INTRODUCTION: Ferulic acid (FERA) is a natural antioxidant that is richly found in herbs, including Ligusticum chuangxiong, Cimicifuga heracleifolia, and female ginseng (Angelica sinensis), which are utilized in modern Chinese medicine, and in cereals/grains including rice, which is mostly consumed by humans. 2METE on the other hand, is a ubiquitous substance that has many industrial applications, including use in the preparation of dyes for textiles, hydraulic fluid for automobiles, paints, and liquid soaps. It is a testicular toxin, which can induce oxidative stress in the testis of rats. Therefore, this study investigated the effect of FERA, which was concomitantly administered, against 2-methoxyethanol (2METE)-induced testicular oxidative stress in rats. METHODS: Male Wistar rats totaling twenty (20), separated into four (4) groups, were used for the study. Rats in group one served as the control, rats in groups two and three were administered 100 mg/kg of 2METE only for 30 consecutive days, but only rats in group three were concomitantly treated with 50 mg/kg of FERA for the same duration, while rats in group four were treated with 50 mg/kg of FERA only. RESULTS: Following analysis, 2METE administration caused a significant reduction in the relative testes weight (RTW), NAD(P)H quinone oxidoreductase 1 (NQO1), and reduced glutathione (GSH) levels, as well as superoxide dismutase (SOD) and glutathione S-transferase (GST) activities in the testis of rats compared with the control. Moreover, 2METE administration also significantly increased the testicular levels of malondialdehyde (MDA), nitric oxide (NO), and RNA gene expressions of heme oxygenase 1 (Hmox1), nuclear factor erythroid 2-related factor 2 (Nrf2), forkhead box protein O1 (FoxO1), and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) compared with the control. FERA treatment, on the other hand, significantly decreased the testicular levels of MDA, as well as Nrf2, Hmox1, PTEN, and FoxO1 gene expressions, and significantly increased the testic- ular GSH and NQO1 levels, activities of GST, SOD, glutathione peroxidase (GPx), and catalase (CAT) compared with 2METE only administered rats. CONCLUSION: 2METE-induced testicular oxidative stress, marked by the depletion of the endogenous antioxidant systems, was recorded, which resulted in the activation of PTEN, FoxO1, and Nrf2 genes in rats. FERA demon- strated a strong antioxidant effect by restoring the levels and activities of the endogenous antioxidants as well as downregulating the expressions of PTEN, FoxO1, and Nrf2 in the testis of rats.Item "Inhibition of phospholipase A2 from Naja haje and Naja nigricollis venoms by active fraction of Moringa oleifera leaves: in vitro and in silico methods"(Taylor & Francis, 2023) Adeyi, A.O.; Jimoh, A.O.; Ajisebiola, B.S.; Adeyi, O.E.; Metibemu, D.S.; Okonji, P.E.Phospholipases are one of the principal toxic enzymes in snake venoms inducing a wide variety of pharmacological effects after envenomation. Natural inhibitors from plants are known to inhibit the toxic enzyme activities of snake venoms. In this study, ethanol crude extract of M. oleifera leaves was partitioned using n-hexane and ethyl acetate after which fractionation was done using column and thin layer chromatography. Subsequently, the inhibitory activities of the crude extract and sub-fractions of M. oleifera were investigated against phospholipases A2 isolated from Naja haje and Naja nigricollis venoms using in vitro and in-silico approaches while EchiTab-PLUS polyvalent antivenom was used as the standard drug. The molecular weight of isolated N. haje phospholipase A2 (NH-PL) and N. nigricollis phospholipase A2 (NN-PL) were 24.11 and 35.22 kDa respectively. NH-PL enzyme had a specific activity of 2.70 lM/min/mg substrate while NN-PL activity was 2.10 lM/min/mg substrate. The Km of NH-PL was 0.330 lM with Vmax of 0.085 lM/mL min while NN-PL had Vmax of 0.198 lM/mL.min and Km of 0.670 lM. M. oleifera nhexane sub-fraction 5 (MOLH5) exhibited a total inhibition of NN-PL and NH-PL enzyme activities at all concentrations used. Molecular docking of the phytoconstituents of MOLH5 against the catalytic site of phospholipase A2 revealed 2-Hydrazino-8-hydroxy-4-phenylquinoline as the lead compound and a potential drug candidate with a docking score of _6.789 kcal/mol. Findings indicated that MOLH5 possesses phospholipase A2 natural inhibitors that could be explored as a therapy for snake envenoming.Item Syringic acid demonstrates better anti-apoptotic, anti-inflammatory and antioxidative effects than ascorbic acid via maintenance of the endogenous antioxidants and downregulation of pro-inflammatory and apoptotic markers in DMN-induced hepatotoxicity in rats(Elsevier, 2023) Adeyi, O.E.; Somade, O.T.; Ajayi, B.O.; James, A.S.; Adeyi, A.O.; Olayemi, Z.M.; Tella, N.B.Dimethyl nitrosamine (DMN) is a known hepatotoxin, carcinogen, and mutagen. This study is therefore carried out to investigate the therapeutic effects of syringic acid (SYRA) and ascorbic acid (ASCA) in DMN-induced hepatic injury in rats. Following DMN administrations, malondialdehyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) as well as activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) were significantly increased. Also significantly increased were levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Following treatment with SYRA and ASCA, the activities of ALT, AST, GPx, CAT and SOD, as well as MDA, GSH, TNF-α, IL-1β, and NFkB levels were significantly reduced. Overall, both treatments were effective, but SYRA had a better therapeutic effect than ASCA. Therefore, this promising potential of SYRA can be taken advantage of in the treatment of DMN-induced hepatic injury.Item "Ethyl Acetate Fraction of Moringa oleifera Leaves Mollified Toxicological Activities Actuated by Bitis arietans (Puff adder) Venom"("Faculty of Physical Sciences and Faculty of Life Sciences, Univ. of Ilorin, Nigeria", 2022) Ajisebiola, B.S.; Oyinlola, R.R.; Akintunde, S.O.; Paul, O.; Adeyi, A.O.Bitis arietans (Puff adder) venom possess numerous biological active toxins exhibiting toxicological actions after envenoming. Moringa oleifera crude extract has been documented to extenuate toxicities induced by B. arietans venom. This study reported the efficacy of n-hexane, ethyl acetate and ethanol solvent fractions obtained from crude extract of M. oleifera against the lethal dose toxicity, biological activities and oxidative stress induced by B.arietans venom to ascertain the best fraction with active antivenom phytochemicals. Forty-five male rats were randomly selected into nine groups (n=5) for the anti-oxidative stress study. Groups 1 served as control; group 2 to 9 were envenomed by a single intraperitoneal injection of 1.5 mg/kg (LD50) of the venom. Group 2 was not treated post envenomation while groups 3 was treated with polyvalent antivenom. Group 4, 6 and 8 were treated with 300 mg/kg while group 5, 7 and 9 were treated with 600 mg/kg of n-hexane, ethyl acetate and ethanol solvent fractions of M. oleifera respectively. High dose of M. oleifera ethyl acetate solvent fraction best neutralized the lethal dose toxicity and strongly inhibited the heamorrhagic and anticoagulant activities of B. arietans venom. The venom induced oxidative stress with significant (P<0.05) enhancement of Superoxide Dismutase, Catalase and Malondialdehyde levels in serum and heart tissues of untreated envenomed rats. However, ethyl acetate solvent fraction was most effective in normalizing the antioxidant enzyme activities of envenomed treated rats. Results showed that ethyl acetate fraction of M. oleifera possesses active antivenom phytochemicals against B. arietans venom induced toxicities.
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