Faculty of Basic Medical Sciences
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Browsing Faculty of Basic Medical Sciences by Author "Otuechere, Chiagoziem"
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- ItemThe Anti-Parasite Action of Imidazole Derivatives Likely Involves Oxidative Stress but not HIF-1α Signaling.(Elsevier, 2021-11-01) Otuechere, ChiagoziemBackground: Therapeutic options for toxoplasmosis are limited. This fact underscores ongoing research efforts to identify and develop better therapy. Previously, we reported the anti-parasitic potential of a new series of derivatives of imidazole. Objective: In the current investigation, we attempted the investigation of the possible action mechanism of few promising anti-parasite imidazole derivatives namely C1 (bis-imidazole), C2 (phenyl-substituted 1H-imidazole) and C3 (thiophene-imidazole) Methods: We evaluated if oxidative stress, hypoxia as well as metabolic reprogramming of host L-tryptophan pathway form part of the parasite growth inhibition by imidazoles. Anti-parasite assay was performed for imidazoles at concentrations ranging from 0 to 10 μM, while pyrimethamine was used as reference drug to validate assay. Results: Imidazole compounds restricted parasite growth dose-dependently. However, in the presence of an antioxidant (Trolox), L-tryptophan and/or CoCl2 (chemical inducer of hypoxia), the growth inhibitory efficacy of imidazoles was appreciably abolished. Further, imidazole treatment led to elevated level of reactive oxygen species, while reducing parasite mitochondrial membrane potential compared with control. In contrast, imidazole had no effect on host HIF-1α level suggesting its exclusion in the anti-parasite action. Conclusion: Taken together, imidazole-based compounds might restrict parasite growth by causing oxidative stress. The findings provide new insight on the likely biochemical mechanisms of imidazoles as prospective antiparasite therapy. Data gives new perspective that not only underscores the anti-parasite prospects of imidazoles, but implicates the host L-tryptophan pathway as a feasible treatment option for T. gondii infections.
- ItemAtherogenic Index and Lipid Profiles in Albino Rats Fed with Surface Modified Hibiscus sabdariffa Cellulose(Elsevier, 2021-11) Otuechere, ChiagoziemDespite the several applications of modified cellulose, there is limited information on their safety, and antidyslipidemic functions, which are the focus of this study. To address this, cellulose isolated from Hibiscus sabdariffa cellulose was surface modified using nitrilotri- acetic acid to produce nitrilotriacetic acid modified Hibiscus sabdariffa cellulose (HSNT). It was characterized using Fourier transformed infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric (TGA) analysis, scanning electron microscopy (SEM) and carbon, hydrogen, nitrogen, sulfur/oxygen (CHNS/O) analyzer. The study further investigated the safety of HSNT at the doses of 50, 100, and 150 mg kg−1 body weight in albino rats after a 7-day uninterrupted oral gavage. Histology of cardiac and hepatic tissues was observed, in addition to estimation of clinico-biochemical parameters such as atherogenic index of plasma (AIP), Castelli’s risk index (CRI-1), total cholesterol, high-density lipoprotein choles- terol (HDL-C), triglyceride (TG), albumin (ALB), aspartate aminotransferase (AST) and ala- nine aminotransferase (ALT). FTIR revealed peaks corresponding to the synthesis of HSNT, while XRD showed HSNT to have a crystallinity index of 53.20% with a type I cellulose crystal. HSNT had no significant effect on the absolute heart and liver weights, heart and liver organo-somatic indices, TG, AST, and ALB. Exposure to HSNT-50 caused a significant decrease in AIP levels. However, administration of HSNT-100 and 150 significantly reduced ALT, total cholesterol, and CRI-1 levels but caused a significant elevation in HDL-C lev- els. Cardiac histology revealed mild inflammatory and fatty infiltration of the myocardium, while the significant indications of the hepatic morphology included congestion of vessels and mild focal periportal infiltration at the HSNT-100 and HSNT-150 doses. Our preliminary data seem to indicate the potential of HSNT modification to resolve blood lipid abnormal- ities and make a case for an expanded study on its cardio-hepatic effects as well as study to understand the causes of congestion in hepatic vessels
- ItemEvaluation of the Hepato-Renal Functions and Antimicrobial Activity of Fatty Amido Benzoic Acid Synthesised from Citrullus colocynthis Seed Oil.(SpringerOpen, 2021-01-18) Otuechere, ChiagoziemRapid progression in resistance to antimicrobial agents by pathogenic organisms is a serious concern. This study aimed to synthesize fatty amido benzoic acid (FBA) from Citrullus colocynthis seed oil (CCO) and evaluate its safety profile as an alternative bioactive agent for combating drug-resistant pathogens. FBA was synthesised through simple chemical reaction route and examined for its antioxidant activity and antimicrobial capacity against selected drug-resistant microorganisms. Effect of FBA on hepato-renal function makers and oxidative stress was also examined using Wistar rats. Density functional theory (DFT) approach was employed to understand the action of FBA with the aid of lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO). Gas Chromatography (GC) revealed the most abundant fatty acid in CCO to be C18:2 (55.88%). Results from Fourier transformed infrared spectroscopy (FTIR), and proton nuclear magnetic resonance (1HNMR) confirmed the synthesis of FBA with a yield of 97.10%. FBA exhibited antioxidant potential (IC50 of 1.96 µg mL−1) as well as antimicrobial potency. Minimum inhibitory concentration (MIC) of FBA was 0.026 mg mL−1. Biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, hydrogen peroxide, and lipid peroxidation were significantly elevated in rats administered high dose FBA (100 mg kg−1). Histology of the liver and kidney confirmed the biochemical results. Furthermore, mechanism of action of FBA could be described by quantum chemical analysis to be via nucleophilic interaction, which may be viewed electronically as donor–acceptor interaction. The study presents FBA as a promising antimicrobial agent for combating drug-resistant pathogenic organisms.
- ItemGreen Synthesized Zinc Oxide Nanoparticles Elicited a Prominent Suppression of Oxidative and Inflammatory Distortions in Rats Exposed To Carbon Tetrachloride(Biointerface Research in Applied Chemistry, 2021-10-18) Otuechere, ChiagoziemThis study centered on Zinc oxide nanoparticles capped with Pterocarpus mildbraedii leaf extracts (PmZnONPs) as a potent antioxidant and anti-inflammatory agent against carbon tetrachloride (CCl4) ‐ induced hepatorenal toxicity in rats. PmZnONPs were characterized by Fourier transform infrared spectroscopy (FTIR), Brunauer–Emmett–Teller (BET), scanning electron microscopy (SEM), X-ray diffraction pattern (XRD), and transmission electron microscopy (TEM) techniques. The FTIR results revealed the presence of various functional groups in PmZnONPs, while the BET showed a surface area of 1.55 mg-2. In vitro, PmZnONPS showed comparable 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH), and 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid (ABTS) radicals scavenging activities as Vitamin C. After that, PmZnONPs (1 and 3 mg/kg) were administered (p.o.) into six groups of rats, using CCl4 as the toxicant. The obtained results demonstrated that PmZnONPS significantly prevented CCl4‐induced elevations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma‐glutamyl transferase (GGT), alkaline phosphatase (ALP), bilirubin (BIL), creatinine, and urea. Moreover, PmZnONPs restored the levels of plasma uric acid, hepatorenal antioxidant enzymes, including superoxide dismutase, glutathione peroxidase, glutathione transferase, and glutathione that were significantly decreased by CCl4 treatment. Immunohistochemical studies showed that PmZnONPs significantly suppressed the high immunoreactivity of nuclear factor kappa B (NF‐κB), cyclooxygenase‐2 (COX-2), and interleukin‐6 (IL-6) arising from CCl4 intoxication. Thus our data hint that PmZnONPs suppressed CCl4‐induced toxicity in the liver and kidney of rats via its combined antioxidant and anti‐inflammatory properties.
- ItemHypoxia and the Kynurenine Pathway: Implications and Therapeutic Prospects in Alzheimer’s Disease.(Hindawi, 2021-11-10) Otuechere, ChiagoziemNeurodegenerative diseases (NDs) like Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson’s disease, and Huntington’s disease predominantly pose a significant socioeconomic burden. Characterized by progressive neural dysfunction coupled with motor or intellectual impairment, the pathogenesis of ND may result from contributions of certain environmental and molecular factors. One such condition is hypoxia, characterized by reduced organ/tissue exposure to oxygen. Reduced oxygen supply often occurs during the pathogenesis of ND and the aging process. Despite the well-established relationship between these two conditions (i.e., hypoxia and ND), the underlying molecular events or mechanisms connecting hypoxia to ND remain ill-defined. However, the relatedness may stem from the protective or deleterious effects of the transcription factor, hypoxia-inducible factor 1-alpha (HIF-1α). The upregulation of HIF-1α occurs in the pathogenesis of most NDs. The dual function of HIF-1α in acting as a “killer factor” or a “protective factor” depends on the prevailing local cellular condition. The kynurenine pathway is a metabolic pathway involved in the oxidative breakdown of tryptophan. It is essential in neurotransmission and immune function and, like hypoxia, associated with ND. Thus, a good understanding of factors, including hypoxia (i.e., the biochemical implication of HIF-1α) and kynurenine pathway activation in NDs, focusing on Alzheimer’s disease could prove beneficial to new therapeutic approaches for this disease, thus the aim of this review.
- ItemPolyathia longifolia: Redox Potential of a Cellulose Nanocrystal Derivative and ADMET Predictions of Selected Compounds.(Biocatalysis and Agricultural Biotechnology, 2022-03) Otuechere, ChiagoziemCellulosic biomass, endowed with several hydroxyl groups, has been the source of nanomaterials and functionalized derivatives for biomedical applications. However, the effect of green-synthesized cellulose nanocrystals from Polyathia longifolia (PCN) on redox parameters in the rat cortex and cerebellum has not been evaluated. In the present study, eighteen male albino rats were randomly grouped as control, PCN-50 and PCN-100, and administered distilled water, 50, and 100 mg/kg body weight PCN once a day (per os) for 14 consecutive days. Growth performance, biochemical, histological analyses were performed to monitor treatment-related parameters. PCN, at both doses, did not significantly (p > 0.05) alter the body weights, absolute organ weights, albumin, cortical and cerebellar catalase, and glutathione S-transferase levels. However, PCN significantly elevated aspartate aminotransferase, cortical and cerebellar glutathione, and lipid peroxidation levels. Interestingly, histological observations revealed normal-appearing neurons, hippocampus, and Purkinje layers. Furthermore, in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of nine ligands from Polyalthia longifolia established oral drug-like behavior. They showed 5-hydroxy-2 (5H)-furanone as the safest compound among all selected ligands. Our data provide insight into the redox potential of green synthesized cellulose nanocrystals in rat sub-brain sections.
- ItemPterocarpus mildbraedii (Harms) Extract Resolves Propanil-Induced Hepatic Injury via Repression of Inflammatory Stress Responses in Wistar Rats(Wiley, 2020-09-17) Otuechere, ChiagoziemPterocarpus mildbraedii (PME) is a green leafy vegetable from the Papilionaceae family. This study evaluated the anti-inflammatory activity of PME in Wistar rats exposed to experimental hepatotoxicity using propanil (PRP), a post-emergent herbicide. Animals were grouped as control, PRP, PME, and PME + PRP. After 7 days, the levels of stress-activated protein kinases/c-Jun N-terminal kinase (SAPK/JNK), p38 mitogen-activated protein kinase (p38 MAPK), and signal transducer and activator of transcription (STAT-3) were measured in rat liver. Furthermore, myeloperoxidase (MPO) and nitric oxide (NO) levels, as well as protein expressions of nuclear factor-κB (NF-κB p65), inducible nitric oxide synthase (iNOS), and cyclo-oxygenase-2 (COX-2) were determined. Compared with PRP-treated rats, PME significantly reduced the hepatic MPO and NO levels. PME also diminished NFκB, iNOS, and COX-2 protein expressions in PRP-treated rats. This study showed that Pterocarpus mildbraedii leaves produce active principles with relevant anti-inflammatory potential. Practical applications Previous studies have shown that bioactive principles contained in medicinal plants can offer protection against chemically induced inflammation. Pterocarpus mildbraedii leaves, with rich content of polyphenols, flavonoids, and essential fatty acids, could be exploited as a therapeutic agent against pesticide-induced oxidative stress and inflammation. This current study has also shown that the potential of PME as a functional food is boosted by the presence of α-linolenic acid, an omega-3-fatty acid known to possess anti-inflammatory activity. Here, we elucidated the cellular mechanisms of the anti-inflammatory action of PME.
- ItemPterocarpus mildbraedii leaf extract ebbs Propanil-induced Oxidative and Apoptotic Damage in the Liver of Rats(Taylor and Franscis, 2020-11-04) Otuechere, ChiagoziemPhytochemicals derived from plant sources are well recognized as sources of pharmacologically potent drugs in the treatment of several oxidative stress-related ailments. Dichloromethane/methanol (1:1) leaf extract of Pterocarpus mildbraedii was evaluated for its possible protection against oxidative stress and apoptosis in the liver of male Wistar rats exposed to propanil (PRP). In the experimental design, olive oil served as the vehicle, and rats were grouped into control (2 mL/kg olive oil), PRP (200mg/kg/day), Pterocarpus mildbraedii extract (200 mg/kg/day), and Pterocarpus mildbraedii extract (200mg/kg/ day)þPRP (200 mg/kg/day), and treated daily, p.o., for seven days. Oxidative stress parameters, B-cell lymphoma 2 (Bcl-2), Bcl 2-associated X protein (Bax), p53, caspases (9/3), and terminal transferase dUTP nick end labeling (TUNEL) assays were observed in all groups. Propanil significantly elevated superoxide dismutase and lipid peroxidation levels, while concomitantly depleting GSH and p53 levels. Further, PRP enhanced the expressions of caspase-9, caspase-3, Bax, and TUNEL-positive cells in the liver of rats. However, these observed alterations were reversed following treatment with Pterocarpus mildbraedii extract. Our studies suggest that Pterocarpus mildbraedii extract protected against PRP toxicity by reducing oxidative stress and attenuating critical endpoints in the intrinsic apoptotic pathway.