Publications by authors named "R E Akhigbe"

38 Publications

Apoptotic inducement of neuronal cells by codeine: possible role of disrupted redox state and caspase 3 signaling.

Heliyon 2021 Jul 3;7(7):e07481. Epub 2021 Jul 3.

Reproductive Physiology and Bioinformatics Research Unit, Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.

Background: Codeine, a common drug of abuse, has been reported to induce organ damage; however, there are scanty available data on the effects of codeine on the brain.

Objective: Thus, we tested the hypothesis that redox dysregulation and inflammation of the brain induced by codeine exposure is 8-OHdG and/or caspase 3-dependent.

Methods: New Zealand White rabbits () received vehicle (control; n = 7), low-dose codeine (4 mg/kg/day ; n = 6), or high-dose codeine (10 mg/kg/day ; n = 6) for six weeks. Body weight was checked before and after the study.

Results: Findings showed that codeine exposure resulted in redox dysregulation (evident by elevated MDA and HO accompanied by reduced enzymatic antioxidant activities), elevated MPO activity, and distorted cytoarchitecture of the brain tissue. The observed codeine-induced redox imbalance and brain inflammation was accompanied by depletion of neuronal and purkinje cells, reduced AchE activity, and elevated 8-OHdG levels and caspase 3 activity.

Conclusions: The current study demonstrates that chronic codeine use induces oxido-inflammatory response and apoptosis of the brain tissue that is associated with neuronal and purkinje cells injury, and impaired AchE activity through 8-OHdG and/or caspase 3-dependent pathway.
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http://dx.doi.org/10.1016/j.heliyon.2021.e07481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278432PMC
July 2021

Co-administration of HAART and antikoch triggers cardiometabolic dysfunction through an oxidative stress-mediated pathway.

Lipids Health Dis 2021 Jul 5;20(1):62. Epub 2021 Jul 5.

Reproductive Biology and Toxicology Research Laboratories, Oasis of Grace Hospital, Osogbo, Osun State, Nigeria.

Background: Antikoch and highly active anti-retroviral therapy are effective drugs in the management of tuberculosis and Human Immunodeficiency Virus, respectively. However, these cocktails have been independently associated with the aetiopathogenesis of metabolic syndrome. This study investigated whether or not the co-administration of antikoch and anti-retroviral, as seen in tuberculosis/Human Immunodeficiency Virus co-infection, will produce a similar effect. Also, it evaluated the role of glutathione and adenine deaminase/xanthine oxidase/uric acid signaling in antikoch/anti-retroviral-induced cardiometabolic dysfunction.

Methods: Male rats of Wistar strain were randomized into four groups: the control, which had 0.5 mL of distilled water as a vehicle, anti-Koch-treated rats that were administered a cocktail of anti-Koch, HAART-treated rats that had a combination of anti-retroviral drugs, and anti-Koch + HAART-treated rats that had treatments as anti-Koch-treated and HAART-treated rats. The treatment was once daily and lasted for eight weeks. One way-analysis of variance followed by Tukey's posthoc test was used to test for significance and pairwise comparisons respectively.

Results: Although no changes in body weight gain and cardiac weight were noted, it was found that antikoch and/or HAART caused insulin resistance and elevated blood glucose level. In addition, antikoch and/or HAART led to dyslipidaemia, increased atherogenic indices, and elevated cardiac injury markers. These were accompanied by increased plasma and cardiac concentrations of malondialdehyde and nitric oxide, C-reactive protein, and myeloperoxidase activity, as well as suppressed activities of glutathione peroxidase and glutathione-S-transferase, and a fall in reduced glutathione level. The observed alterations were more pronounced in animals that received a combination of antikoch and HAART.

Conclusions: This study provides the first evidence that antikoch and/or HAART induce cardiometabolic dysfunction via glutathione suppression and up-regulation of adenine deaminase/xanthine oxidase/uric acid-dependent oxidative stress and inflammatory response. These events were associated with dyslipidaemia and increased atherogenic indices. This infers that regular monitoring of glucose level, insulin sensitivity, lipid profile, and oxido-inflammatory markers is important in patients on antikoch and/or HAART for prompt diagnosis and management of cardiometabolic disorder if it ensues.
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http://dx.doi.org/10.1186/s12944-021-01493-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259328PMC
July 2021

HAART exacerbates testicular damage and impaired spermatogenesis in anti-Koch-treated rats via dysregulation of lactate transport and glutathione content.

Reprod Toxicol 2021 08 9;103:96-107. Epub 2021 Jun 9.

Reproductive Biology and Toxicology Research Laboratories, Oasis of Grace Hospital, Osogbo, Osun State, Nigeria; Department of Morbid Anatomy, Obafemi Awolowo University Teaching Hospital Complex (OAUTHC), Ile-Ife, Osun State, Nigeria.

Highly active anti-retroviral therapy (HAART) is an effective anti-retroviral cocktail. Similarly, anti-Koch is highly potent against Mycobacterium tuberculosis. However, these drugs have been shown to impair male fertility. This study investigated the impact of HAART and anti-Koch, when used alone and co-administered, on testicular and sperm integrity. Thirty-two adult male Wistar rats were assigned randomly into four groups (n = 8), namely normal control, HAART-treated, anti-Koch-treated, and HAART + anti-Koch-treated. The doses of drugs were the human equivalent doses for rats. Administration was once daily per os and lasted for eight weeks. HAART aggravated anti-Koch-induced reduction in testicular and penile weights. In addition, anti-Koch also led to a distortion of testicular cytoarchitecture, disturbed spermatogenesis, and caused low sperm quality, including sperm dysmotility. More so, anti-Koch led to a significant elevation of uric acid and dysregulation of testicular lactate transport and glutathione content. These events were accompanied by enhanced lipid peroxidation and inflammation of the testicular tissue and reduced testicular and sperm DNA integrity. These adverse effects of anti-Koch were aggravated by co-administration of HAART. Thus, our results infer that HAART exacerbates anti-Koch-induced impairment of spermatogenesis and testicular and sperm toxicity through up-regulation of uric acid generation and dysregulation of lactate transport and glutathione system.
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http://dx.doi.org/10.1016/j.reprotox.2021.06.007DOI Listing
August 2021

Suppression of uric acid generation and blockade of glutathione dysregulation by L-arginine ameliorates dichlorvos-induced oxidative hepatorenal damage in rats.

Biomed Pharmacother 2021 Jun 2;138:111443. Epub 2021 Mar 2.

Department of Physiology, College of Medicine, Ladoke Akintola University of Technology, Ogbomoso, Oyo, Nigeria.

Dichlorvos is a known risk factor for organ toxicity. The liver and kidney are essential metabolic tissues but it is unclear whether or not there is associated redox dyshomeostasis in both organs in physiological and pathological states. Uric acid accumulation and glutathione dysregulation have been implicated in the aetiopathogenesis of organ damage. The antioxidant potentials of L-arginine have been shown in various conditions. The present study was thus designed to investigate the synchrony in hepatic and renal uric acid and glutathione status in dichlorvos-induced hepatorenal damage and to probe the possible therapeutic role of L-arginine. Twenty-one male Wistar rats were treated with standard rat diet and water, dichlorvos, or dichlorvos and L-arginine. Our findings revealed that dichlorvos significantly impaired hepatic and renal functions, increased hepatic and renal malondialdehyde, but reduced glutathione and activities of superoxide dismutase, catalase, and glutathione peroxidase. These events were accompanied by increased accumulation of plasma, hepatic, and renal uric acid as well as reduced body weight gain, and hepatic and renal weights. Histopathological examinations revealed hepatic and renal architectural derangement and cellular necrosis and degeneration in dichlorvos-exposed rats. Interestingly, L-arginine reversed dichlorvos-induced systemic, hepatic and renal synchronous redox dyshomeostasis. L-arginine administration also improved hepatic and renal cytoarchitecture. It is thus concluded that dichlorvos triggered synchronous uric acid generation and glutathione alterations in the liver and kidney. L-arginine confers protection against dichlorvos-induced hepatorenal damage via suppression of uric acid generation and blockade of glutathione dysregulation.
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http://dx.doi.org/10.1016/j.biopha.2021.111443DOI Listing
June 2021

The impact of reactive oxygen species in the development of cardiometabolic disorders: a review.

Lipids Health Dis 2021 Feb 27;20(1):23. Epub 2021 Feb 27.

Department of Physiology, College of Medicine, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.

Oxidative stress, an alteration in the balance between reactive oxygen species (ROS) generation and antioxidant buffering capacity, has been implicated in the pathogenesis of cardiometabolic disorders (CMD). At physiological levels, ROS functions as signalling mediators, regulates various physiological functions such as the growth, proliferation, and migration endothelial cells (EC) and smooth muscle cells (SMC); formation and development of new blood vessels; EC and SMC regulated death; vascular tone; host defence; and genomic stability. However, at excessive levels, it causes a deviation in the redox state, mediates the development of CMD. Multiple mechanisms account for the rise in the production of free radicals in the heart. These include mitochondrial dysfunction and uncoupling, increased fatty acid oxidation, exaggerated activity of nicotinamide adenine dinucleotide phosphate oxidase (NOX), reduced antioxidant capacity, and cardiac metabolic memory. The purpose of this study is to discuss the link between oxidative stress and the aetiopathogenesis of CMD and highlight associated mechanisms. Oxidative stress plays a vital role in the development of obesity and dyslipidaemia, insulin resistance and diabetes, hypertension via various mechanisms associated with ROS-led inflammatory response and endothelial dysfunction.
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http://dx.doi.org/10.1186/s12944-021-01435-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916299PMC
February 2021
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