Biology subjects

Onaolapo, A. Y.

Publications and source records attributed to Onaolapo, A. Y..

9 recordsLinked to original sources

bioRxiv2026

Nutritional Protection Against Antipsychotic-Related Brain Injury: Combined Omega-3 and Vitamin E Effects on the Cerebellum

Haloperidol is a widely used typical antipsychotic for schizophrenia but is associated with neurotoxic effects mediated by oxidative stress, neuroinflammation, and neuronal disruption. Omega-3 fatty acids possess anti-inflammatory and neuroprotective properties, while vitamin E is a potent lipid-soluble antioxidant. Although each has shown protective effects individually, their combined efficacy against haloperidol-induced cerebellar toxicity remains poorly understood. This study investigated the neuroprotective effects of co-administered omega-3 fatty acids and vitamin E on haloperidol-induced behavioural, biochemical, and histological alterations in the rat cerebellum. Sixty male Wistar rats (80-100 g) were randomly assigned to six groups (n = 10). Control animals received a standard diet and olive oil, while treatment groups received omega-3 fatty acids (500 mg/kg of feed), vitamin E (10 IU/kg, orally), haloperidol (1 mg/kg, intraperitoneally), or their combinations for 28 days. Haloperidol-treated rats showed significant reductions in body weight, feed intake, locomotor activity, rearing, and spatial working memory, alongside increased grooming behaviour and catalepsy (p < 0.05). These behavioural deficits were markedly attenuated by omega-3 fatty acids and vitamin E, particularly when administered together. Haloperidol also increased malondialdehyde and pro-inflammatory cytokines (IL-1{beta}, IL-6, TNF-) while reducing total antioxidant capacity, indicating heightened oxidative stress and inflammation. Co-treatment with omega-3 fatty acids and vitamin E significantly reversed these biochemical alterations. Histological analysis revealed pronounced cerebellar neuronal degeneration in haloperidol-only rats, whereas cerebellar architecture was largely preserved in co-treated groups. Overall, combined omega-3 fatty acid and vitamin E supplementation provided significant neuroprotection against haloperidol-induced cerebellar toxicity and motor impairment, supporting their potential role as adjunct therapies in reducing antipsychotic-related neurodegeneration.

neuroscience↗

bioRxiv2025

Possible Synergistic Modulation of Hormonal Balance and Ovarian Structure by Clomiphene Letrozole Co-Administration in a Rodent Model of Hyperandrogenism

Infertility, defined as the inability to achieve pregnancy after 12 months of unprotected intercourse, is a major reproductive health concern. In females, hyperandrogenism often contributes to polycystic ovarian syndrome (PCOS), a leading cause of infertility. Although clomiphene and letrozole are widely used as ovulation inducers, their individual efficacy is limited, and the potential benefit of combined therapy remains unclear. This study investigated the effects of clomiphene-letrozole co-administration on gonadotrophic hormones, inflammatory cytokines, antioxidant status, and ovarian histomorphology in a rat model of hyperandrogenism. Thirty female Wistar rats were randomised into five groups (n=6). Group A received saline, while groups B-E were administered testosterone enanthate (10 mg/kg, subcutaneous injection) for 35 days to induce PCOS. Group B served as PCOS control, while groups C, D, and E were additionally treated with clomiphene (100 {micro}g/kg), letrozole (5 mg/kg), or their combination, respectively, for 10 days from day 36. Hormonal assays, cytokine profiling, antioxidant measurements, and ovarian histology were performed. Results showed that the co-administration significantly reduced body and ovary weights, lowered glucose levels, and improved oestradiol and follicle-stimulating hormone profiles compared with PCOS controls. Combination therapy also enhanced antioxidant capacity, reduced lipid peroxidation, and modulated inflammatory cytokines by lowering IL-1{beta} and TNF- while elevating IL-10. Histological evaluation revealed cystic follicles with basement membrane thickening in the PCOS control, consistent with ovarian hyperstimulation; and a reversal with clomiphene and or letrozole treatment. In conclusion, clomiphene-letrozole co-administration demonstrated superior benefits over monotherapy in modulating endocrine, oxidative, and inflammatory parameters, suggesting a potential therapeutic advantage in ovulation induction for PCOS-related infertility.

pharmacology and toxicology↗

bioRxiv2025

Assessment of the Effects of Muira Puama Root Extract on Biochemical Indices, and Testicular Histomorphology in Cyclophosphamide-treated Rats

Cyclophosphamide (CYP), a commonly used anticancer drug, is limited in its therapeutic application by gonadotoxic effects driven by oxidative stress and inflammation. This study investigated the protective role of Muira puama (MP) extract against CYP-induced testicular damage in rats. Sixty rats were randomly assigned into six groups: Group A (control) received normal saline; Groups B and C were treated with MP (25 mg/kg and 50 mg/kg feed, respectively); Group D received CYP alone; and Groups E and F were co-administered CYP with MP (25 mg/kg and 50 mg/kg, respectively). Treatments lasted four weeks, after which body weight, feed intake, serum interleukin-10 (IL-10), Tumour necrosis factor-alpha (TNF-), malondialdehyde (MDA), total antioxidant capacity (TAC), hormonal levels and testicular histology were evaluated. CYP administration (Group D) significantly reduced weight gain, feed intake, Testosterone and IL-10 levels, while elevating MDA and TAC (p < 0.05). Co-treatment with MP (Groups E and F) improved body weight, feed intake, and IL-10 levels, while reducing MDA and mitigating testicular histopathological damage. The higher MP dose (50 mg/kg) conferred greater protection. TAC values in MP co-treated groups were lower than with CYP alone, suggesting modulation of antioxidant responses. Histological analysis showed severe seminiferous tubule degeneration and basement membrane disruption in CYP-treated rats, whereas MP preserved testicular architecture, particularly at 50 mg/kg. In conclusion, Muira puama extract attenuates CYP-induced gonadotoxicity through antioxidant and anti-inflammatory mechanisms, supporting its potential as a protective agent against chemotherapy-related reproductive toxicity.

pharmacology and toxicology↗

bioRxiv2025

Human-dose equivalent 5-fluorouracil induces graded neurobehavioural, neuromorphological and immunohistochemical changes in the cerebral cortex of Wistar rats

5-Fluorouracil (5-FU) is an antimetabolite widely used in cancer chemotherapy. Despite its central role in many anticancer regimens information on its potential effects on the central nervous system (CNS) remains limited. This study investigated the effects of human dose equivalent 5-FU on the cerebral cortex of rats. Fifty male rats were randomly assigned into five groups (n=10). The control group received intraperitoneal (i.p.) saline, while four experimental groups received i.p. 5-FU at 12.5 25 50 or 100 mg/kg body weight. Saline or 5-FU was administered for four consecutive days, followed by alternate-day dosing until day 12. Behavioral assessments were conducted and animals were sacrificed 24 hours after the final test. Cortical tissues were analyzed using biochemical assays histology and immunohistochemistry. 5-FU administration caused dose-dependent decreases in body weight food intake and locomotor activity. Treated rats also showed impaired spatial working memory and reduced time spent in the open arms of the elevated plus maze. Biochemically 5-FU significantly increased cortical malondialdehyde and tumor necrosis factor-alpha levels while total antioxidant capacity and interleukin-10 levels decreased. Histological analysis revealed progressive disruption of cortical cytoarchitecture with increasing doses. 5-FU induces dose-dependent neurotoxicity in the rat cerebral cortex characterized by behavioral deficits, oxidative stress neuroinflammation and histomorphological alterations. These findings highlight the need to better understand and mitigate CNS toxicity associated with 5-FU-based chemotherapy.

neuroscience↗

bioRxiv2025

Cholecalciferol Ameliorates Cyclophosphamide-induced Behavioural Toxicities in Wistar Rats

Cholecalciferol (Vitamin D3) is a dietary supplement that has been shown to play crucial roles in brain development, immune regulation, neurotransmission and neuroprotection. While there are reports that it influences cognition and mental health there is a dearth of information on its benefits in mitigating cyclophosphamide induced behavioural deficits. This study investigated the possible protective effects of cholecalciferol supplementation on cyclophosphamide induced alterations in open field behaviours, spatial working memory and anxiety-related behaviours in rats. Sixty rats were randomly assigned into six groups (n=10). Groups A and D served as normal and cyclophosphamide control respectively and were fed standard rat chow, groups B and E received Vitamin D3 (300 IU/kg), while groups C and F received Vitamin D3 (600 IU/kg). Animals in group A-C received intraperitoneal normal saline on day1, while groups D-F got intraperitoneal Cyclophosphamide (100 mg/kg/day on day1). Standard diet and Vitamin D3 supplementation were administered daily for 15 days. At the end of the experimental period, animals were exposed to the behavioural paradigm (open field, Y-maze, and elevated plus maze). Vitamin D3 mitigated CYP-induced anxiogenic behaviour (dose-dependent). It also significantly improved spatial working memory. The results highlight Vitamin D3s ability to influence CYP-induced loss in cognition in rats via its anxiolytic, cognitive and immune modulatory properties. They also harness Vitamin D3s potential as a possible adjunct in cancer chemotherapy. However, further research will be needed to specify its exact role in cancer chemotherapy.

pharmacology and toxicology↗

bioRxiv2025

Quercetin Mitigates Aluminium Chloride-Induced Neurotoxicity by Modulating Oxidative Stress, Neuroinflammation, and Neurotransmitter Dysregulation in Rats

Memory impairment, characterized by reduced ability to recall facts, information, and experiences, is increasingly recognized as a major public health concern. This trend is largely driven by the rising prevalence of age-related cognitive decline and Alzheimers disease within the aging population. Aluminium chloride (AlCl{square}), a well-established neurotoxicant, induces neurobehavioral and biochemical alterations that mimic key features of neurodegenerative disorders, thus serving as a reliable experimental model for evaluating neuroprotective agents. This study assessed the neuroprotective efficacy of quercetin in a rat model of AlCl{square}-induced neurotoxicity. Fifty adult male rats (n = 10 per group) were randomly assigned into five groups. Neurotoxicity was induced by oral administration of AlCl{square} (100 mg/kg/day) for 14 days. Subsequently, from days 14 to 35, rats received daily treatments of quercetin (100 or 200 mg/kg), donepezil (3 mg/kg), or vehicle control. AlCl{square} exposure significantly impaired body weight gain, feed intake, locomotor activity, grooming behaviour, and spatial memory performance. Quercetin treatment markedly ameliorated these deficits, as evidenced by improved performance in Y-maze and radial-arm maze tasks. Biochemical analysis revealed that quercetin significantly reduced lipid peroxidation, enhanced total antioxidant capacity, and modulated inflammatory responses by decreasing pro-inflammatory cytokines (IL-1{beta}, TNF-) and elevating anti-inflammatory IL-10 levels. Furthermore, quercetin restored acetylcholine and brain-derived neurotrophic factor (BDNF) concentrations and preserved hippocampal cytoarchitecture, as demonstrated by histopathological assessment. These findings highlight quercetins therapeutic potential in mitigating aluminium-induced neurotoxicity and suggest its utility in the management of neurodegenerative disorders.

animal behavior and cognition↗

bioRxiv2023

Induced-hyperandrogenism in female rats: assessing possible modulation of neurobehavioural and neurotransmitter changes following clomiphene/letrozole intervention

Hyperandrogenism is the excessive production of androgenic hormones resulting in infertility in a number of women. While letrozole and clomiphene citrate have been used to increase chances of achieving pregnancy, their effects on the brain has been scarcely studied. This study examined the effects of clomiphene and letrozole alone or in combination on neurobehavioural and neurochemical changes in female rats exposed to testosterone. Weaned rats were assigned into eight groups of ten each. Animals were grouped as normal control administered vehicle (normal saline) orally at 10 ml/kg or subcutaneously at 2 ml/kg, three groups administered clomiphene (CLOM) at 100 {micro}g/kg, letrozole (LETR) at 5 mg/kg and or a combination of clomiphene and letrozole (CLOM/LETR) orally and saline subcutaneously. There were also four groups Testosterone (Test), Test/CLOM, Test/LETR or Test/CLOM+LETR administered testosterone enantate subcutaneously at 1 mg/100 g. Testosterone or saline was administered from day 1-35, while beginning on day 36, clomiphene, letrozole or saline was administered daily for 10 days. At the end of the dosing period, animals were exposed to different behavioural paradigms. After the behavioural tests, animals were sacrificed, the cerebral cortex was homogenised for the assessment of biochemical assays. The result showed an increase in body weight, food intake, locomotor activity, rearing and self grooming with CLOM, LETR and CLOM/LETR in all treated groups. Decreased spatial working memory and anxiolysis was observed with letrozole and/or clomiphene. Increased oxidative stress, decreased total antioxidant capacity, altered inflammatory cytokines and brain neurotransmitter were observed with letrozole and /or clomiphene. In conclusion, the administration of clomiphene and/or letrozole was associated with significant alterations in brain function, oxidative stress, inflammatory markers and brain neurotransmitter levels.

neuroscience↗

bioRxiv2023

Dietary zinc protects against methotrexate-induced neurotoxicity in rats via modulation of oxidative stress, inflammation and neuronal energy metabolism

BackgroundIncreasing incidence of cancers and cancer chemotherapy-induced neurotoxicities makes it imperative to research compounds with neuroprotective potential that can do not impede therapy. ObjectiveTo examine the effect of dietary zinc supplementation on methotrexate-induced changes in neurobehaviour and neurochemistry and hippocampal morphology in rats. MethodsAdult male rats were assigned into five groups of twelve animals each. Group were normal control and methotrexate control fed standard rodent chow and three groups of rats fed zinc supplemented diet at 25, 50 and 100 mg/kg of feed respectively. Standard and zinc supplemented diet were administered daily for 21 days. Animals in the normal control were administered intraperitoneal injection (i.p) of normal saline at 2ml/kg, while those in the methotrexate and zinc groups were administered i.p methotrexate at 20 mg/kg/day on days 19-21. On day 22, animals were exposed to behavioural paradigm (open field, Y-maze, radial arm maze, elevated plus maze and behavioural despair test). After the last behavioural test, animals were sacrificed and blood taken for the assessment of Tumour necrosis factor-, interleukin 1{beta} and interleukin 10), malondialdehyde levels and total antioxidant capacity. The hippocampus was either homogenised for the assessment of dopamine, serotonin, acetylcholine and brain derived neurotropic factor levels or processed for histological study. ResultsDietary zinc protected against methotrexate-induced changes in weight, food intake, cognition, hippocampal histomorphology and neuron specific enolase immunohistochemistry. ConclusionDietary zinc supplementation protects against methotrexate induced neurotoxicities by modulating oxidative stress, inflammatory markers brain neurotransmitters and metabolism in rats.

neuroscience↗

bioRxiv2023

Biflavonoid quercetin protects against cyclophosphamide induced organ toxicities via modulation of inflammatory cytokines, brain neurotransmitters, and astrocyte immunoreactivity

BackgroundQuercetins antioxidative properties make it of potential benefit in many clinical conditions where oxidative stress is implicated in the pathological processes. ObjectivesTo investigate the possible protective effects of quercetin on neurobehaviour, brain oxidative status, markers of inflammation, neurotransmitter balance and astrocyte immunoreactivity in healthy rats administered cyclophosphamide. MethodsSixty rats were randomly assigned into six groups (n=10). Groups A and D served as normal and cyclophosphamide control respectively and were fed standard rat chow, groups B and E were fed quercetin supplemented diet (100 mg/kg of feed), while those in groups C and F were fed quercetin supplemented diet at 200 mg/kg of feed. Animals in group A-C also received intraperitoneal normal saline on days 1 and 2, while those in groups D-F got intraperitoneal cyclophosphamide (150 mg/kg/day on days 1 and 2). Standard diet and quercetin supplemented diet were administered daily for 21 days. At the end of the experimental period, behavioural tests were carried out, following which animals were sacrificed and blood taken for the assessment of biochemical parameters. Organs were either homogenised or processed for histological study. ResultsQuercetin mitigated CYP-induced weight loss and reduction in food consumption. It also improved total antioxidant capacity while reducing CYP-induced lipid peroxidation and biochemical markers of impaired liver function. A reduction in CYP-induced increase in urea and creatinine was also observed. Interleukin-10 increased, while the CYP-induced increase in interleukin-1 beta and TNF- were also mitigated following quercetin administration. Open field exploratory activities and grooming increased with CYP and the lowest dose of quercetin. The anxiolytic effects of quercetin was demonstrable in the elevated plus maze; while its memory-enhancing effects were seen in the Y-maze and radial-arm maze. Finally, quercetin improved acetylcholine/dopamine levels and brain-derived neurotropic factor, while reducing serotonin levels and astrocyte immunoreactivity. ConclusionThe results show quercetins ability to protect against CYP-induced changes in rats. They also highlight the possible use of quercetin as a possible adjunct in cancer chemotherapy-induced tissue damage. However, further research will be needed to delineate its exact role in cancer chemotherapy.

pharmacology and toxicology↗