Dry-feed Added Quercetin Mitigates Cyclophosphamide-induced Oxidative Stress, Inflammation and Gonadal Fibrosis in Adult Male Rats.

BACKGROUND: Cyclophosphamide (CYP), a widely used cancer chemotherapeutic agent has been linked with male gonadotoxicity, resulting in infertility. The notion that potent antioxidants could be beneficial in mitigating CYP-induced gonadotoxicity necessitated this research. Therefore, we examined the effects of feed-added quercetin on CYP-induced gon-adotoxicity in male rats. METHODS: Male postpubertal rats were randomly assigned into six groups of 10 rats each. The normal control (fed standard rodent diet) and two groups fed quercetin-supplemented diet at 100 and 200 mg/kg of feed received normal saline intraperitoneally at 2 ml/kg daily. A fourth group which served as the CYP control (fed standard rodent diet) and the last two groups fed quercetin at 100 and 200 mg/kg of feed were administered CYP at 150 mg/kg/day. Rats were administered normal saline or CYP intraperitoneally on days 1 and 2, while standard diet or feed-added quercetin was administered daily for 21 days. On day 22, half of the animals were either sacrificed or paired with age-matched females for fertility assessment. Estimation of testosterone levels, antioxidant, anti-inflammatory markers, and histomorphological exami-nation of the testis and epididymis was also assessed. RESULTS: The administration of CYP was associated with weight loss, decreased food intake, decreased antioxidant capacity, increased gonadosomatic index, increased lipid peroxidation, sub-fertility, and histological evidence of gonadal injury. However, administration of querce-tin reversed CYP-induced changes. CONCLUSION: The result of this study suggests that dietary quercetin supplementation has the ability to mitigate CYP induced gonadotoxicity and mitigate subfertility in male rats. How-ever, further studies are required to assess its possible use in humans.

Prepubertal Continuous Dietary Folate Fortification Enhances the Brain Function of Adult Mice by Modulating Antioxidant Status, Inflammation, and Brain Neurotransmitter Levels.

BACKGROUND: The benefits of folic acid supplementation have been documented in several studies. However, while evidence exists regarding its benefits for growth and haematologic parameters, its possible effects on the brain have been less examined. OBJECTIVES: The study aimed to examine the benefits of dietary folic acid supplementation (beginning in the prepubertal period) on neurobehaviour, oxidative stress, inflammatory parameters, and neurotransmitter levels in adult mice. METHODS: Forty-eight prepubertal male mice were assigned into four groups of 12 animals each. Mice were grouped into normal control (fed standard diet) and three groups fed folic acid supplemented diet at 2.5, 5, and 10 mg/kg of feed. Animals were fed a standard diet or folic acid-supplemented diet for eight weeks during which food intake and body weight were assessed. On postnatal day 78, animals were exposed to the open-field, Y-maze, radial arm maze, elevated plus maze, bar test, and models of behavioural despair. 24 hours after the last behavioural test, animals were made to fast overnight and then sacrificed by cervical dislocation. Blood was then taken for the assessment of blood glucose, leptin, and insulin levels. Homogenates of brain tissue were prepared and used for the assessment of biochemical parameters. RESULTS: Results showed a concentration-dependent increase in body weight, and improved antioxidant status, memory scores, and acetylcholine levels. Also, a decrease in food intake, blood glucose, insulin, and leptin levels was observed. A reduction in open-field behaviour, anxiety-related behaviour, and proinflammatory markers, was also observed. CONCLUSION: The beneficial effect of prepubertal continuous dietary folate fortification on the brain (as the animal ages) has been shown in this study.

Microbiome-Based Therapies in Parkinson's Disease: Can Tuning the Microbiota Become a Viable Therapeutic Strategy?

Progressive neurodegenerative disorders such as Parkinson's disease (PD) have continued to baffle medical science, despite strides in the understanding of their pathology. The inability of currently available therapies to halt disease progression is a testament to an incomplete understanding of pathways crucial to disease initiation, progression and management. Science has continued to link the activities and equilibrium of the gut microbiome to the health and proper functioning of brain neurons. They also continue to stir interest in the potential applications of technologies that may shift the balance of the gut microbiome towards achieving a favourable outcome in PD management. There have been suggestions that an improved understanding of the roles of the gut microbiota is likely to lead to the emergence of an era where their manipulation becomes a recognized strategy for PD management. This review examines the current state of our journey in the quest to understand how the gut microbiota can influence several aspects of PD. We highlight the relationship between the gut microbiome/microbiota and PD pathogenesis, as well as preclinical and clinical evidence evaluating the effect of postbiotics, probiotics and prebiotics in PD management. This is with a view to ascertaining if we are at the threshold of discovering the application of a usable tool in our quest for disease modifying therapies in PD.

Neuroinflammation and Oxidative Stress in Alzheimer's Disease; Can Nutraceuticals and Functional Foods Come to the Rescue?

Alzheimer's disease (AD), the most prevalent form of age-related dementia, is typified by progressive memory loss and spatial awareness with personality changes. The increasing socioeconomic burden associated with AD has made it a focus of extensive research. Ample scientific evidence supports the role of neuroinflammation and oxidative stress in AD pathophysiology, and there is increasing research into the possible role of anti-inflammatory and antioxidative agents as disease modifying therapies. While, the result of numerous preclinical studies has demonstrated the benefits of anti-inflammatory agents, these benefits however have not been replicated in clinical trials, necessitating a further search for more promising anti-inflammatory agents. Current understanding highlights the role of diet in the development of neuroinflammation and oxidative stress, as well as the importance of dietary interventions and lifestyle modifications in mitigating them. The current narrative review examines scientific literature for evidence of the roles (if any) of dietary components, nutraceuticals and functional foods in the prevention or management of AD. It also examines how diet/ dietary components could modulate oxidative stress/inflammatory mediators and pathways that are crucial to the pathogenesis and/or progression of AD.

Anti-Inflammatory, Anti-Oxidant, and Anti-Lipaemic Effects of Daily Dietary Coenzyme-Q10 Supplement in a Mouse Model of Metabolic Syndrome.

BACKGROUND: The dietary model of metabolic syndrome has continued to aid our understanding of its pathogenesis and possible management interventions. However, despite progress in research, therapy continues to be challenging for humans; hence, the search for newer treatment and prevention options continues. OBJECTIVE: The objective of this study was to evaluate the impact of dietary CQ10 supplementation on metabolic, oxidative, and inflammatory markers in a diet-induced mouse model of metabolic syndrome. METHODS: Mouse groups were fed a Standard Diet (SD), High-Fat High-Sugar (HFHS) diet, and SD or HFHS diet (with incorporated CQ10) at 60 and 120 mg/kg of feed. At the completion of the study (8 weeks), blood glucose levels, Superoxide Dismutase (SOD) activity, plasma insulin, leptin, adiponectin, TNF-α, IL-10, serum lipid profile, and Lipid Peroxidation (LPO) levels were assessed. The liver was either homogenised for the assessment of antioxidant status or processed for general histology. RESULTS: Dietary CQ10 mitigated HFHS diet-induced weight gain, decreased glucose, insulin, and leptin levels, and increased adiponectin levels in mice. Coenzyme-Q10 improved the antioxidant status of the liver and blood in HFHS diet-fed mice while also decreasing lipid peroxidation. Lipid profile improved, level of TNF-α decreased, and IL-10 increased following CQ10 diet. A mitigation of HFHS diet-induced alteration in liver morphology was also observed with CQ10. CONCLUSION: Dietary CQ10 supplementation mitigates HFHS diet-induced changes in mice, possibly through its anti-oxidant, anti-lipaemic, and anti-inflammatory potential.

Concentration-dependent Effects of Dietary L-Ascorbic Acid Fortification in the Brains of Healthy Mice.

BACKGROUND: Ascorbic acid (AA) is a water-soluble vitamin that is concentrated in the brain in large quantities. There have been reports that it is essential for proper brain functioning. However, there is insufficient information on the possible effects of dietary fortification with AA on the health of the brain. OBJECTIVE: This study examined the effects of dietary fortification of rodent chow with AA on neurobehaviour, antioxidant status, lipid peroxidation, and inflammatory/apoptotic markers in the brain of healthy mice. METHODS: Mice were randomly assigned into four groups of ten animals each. Groups were normal control [fed rodent chow], and three groups were fed AA-fortified chow at 100, 200, and 300 mg/kg of feed, respectively, for eight weeks. Behavioural tests {Open field, Y-maze, radial-arm maze, and elevated plus maze (EPM)} were carried out on day 57. Twenty-four hours after the last behavioural test, animals were euthanised, and the brains were excised and homogenised for assessment of brain acetylcholinesterase activity, lipid peroxidation, antioxidant status, inflammatory and apoptotic markers. RESULTS: Ascorbic acid fortified diet was associated with concentration-dependent changes in body weight, open-field behaviours, working-memory, and anxiety indices. Also, brain levels of malondialdehyde, caspase-3, and TNF-α decreased, while superoxide dismutase activity, total antioxidant capacity, and IL-10 level increased. CONCLUSION: Dietary AA fortification with concentrations up to 300 mg/kg of feed was associated with sustained improvement in neurobehavioural and biochemical parameters in the brain of healthy mice, reiterating additional health benefits of AA fortification beyond the prevention of nutritional deficiencies.

Lepidium meyenii Supplemented Diet Modulates Neurobehavioral and Biochemical Parameters in Mice Fed High-Fat High-Sugar Diet.

BACKGROUND: Metabolic syndrome has been associated with an increased risk of cardiovascular disease, diabetes mellitus, and neurodegenerative disorders. Known side-effects of currently- available drugs necessitate the search for possibly better treatment options. OBJECTIVE: This study examined the effects of dietary lepidium meyenii (MACA) supplementation on neurobehaviour, metabolic profile, levels of inflammatory markers, and oxidative stress parameters in a mouse model of metabolic syndrome. METHODS: Mice were randomly assigned into 8 groups of ten animals each. Groups consist of standard diet (SD) control, high fat/high sugar (HFHS) control and three groups each of lepidium meyenii incorporated into either SD or HFHS diet at 0.1, 0.2 and 0.4%. Mice were fed for seven weeks, and body weight was measured weekly. Open-field behaviors and radial-arm/Y-maze spatial memory were scored at the end of the study. Twenty-four hours after the last behavioral test, fasting blood glucose levels were estimated. Animals were then euthanized, and blood was drawn for estimation of serum lipid profile. Whole brains were excised, weighed and homogenized to estimate the levels of lipid peroxidation, inflammatory markers, antioxidant status, and acetylcholinesterase activity. RESULTS: MACA-supplemented diet was associated with a decrease in body weight gain, an increase in food intake (at lower concentrations), suppression of grooming behavior, and decrease in acetylcholinesterase activity. MACA-supplement also reversed HFHS-induced memory impairment, anxiety, hyperglycaemia, lipid derangement, oxidative stress, and derangement of inflammatory markers. CONCLUSION: Dietary supplementation with MACA shows beneficial effects in mitigating the effects of metabolic syndrome on the brain in mice.

Food-added azodicarbonamide alters haematogical parameters, antioxidant status and biochemical/histomorphological indices of liver and kidney injury in rats.

OBJECTIVES: Azodicarbonamide (ADA) is a dough enhancer currently used as a replacement for potassium bromate in the process of bread-making in countries such as Nigeria. However, comprehensive information on the toxicological profile of ADA is not readily available. The present study investigated the toxicological effects of ADA in rats. METHODS: Twenty-four adult rats were randomly assigned into four groups of six rats each. Animals in group A served as the control (administered standard diet), whereas animals in groups B, C and D were fed ADA in food at 1, 2 and 4%, respectively. Standard or ADA diet was fed to the animals daily for a period of 28 days. Body weight was measured weekly, whereas food and water consumption was measured daily. On day 28, animals were fasted overnight after which they were euthanised. Blood samples taken were used for assessment of fasting blood glucose, haematological parameters, serum lipids, antioxidant status, lipid peroxidation status, electrolytes and urea, plasma proteins and biochemical parameters of liver and kidney injury. The liver and kidneys were then excised and processed for general histological study. RESULTS: The results showed that repeated administration of ADA was associated with dose-related decrease in weight gain, decrease in overall food consumption, decreased superoxide dismutase activity/glutathione level and increased lipid peroxidation. There was also biochemical and morphological evidence of liver and kidney injury. CONCLUSIONS: These findings suggest that food-added ADA could be injurious to the body cells and organs in rats.

An Evaluation of the Effects of Pyridoxal Phosphate in Chlorpromazineinduced Parkinsonism using Mice.

BACKGROUND: Parkinsonism is a neurodegenerative disorder with a heavy disease burden, despite the discovery and application of drugs. Current research is beginning to suggest the possible crucial roles of micronutrients such as pyridoxal phosphate in the prevention or management of neurodegenerative disorders. OBJECTIVE: We investigated the possible protective effects of supplemental pyridoxal phosphate in Chlorpromazine (CPZ)-induced Parkinsonism-like changes in mice. METHODS: Mice were assigned to eight groups of 30 mice each. Groups included Vehicle control (fed standard diet (SD), and administered intraperitoneal {ip} injection of saline and saline per orem), levodopa-carbidopa (LD) group (SD, saline ip and LD per orem), two groups fed pyridoxal phosphate-supplemented diet (at 100 and 200 mg/kg of feed), and administered saline both ip and orally, CPZ group (SD, CPZ ip and saline per orem), CPZ/LD group (SD, CPZ ip and LD per orem) and finally two groups fed pyridoxal phosphate -supplemented diet (at 100 and 200 mg/kg of feed) and administered CPZ ip plus saline per orem. Treatments were administered daily for a period of 21 days to allow for the induction of Parkinsonism features. Body weight and food intake were measured weekly while neurobehavioural and biochemical tests were assessed at the end of the experimental period. RESULTS: Pyridoxal phosphate supplementation was associated with a reduction in CPZ-induced suppression of open-field horizontal locomotion and rearing; and a significant increase in grooming activity. Administration of pyridoxal phosphate-supplemented diet was also associated with improvements in working-memory in CPZ-treated mice; and there was reduction in the index of anxiety and catalepsy score. CONCLUSION: Pyridoxal phosphate supplementation was associated with significant benefits in CPZ-induced Parkinsonism-like changes in mice.

High Dietary Fat Modulates Neurobehavioural Effect of Lopinavir/ Ritonavir in Mice.

BACKGROUND: Lopinavir/Ritonavir (LR) is a protease inhibitor used human immunodeficiency virus infection management. There have been issues regarding the effects of fat on LR efficacy and the possibility of neurological deficits following prolonged use, there is however a dearth of research examining this. AIMS: The effects of LR administered with normal or High-Fat Diet (HFD) on neurobehaviour, neurochemistry and oxidative stress in healthy mice were examined. METHODS: Mice were randomly-assigned into eight groups of ten (n=10) animals each. The groups were normal control [Standard Diet, (SD)], HFD control, 3 groups of LR incorporated into SD (100/25, 200/50 and 400/100 mg/kg of feed), and 3 groups of LR with HFD (100/25, 200/50 and 400/100 mg/kg of feed). Mice were fed daily for six weeks, following which open field, elevated-plus maze (EPM), radial-arm maze and Y-maze behaviours were scored. Twenty-four hours after tests, mice were euthanised and brains were homogenised for estimation of oxidative stress, L-glutamate level and acetylcholinesterase activity. RESULTS: LR was associated with a reduction in HFD-induced weight gain, suppression of open-field behaviours with SD, and counteraction of HFD-induced changes in working-memory, open-field and anxiety-related behaviours. Also, LR causes increased lipid peroxidation and superoxide dismutase activity; and a decrease in brain glutamate, irrespective of dietary composition. Increased fat catabolism leading to increased oxidative stress could possibly account for the weight changes, while a decrease in brain glutamate could account for the changes in open-field behaviours in mice fed SD. CONCLUSION: LR alters neurobehaviour, oxidative stress and brain glutamate in mice; however, only its effects on neurobehaviour are affected by diet.

An Assessment of the Effects of Azodicarbonamide-containing Diet on Neurobehaviour, Brain Antioxidant Status and Membrane Lipid Peroxidation Status in Rats.

BACKGROUND: Azodicarbonamide is a dough-enhancer used in the process of breadmaking in countries like Nigeria. While there have been suggestions that it is a sensitizer of the respiratory system, there is a dearth of information on its effects on the central nervous system. AIM: This study assessed the effects of azodicarbonamide on the central nervous system (ADA) in rats. OBJECTIVE: The effects of ADA-containing diet on neurobehaviour, brain antioxidant status, and neuromorphology of selected brain regions in rats were examined. METHODS: Forty adult rats were randomly-assigned into four groups of ten rats each, and were given standard diet or diet containing ADA at 1, 2 and 4% respectively. Rats were fed a standard diet or ADA-containing diet for a period of 28 days. Weekly body weight assessment and daily estimation of food intake were done. Behavioural tests {in the Open field, Y-maze, radial-arm maze, and Elevated Plus Maze (EPM)} were conducted on day 29. Twenty-four hours after the last behavioural test, animals were euthanised, whole brains were dissected, weighed, and either homogenised for assessment of lipid peroxidation and antioxidant status; or sectioned and processed for general histology. RESULTS: Consumption of ADA-containing diet was associated with a significant decrease in weight gain/food intake, and significant suppression of horizontal locomotion and rearing behaviours; however, grooming activity increased significantly. Also, there was a significant reduction of open-arm time in the EPM and a significant increase in Y-maze alternation (at the lowest concentration of ADA). ADA-containing diet was not associated with significant changes in brain oxidative status or neuromorphology. CONCLUSION: The study showed that while ADA-containing diet may alter neurobehaviour in rats; this was not associated with evidence of brain oxidative stress or neuro-histomorphological alterations.