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Despite reports that quinoline antimalarials including chloroquine (Chq) exhibit idiosyncratic neuropsychiatric effects even at low doses, the drug continues to be in widespread use during pregnancy. Surprisingly, very few studies have examined the potential neurotoxic action of Chq exposure at different points of gestation or how this phenomenon may affect neurophysiological well-being in later life. We therefore studied behavior, and the expression of specific genes and neurochemicals modulating crucial neural processes in offspring of rats exposed to prophylactic dose of Chq during different stages of gestation. Pregnant rats were injected 5 mg/kg/day (3 times) of Chq either during early- (first week), mid- (second week), late- (third week), or throughout- (all weeks) gestation, while controls received PBS injection. Behavioral characterization of offspring between postnatal days 15-20 in the open field, Y-maze, elevated plus and elevated zero mazes revealed that Chq evoked anxiogenic responses and perturbed spatial memory in rats, although locomotor activity was generally unaltered. In the prefrontal cortex (PFC), hippocampus and cerebellum of rats prenatally exposed to Chq, RT-qPCR analysis revealed decreased mRNA expression of presynaptic marker synaptophysin, which was accompanied by downregulation of postsynaptic marker PSD95. Synaptic marker PICK1 expression was also downregulated in the hippocampus but was unperturbed in the PFC and cerebellum. In addition to recorded SOD downregulation in cortical and hippocampal lysates, induction of oxidative stress in rats prenatally exposed to Chq was corroborated by lipid peroxidation as evinced by increased MDA levels. Offspring of rats infused with Chq at mid-gestation and weekly treatment throughout gestation were particularly susceptible to neurotoxic changes, especially in the hippocampus. Interestingly, Chq did not cause histopathological changes in any of the brain areas. Taken together, our findings causally link intrauterine exposure to Chq with postnatal behavioral impairment and neurotoxic changes in rats.

Nature and size of rodent cages vary from one laboratory or country to another. Little is however known about the physiological implications of exposure to diverse cage sizes in animal-based experiments.Here, two groups of male Swiss mice (Control group - Cage stationed, and Test group - Cage migrated) were used for this study. The cage-migrated mice were exposed daily to various cage sizes used across laboratories in Nigeria while the cage-stationed mice exposed daily to different but the same cage size and shape. At the end of the 30 days exposure, top-rated paradigms were used to profile changes in physiological behaviours, and this was followed by evaluation of histological and biochemical metrics.The study showed a significant (p 0.05) decrease in blood glucose levels (at 60 and 120 min of oral glucose tolerance test) in the cage-migrated mice compared to cage-stationed mice. Strikingly, peripheral oxidative stress (plasma malondialdehyde) and pain sensitivity (formalin test, hot-and-cold plate test, and von Frey test) decreased significantly in cage-migrated mice compared to cage-stationed animals. Also, the pro-inflammation mediators (IL-6 and NF-κB) increased significantly in cage-migrated mice compared to cage-stationed mice. However, emotion-linked behaviours, neurotransmitters (serotonin, noradrenaline and GABA), brain and plasma electrolytes were not significantly difference in cage-migrated animals compared to cage-stationed mice.Taken together, these results suggest that varied size cage-to-cage exposure of experimental mice could affect targeted behavioural and biomolecular parameters of pain and inflammation, thus diminishing research reproducibility, precipitating false negative/positive results and leading to poor translational outcomes.

This study evaluates the therapeutic potential of intranasal insulin (INI) in dexamethasone-induced insulin resistance in Wistar rats. In the first phase of the study, thirteen, healthy, untreated male Wistar rats were divided into 2 groups and administered either vehicle (0.9% Normal saline, 20 µl) or insulin (2 IU) intranasally to assess intranasal delivery of insulin in brain. In the second phase of experiments, to evaluate the acute effects of intranasal insulin on peripheral blood glucose, intranasal or intraperitoneal insulin was co-administered with or without dexamethasone 10 mg/kg to 26 male Wistar rats and blood glucose monitored. To evaluate effect of intranasal insulin in peripheral metabolic disease model, insulin or vehicle was administered via intranasal or intraperitoneal (IP) route to control or dexamethasone (Dex)-treated (0.5 mg/kg, IP) female Wistar rats for seven consecutive days. Twenty-four hours after last dose, trunk blood was collected via cardiac puncture. Biochemical assay of glucose, lipid and insulin was performed on serum while enzyme activity – glucokinase and glucose-6-phosphatase (G6Pase) or lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PDH) were assayed from liver and brain homogenates respectively. Acute intranasal but not intraperitoneal insulin elevated brain insulin after 30 min. In animals administered single dose of 10 mg/kg dexamethasone, intranasal and intraperitoneal insulin lowered blood glucose within one hour. However, only the former’s effect was maintained at the 3rd and fourth hour. Dex-induced hyperglycemia was associated with increased hepatic glucose-6-phosphatase activity and decreased high-density lipoprotein (HDL), these effect were attenuated by subchronic (INI) administration. Also INI did not induce oxidative stress in the brain which suggests no brain damage during the period of study. Subchronic administration of INI was able to reduce the effect of Dex-induced hyperglycemia that is associated with increased hepatic glucose-6-phosphatase activity and decreased high-density lipoprotein (HDL) without damage to the brain. We demonstrate the potential of brain targeting with intranasal insulin in a rat model of insulin resistance and peripheral metabolic disease. Keywords: Intranasal insulin, Dexamethasone, Hepatic glucose, Hyperglycemia

Background: Exposure to environmental toxins such as organophosphates poses a great threat to the health of the public. In this work, we investigated the effects of continuous exposure to dichlorvos (DDVP) on kidney function and hematological parameters, and the possible antidote activity of Nigella sativa oil (NSO). Methods: This research was conducted in 2016, at The Animal Holding and Research Laboratory of Faculty Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. Twenty-four Wistar rats were randomly divided into four groups, six rats each. The four groups received: 1. phosphate buffer solution as controls, 2. DDVP, 3. DDVP+NSO and 4. NSO alone. After 2 wk of treatment, blood samples were collected and hematological profile (RBC, Hb), erythrocyte indices (MCV, MCH, MCHC, and Plt), renal function parameters (albumin, urea, total protein, chloride, sodium, and potassium ions) and nonspecific immune response (WBC) were measured. Results: Rat exposed to DDVP showed red blood cell count, hemoglobin, packed cell volume, albumin, and total protein levels was reduced from control, while white blood cell count and urea significantly increased as compared to controls, the change in K+ level was not significant. NSO maintained optimal levels of red blood cell count, hemoglobin, packed cell volume, albumin, white blood cell count, and urea, indicative of its protective effect against hemo-, immuno- and nephrotoxicity of DDVP. Conclusion: N. sativa (Black Caraway) oil might be a potential antidote in hematotoxicity, immunosuppression and renal dysfunction in organophosphate poisoning, especially dichlorvos. The protective effect of NSO against dichlorvos toxicity can be attributed to its antioxidant capacity.

This study was conducted to evaluate cognitive enhancing effect and ameliorative effects of black seed oil in scopolamine induced rat model of cognitive impairment. These effects were investigated on scopolamine-induced dementia model in Morris water maze test (MWM) and Y maze test. The hippocampal histoarchitectural responses to scopolamine and Nigella sativa oil were also examined. Scopolamine (1 mg/kg ip) was given to induce dementia, followed by oral administration of BSO (1 ml/kg) for 14 consecutive days. MWM and Y-maze paradigms were used to assess hippocampal and frontal dependent memory respectively, thereafter the rats were sacrificed and brains were removed for histopathologic studies. Scopolamine resulted in memory impairment, by delayed latency in the MWM, reduced percentage alternation in the Y maze that was coupled by alterations in the cortico-hippocampal neurons. Posttreatment of rats with BSO mitigated scopolamine-induced amnesia, by reducing latency period and increasing percentage alternation and histological changes. The observed anti-amnestic effect of BSO makes it a promising anti-amnesic agent for clinical trials in patients with cognitive impairment.

Aim: Nigella sativa oil has been shown to improve metabolic syndrome-associated dyslipidemia and oxidative stress. Effects of N. sativa oil on letrozole-induced polycystic ovary syndrome (PCOS)-associated hormonal, metabolic, redox, and lipid dysregulation in rats were investigated. Methods: Female Sprague-Dawley rats were randomly assigned into four groups (n=10 per group): control, PCOS, and PCOS treated with N. sativa oil (5 mL/kg/day or 10 mL/kg/day) once daily p.o. starting at day 7 after the commencement of letrozole (1mg/kg) until day 56. Body weight and estrous cycle were recorded starting from days 7 and 28 respectively until day 56. Rats were dissected and serum and ovaries were collected for biochemical and histomorphological assessments. Results: N. sativa oil (10 mL/kg/day) treatment significantly increased: number of rats undergoing regular cycle (80% vs 20%; p< 0.05), average number of regular cycles (5.00±0.59 vs 0.20±0.42; p< 0.05), appearance of corpus luteum; but reduced number of cystic follicles (7.60±1.51 vs 6.10±0.19; p< 0.05) in PCOS rats. Body weight was also reduced by the oil in PCOS rats. However, ovarian weight, granulose and theca cells layers showed no significant change. The oil also restored altered circulating levels of gonadotropins, steroids and reduced fasting blood glucose. The ovarian total cholesterol, triglycerides, low density lipoprotein-cholesterol, malondialdehyde were markedly reduced while insulin sensitivity and ovarian high density lipoprotein-cholesterol, superoxide dismutase and glutathione peroxidase activities were greatly increased. Conclusion: N. sativa oil improved polycystic ovarian-morphology and metabolic disorders via its anti-androgenic and insulin-sensitizing actions to ameliorate PCOS-associated dyslipidemia and redox disturbances.