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Adeola Olubunmi Ajibare,1 Olatunde Peter Olabode,2 Emmanuel Yemi Fagbemiro,3 Olawale Mathias Akinlade,4 Adeseye Abiodun Akintunde,4 Oluwaseun Oyetope Akinpelu,5 Lawrence Aderemi Olatunji,6 Ayodele Olufemi Soladoye,6 Oladimeji George Opadijo4 1Department of Medicine, Lagos State University College of Medicine Ikeja, Lagos, Nigeria; 2Cardiology Unit, BT Diagnostics, LASUTH, Ikeja, Lagos, Nigeria; 3Department of Medicine, College of Medicine, Nile University, Abuja, Nigeria; 4Cardiology Unit, Department of Internal Medicine, LAUTECH Teaching Hospital, Ogbomoso, Nigeria; 5Department of Hematology, LAUTECH Teaching Hospital, Ogbomoso, Nigeria; 6Department of Physiology, University of Ilorin, Ilorin, NigeriaCorrespondence: Adeola Olubunmi Ajibare Tel +234 8033251010Email adeola.ajibare@lasucom.edu.ngBackground: Many specific and non-specific electrocardiographic abnormalities including ventricular arrhythmias have been reported in subjects with sickle cell anemia (SCA). In SCA patients, cardiac electrical abnormalities may be the leading cause of increased risk of arrhythmias. The corrected QT (QTc) interval, peak to the end of the T wave (Tp-e) interval and associated Tp-e/QTc ratio are promising measures of altered ventricular repolarization and increased arrhythmogenesis risk.Aim: This study assessed ventricular repolarization abnormalities in subjects with SCA using the QTc interval, Tp-e interval and Tp-e/QTc ratio, and also evaluated the gender differences in these parameters, as well as their determinants.Methods: Sixty subjects with SCA and 60 healthy control subjects, matched for age and gender, were studied. All participants underwent physical examination, hematological and biochemical evaluation, and 12-lead electrocardiography (ECG) recording. QT and Tp-e intervals were measured from the ECG, and the QTc interval was calculated using Bazett’s formula. Tp-e/QT and Tp-e/QTc ratios were also derived.Results: QT and QTc intervals were prolonged in subjects with SCA. Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio were prolonged in male SCA subjects, with a paradoxical shortening in female SCA subjects. Plasminogen activator inhibitor-1 (PAI-1) was an independent determinant of QTc, while body mass index (BMI) was an independent determinant of both Tp-e interval and Tp-e/QTc ratio.Conclusion: Our results suggest an elevated risk for ventricular arrhythmogenesis in male SCA subjects. Furthermore, increased BMI and PAI-1 level are possible markers of ventricular repolarization abnormalities in SCA subjects.Keywords: arrhythmias, electrocardiography, sickle cell anemia, ventricular repolarization, QTc interval, Tp-e interval

Background: Several animal models are continually being developed to study diabetic complication. Several conflicting regimen for diabetes induction exist in the literature with varying dose strength and regimen for different study interest in diabetes. This study aims to show the effect of high dose streptozotocin (STZ) on the one hand compared with multiple low doses after high fat diet induction on diabetic cardiac autonomic neuropathy (DCAN)., Methodology: Eighty-four Wistar rats were used to demonstrate DCAN induction using 2 approaches one for T1DM (STZ 50mg/kg) and the other for T2DM (HFD for 8 weeks with STZ 25mg/Kg daily for five days). DCAN features were assessed using invasive biomarkers, histology patterns and cardiac nerve densities., Results: Diabetes induction rate was 76% and 89% in T1DM and T2DM model respectively. T1DM group had significant weight loss, reduced c-peptide, and insulin level post induction. The T2DM additionally showed significantly higher total cholesterol and Homeostatic model assessment (HOMA) compared with control. Serum levels of catecholamine, choactase, nerve growth factor and cardiac nerve density confirms development of DCAN., Conclusion: High single dose of STZ and HFD with multiple low doses of STZ may be recommended for DCAN study in T1DM and T2DM rat model respectively., (© 2021 Akinlade OM et al.)

High fat diet (HFD) is a risk factor for metabolic syndrome which is characterized by overt glucose dysmetabolism and tissue derangement. The liver and pancreas are important metabolic tissues with anatomical proximity sharing splanchnic and mesenteric circulation but it is unclear whether, there is an associated metabolic status between the two organs in health and disease. Uric acid (UA) hypersecretion and ectopic lipid accumulation are characteristic pathophysiology of an array of non-communicable diseases. Sodium butyrate (BUT) is reputed for therapeutic roles in metabolic derangement. Therefore, the present study investigated synchrony in hepatic and pancreatic UA and lipid metabolic status in HFD-induced glucose dysregulation and probed the beneficial effects of BUT. Twenty-four female Wistar rats were treated with normal rat chow and distilled water (po) or sodium butyrate (200 mg/kg; po) or high fat diet and distilled water (po) or high fat diet and sodium butyrate. Results showed that HFD increased plasma, pancreatic and hepatic triglyceride, triglyceride-glucose index, malondialdehyde, uric acid (UA), lactate dehydrogenase but reduced glucose-6-phosphate dehydrogenase. Histological analysis revealed hepatic and pancreatic architectural derangement and cellular degeneration in HFD-fed animals. However, BUT reversed the HFD-induced systemic, pancreatic and hepatic synchronous dysmetabolism with evidence of improved histology. HFD-induced lipid and UA alterations were synchronous in the pancreas and liver. BUT elicits beneficial effects on systemic and tissue HFD-induced deleterious metabolic changes which were synchronized in pancreas and liver of rats., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

High fructose intake has been associated with perturbed lipid, uric acid and lactate homeostasis. However, consumption of fructose-sweetened beverages is not usually regulated during pregnancy. The effect of short-chain fatty acid (acetate) on the metabolic effects of high fructose intake during pregnancy is not known. We hypothesized that acetate prevents gestational fructose-induced hepatic triglyceride (TG) accumulation by suppressing uric acid and lactate production. Pregnant Wistar rats were randomly separated into three groups (n = 6/group) receiving drinking water (CON), 10 % (w/v) fructose drink (FRU) and 10 % (w/v) fructose with 200 mg/kg (w/w; p.o.) sodium acetate (FRU + ACE) daily for nineteen days. Fructose intake resulted in increased body weight gain, liver weight, fluid intake, visceral fat, insulin resistance, fasting blood glucose, insulin, plasma and hepatic TG, total cholesterol, free fatty acid, lipid peroxidation, adenosine deaminase, xanthine oxidase, uric acid, lactate, lactate dehydrogenase, and liver injury marker enzymes. However, gestational high fructose intake led to depressed plasma and hepatic glucose-6-phosphate dehydrogenase (G6PD)-dependent antioxidant barrier, adenosine and food intake. All these effects except water intake and food intake were abated by sodium acetate. These results demonstrate that maternal fructose-enriched drink would cause hepatic TG accumulation that is associated with perturbed glucose, uric acid, lactate homeostasis, and G6PD-dependent antioxidant barrier. These results also demonstrate that acetate protects the liver against gestational fructose-induced TG accumulation by inhibiting uric acid and lactate production. Thus, acetate may be useful in the treatment of hyperuricemia- and hyperlactatemia-related disorders., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Cigarette smoking or nicotine replacement therapy has been associated with cardiometabolic disorders (CMD). Hyperuricemia has been implicated in the pathogenesis of CMD and cardiorenal dysfunction. Gut microbiota-derived short chain fatty acids (SCFAs) have been reported to have beneficial glucoregulatory and cardiorenal protective effects. This study aimed at investigating the effect of acetate, a gut-derived SCFA, on nicotine-induced CMD and associated cardiorenal dysmetabolism., Materials and Method: Twenty-four male Wistar rats (n = 6/group) were grouped as: vehicle (p.o.), nicotine-exposed (1.0 mg/kg; p.o.), and sodium acetate-treated (200 mg/kg; p.o.) with or without nicotine exposure daily for 6 weeks. Glucose regulation was evaluated by oral glucose tolerance test and homeostatic model assessment of insulin resistance. Cardiac and renal triacylglycerol (TG), lactate, nitric oxide (NO), uric acid (UA) levels, lactate dehydrogenase (LDH), creatine kinase (CK), adenosine deaminase (ADA), and xanthine oxidase (XO) activities were measured., Results: The CMD were confirmed in the nicotine-exposed rats that exhibited lower body weight, insulin resistance, endothelial dysfunction, glucose intolerance, increased cardiac and renal TG, TG/HDL-cholesterol, UA, lactate, lipid peroxidation, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, LDH, CK, ADA and XO activities. Concurrent treatment with acetate prevented nicotine-induced glucometabolic and cardiorenal alterations., Conclusion: In summary, these results implied that nicotine exposure caused glucometabolic dysregulation and surplus lipid deposit in the heart and kidney through increased UA production and CK activity. Therefore, oral acetate administration prevents cardiorenal lipotoxicity and glucometabolic dysregulation via suppression of UA production and CK activity in nicotine-exposed rats., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Context: Estrogen-progestin combined oral contraceptive (COC) has been connected to mineralocorticoid receptor (MR) activation and adverse cardiometabolic events. We consequently hypothesised that insulin resistance (IR), hyperuricemia, and elevated circulating GSK-3 induced by COC is through activation of MR via mineralocorticoid and glucocorticoid pathways. Methods: Female Wistar rats aged 12 weeks received ( po ) vehicle and COC (1.0   μg ethinylestradiol plus 5.0   μg levonorgestrel) with or without MR blocker (0.25   mg/kg spironolactone; Spl), daily for eight   weeks. Results: Data showed that COC treatment led to increased IR, 1-hour postload glucose level, insulinemia, triglyceride/HDL-cholesterol ratio, total cholesterol/HDL-cholesterol ratio, uric acid, GSK-3, aldosterone, corticosterone values, impaired glucose tolerance and pancreatic β-cell function. However, MR blockade by Spl ameliorated all these alterations except that of aldosterone. Conclusion: The results demonstrate that COC induces IR, hyperuricemia and high GSK-3 levels through activation of MR via glucocorticoid dependent pathway.

We hypothesised that TG/HDL-C ratio and PAI-1 would be associated with high pulse pressure (PP) in young adults with sickle cell trait (SCT) and sickle cell disease (SCD). We compared the clinical, biochemical, and cardiometabolic parameters among individuals with normal genotype (HbAA; n  = 60), SCT (HbAS; n  = 60), and SCD (HbSS; n  = 60), all in steady state. Using multivariate linear regression analysis, high PP was positively related to TG/HDL-C ratio in SCT (β = 0.307; p  = .014) and PAI-1 (β = 0.499; p  = .001) in SCD. The curve of receiver operating characteristic also showed that TG/HDL-C ratio and PAI-1 are efficient predictors of high PP in SCT carriers and SCD patients, respectively. This study suggests that increased levels of TG/HDL-C ratio and PAI-1 may be salient risk factors that would promote the development of arterial stiffness and other CVD in SCT carriers and SCD patients.

Fatty liver is the hepatic consequence of chronic insulin resistance (IR) and related syndromes. It is mostly accompanied by inflammatory and oxidative molecules. Increased activity of xanthine oxidase (XO) exerts both inflammatory and oxidative effects and has been implicated in metabolic derangements including non-alcoholic fatty liver disease. Short chain fatty acids (SCFAs) elicit beneficial metabolic alterations in IR and related syndromes. In the present study, we evaluated the preventive effects of a SCFA, acetate, on nicotine-induced dysmetabolism and fatty liver. Twenty-four male Wistar rats (n = 6/group): vehicle-treatment (p.o.), nicotine-treated (1.0 mg/kg; p.o.), sodium acetate-treated (200 mg/kg; p.o.) and nicotine + sodium acetate-treated groups. The treatments lasted for 8 weeks. IR was estimated by oral glucose tolerance test and homeostatic model assessment of IR. Plasma and hepatic free fatty acid, triglyceride (TG), glutathione peroxidase, adenosine deaminase (ADA), XO and uric acid (UA) were measured. Nicotine exposure resulted in reduced body weight, liver weight, visceral adiposity, glycogen content and glycogen synthase activity. Conversely, exposure to nicotine increased fasting plasma glucose, lactate, IR, plasma and hepatic TG, free fatty acid, TG/HDL-cholesterol ratio, lipid peroxidation, liver function enzymes, plasma and hepatic UA, XO and ADA activities. However, plasma and hepatic glucose-6-phosphate dehydrogenase-dependent antioxidant defense was not affected by nicotine. Concomitant treatment with acetate ameliorated nicotine-induced effects. Taken together, these results indicate that nicotine exposure leads to excess deposition of lipid in the liver by enhancing XO activity. The results also imply that acetate confers hepatoprotection and is accompanied by decreased XO activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hyperuricemia has been implicated in the pathogenesis and complications of cardiovascular diseases with associated elevated oxidant events. There is evidence that excessive salt intake results in cardiometabolic disturbances but the mechanism is elusive. Also, Stigma maydis (corn silk) is noted for its antioxidant properties among other beneficial roles. This study, therefore, aimed to establish the effect of high-salt diet (SD) on uric acid (UA) production and the role of S. maydis in salt-induced phenotypes. Four groups of randomly selected rats ( n = 5) were fed with normal rat feed, corn silk extract (500 mg/kg), SD (8%) and corn silk extract plus high-salt feed. After 6 weeks of the experimental procedure, each animal was anesthetized by exposure to chloroform vapor and blood samples collected by cardiac puncture. Data were expressed in means ± SEM and p values <0.05 were accepted as significant. SD resulted in reduced plasma superoxide dismutase (SOD), nitric oxide (NO), and glutathione peroxidase (GPx) but not endothelial nitric oxide synthase. Also, plasma UA and vascular cell adhesion molecule-1 (VCAM-1) increased in the SD group compared with control. However, S. maydis extract in the SD-exposed group increased NO and GPx and not SOD. Also, S. maydis extract attenuated UA and VCAM-1. In conclusion, high-salt intake may initiate deleterious cardiovascular events through UA-dependent mechanism and S. maydis extract has therapeutic potential in high-salt-induced oxidative damage and/or UA-dependent endothelial pathologies.

Polycystic ovarian syndrome (PCOS) is the most common endocrinological disorder in women of reproductive age and hyperandrogenism is a prominent feature of PCOS resulting in infertility and increased risk of developing metabolic disorders including insulin resistance (IR), abdominal adiposity, glucose intolerance and cardiovascular diseases. Spironolactone (SPL), a non-selective mineralocorticoid receptor (MR) antagonist, has been in wide clinical use for several decades. In this study, we investigated the effects of SPL on IR and metabolic disturbances in letrozole-induced PCOS rats. Eighteen adults female Wistar rats were randomly divided into 3 groups and treated with vehicle, letrozole (LET; 1 mg/kg) and LET + SPL (SPL; 0.25 mg/kg), p.o. once daily for 21 consecutive days. Results showed that LET treatment induced PCOS characterised by elevated plasma testosterone and luteinizing hormone (LH) accompanied with increased body weight and visceral adiposity, IR, glucose intolerance, dyslipidemia and altered histomorphological ovaries. Treatment with SPL however attenuated the elevated testosterone in LET-induced PCOS model accompanied with a reversal in all the observed alterations. Taken together, analysis of the physical, biochemical and histological evidences shows that the protective effect of this very low dose spironolactone may be through its anti-androgenic mechanism., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Women have a lower incidence of cardiovascular diseases (CVD) than men at a similar age but the reverse is the case after menopause, indicating a possible protective effect of estrogen on cardiometabolic function. Although various hormonal therapies have been formulated to combat the CVD risks in postmenopausal state, the beneficial effects have not been consistent. Obesity with insulin resistance (IR) is closely linked to CVD risks while ovariectomized rodents have been shown to mimic a state of obesity and IR. We therefore hypothesized that low-dose spironolactone would ameliorate obesity and IR in estrogen-deprived rats by replenishing estrogen and suppressing elevated glycogen synthase kinase-3 (GSK-3). Ten-week-old female Wistar rats were divided into 4 groups: sham-operated (SHM), spironolactone (SPL; 0.25 mg/kg), and ovariectomized (OVX) rats treated with or without spironolactone daily for 8 weeks. Results showed that estrogen deprivation through ovariectomy caused increased body mass gain and visceral adiposity that are accompanied by increased HOMA-IR, HOMA-β, 1-hour postload glucose, glucose intolerance, platelet/lymphocyte ratio, plasma insulin, atherogenic dyslipidemia, uric acid, GSK-3, corticosterone, and aldosterone and depressed 17β-estradiol. However, treatment of OVX rats with spironolactone ameliorated all these effects. Taken together, the results demonstrate that treatment with low-dose spironolactone improves obesity and IR, which appears to involve replenishment of estrogen and suppression of GSK-3 along with circulating mineralocorticoid and glucocorticoid. The findings imply a positive cardiometabolic effect of low-dose spironolactone usage in estrogen-deprived conditions.

Estrogen deficiency has been associated with increased incidence of cardiovascular diseases , and recent clinical trials of standard formulations of hormonal therapies have not demonstrated consistent beneficial effects. Estrogen-progestin therapy has been used as exogenous estrogen to normalize depressed estrogen level during menopause. Ovariectomized rodents mimic an estrogen-deficient state in that they develop cardiometabolic dysfunction, including insulin resistance (IR). We therefore hypothesized that hormonal therapy with combined oral contraceptive steroids, ethinylestradiol-levonorgestrel (EEL), improves IR, obesity, and glycogen synthase kinase-3 (GSK-3) through reduction of circulating mineralocorticoid in ovariectomized rats. Twelve-week-old female Wistar rats were divided into 4 groups: sham-operated (SHM) and ovariectomized (OVX) rats were treated with or without EEL (1.0 μg ethinylestradiol and 5.0 μg levonorgestrel) daily for 8 weeks. Results showed that OVX or SHM + EEL treated rats had increased HOMA-IR (homeostatic model assessment of IR), 1 h postload glucose, HOMA-β, triglycerides (TG), total cholesterol (TC), TC/HDL cholesterol, TG/HDL cholesterol, plasma insulin, GSK-3, corticosterone, and aldosterone. On the other hand, OVX + EEL treatment ameliorated all these effects except that of aldosterone. Taken together, the results demonstrate that oral hormonal replacement with EEL improves IR and pancreatic β-cell function and suppresses GSK-3 and glucocorticoid independent of circulating aldosterone, suggesting a positive cardiometabolic effect of oral EEL therapy in estrogen-deficient rats.

Background: A seemingly interesting observation in patients with sickle cell anaemia (SCA) is that they usually have lower systemic blood pressures (BP) and insulin resistance than persons in the general population in spite of chronic inflammation and vasculopathy. However, relative systemic hypertension (rHTN) has been linked to pulmonary hypertension, increased blood viscosity and renal insufficiency, which could indicate a risk of developing cardiometabolic disorder (CMD) in SCA.We therefore hypothesized that neck circumference (NC) and CMD marker; triglyceride glucose (TyG) index would independently predict rHTN in young adults with SCA in steady state., Methods: We compared the anthropometrical, hematological, hemorheological and CMD markers between SCA patients with normal BP < 120/70 mmHg; nHTN, n  = 65) and those with rHTN (BP ≥ 120/70 mmHg, n  = 32)., Results: Our results showed that SCA with rHTN had significantly higher body weight, waist circumference, NC, plasma viscosity, systolic and diastolic BP. Results also indicated that NC (OR: 2.98; 95% CI 1.46 to 6.10, p  < 0.01) was a predictor of rHTN in SCA independent of gender, age, weight, waist circumference, BMI, blood viscosity, triglyceride or TyG. A receiver operating characteristic curve analysis also showed that NC was the most efficient predictor of rHTN than other CMD markers., Conclusion: The present study demonstrates that increased NC is a salient risk factors that is independently associated with rHTN in SCA. The finding therefore underscores the utility of NC in early detection and stratification of systemic hypertension, particularly in individuals with SCA., Competing Interests: The study was approved by the Ethical Review. Committees of UITH and LAUTECH Teaching Hospital. All patients were informed about thepurpose and procedures of the study, and gave their written consent. The study was conducted in accordance with the guidelines set by the Declaration of Helsinki on the protection of the rights of human subjects.All patients were informed, and gave consent for the findings of this study to be published.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Context: Elevated gestational circulating testosterone has been associated with pathological pregnancies that increase the risk of development of cardiometabolic disorder in later life., Objective: We hypothesised that gestational testosterone exposure, in late pregnancy, causes glucose deregulation and atherogenic dyslipidaemia that would be accompanied by high plasminogen activator inhibitor-1 (PAI-1). The study also hypothesise that low-dose spironolactone treatment would ameliorate these effects., Methods: Pregnant Wistar rats received vehicle, testosterone (0.5 mg/kg; sc), spironolactone (0.5 mg/kg, po) or testosterone and spironolactone daily between gestational days 15 and 19., Results: Gestational testosterone exposure led to increased HOMA-IR, circulating insulin, testosterone, 1-h post-load glucose, atherogenic dyslipidaemia, PLR, PAI-1 and MDA. However, all these effects, except that of circulating testosterone, were ameliorated by spironolactone., Conclusions: These results demonstrate that low-dose spironolactone ameliorates glucose deregulation and atherogenic dyslipidaemia during elevated gestational testosterone exposure, at least in part, by suppressing elevated PAI-1.

Background: Reports showed that estrogen-progestin oral contraceptive (COC) or tobacco smoking causes increased risk of cardiovascular diseases (CVD) in premenopausal women. Studies also suggest that nicotine, a major tobacco alkaloid, may worsen or improve atherothrombotic CVD. Altered hemorheology, prothrombotic and pro-inflammatory biomarkers, have been implicated in the development of atherothrombotic CVD events. However, the effect of non-smoking nicotine exposure on these biomarkers during COC treatment is not yet established. We therefore sought to determine the effects of nicotine exposure during COC treatment on these biomarkers, and also tested the hypothesis that the nicotine effects would be glucocorticoid-dependent., Methods: Female Sprague-Dawley rats aged 10 weeks were given (po) vehicle, low-dose nicotine (0.1mg/kg) or high-dose nicotine (1.0mg/kg) with or without COC steroids (5.0μg/kg ethinylestradiol and 25.0μg/kg levonorgestrel) daily for 6 weeks., Results: COC treatment or nicotine exposure led to increased insulin resistance (IR), hemorheological (blood viscosity, hematocrit and plasma viscosity), prothrombotic (plasminogen activator inhibitor-1), pro-inflammatory (uric acid, C-reactive protein, neutrophil/lymphocyte and platelet/lymphocyte ratios) biomarkers and corticosterone. However, these effects except that on corticosterone were abrogated by nicotine exposure during COC treatment., Conclusions: Our study indicates that nicotine- or COC-induced IR may be mediated via inflammatory/thrombotic pathway. The results imply that nicotine exposure could impact negatively on atherothrombotic biomarkers in COC non-users, whereas the impact in COC users could be positive. The results also suggest that the anti-inflammatory, antithrombotic and blood viscosity-lowering effects of nicotine exposure during COC use is circulating glucocorticoid-independent., (Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.)

The ketogenic diet (KD) is a cheap and effective alternative therapy for most epilepsy. There are paucity of experimental data in Nigeria on the usefulness of KD in epilepsy models. This is likely to be responsible for the poor clinical acceptability of the diet in the country. This study therefore aimed at providing experimental data on usefulness of KD on seizure models.  The study used 64 Wistar rats that were divided into two dietary groups [normal diet (ND) and ketogenic diet (KD)]. Animal in each group were fed for 35days. Medium chain triglyceride ketogenic diet (MCT-KD) was used and it consisted of 15% carbohydrate in normal rat chow long with 5ml sunflower oil (25% (v/w). The normal diet was the usual rat chow. Seizures were induced with one of Pentelyntetrazole (PTZ), 4-Aminopyridine (AP) and Strychnine (STR). Fasting glucose, ketosis level and serum chemistry were determined and seizure parameters recorded. Serum ketosis was significantly higher in MCT-KD-fed rats (12.7 ±2.6) than ND-fed (5.17±0.86) rats. Fasting blood glucose was higher in ND-fed rats (5.3±0.9mMol/l) than in MCT-KD fed rats (5.1±0.5mMol/l) with p=0.9. Seizure latency was significantly prolonged in ND-fed compared with MCT-KD fed rats after PTZ-induced seizures (61±9sec vs 570±34sec) and AP-induced seizures (49±11sec vs 483±41sec). The difference after Str-induced seizure (51±7 vs 62±8 sec) was not significan. The differences in seizure duration between ND-fed and MCT-KD fed rats with PTZ (4296±77sec vs 366±46sec) and with AP (5238±102sec vs 480±67sec) were significant (p<0.05), but not with STR (3841±94sec vs 3510±89sec) respectively. The mean serum Na+ was significantly higher in MCT-KD fed (141.7±2.1mMol/l) than ND-fed rats (137±2.3mMol/l). There was no significant difference in mean values of other serum electrolytes between the MCT-KD fed and ND-fed animals. MCT-KD caused increase resistance to PTZ-and AP-induced seizures, but has no effect on STR-induced seizures. This antiseizure property is probably mediated through GABAergic receptors (PTZ effect) and blockade of membrane bound KATP channels (AP effect) with some enhancement by serum ketosis.

Objective: Phytochemical constituents as well as antimalarial and toxicity potentials of the methanolic extract of the husk fibre of Dwarf Red variety of Cocos nucifera were evaluated in this study., Methods: The dried powdered husk fibre was exhaustively extracted with hexane, ethyl acetate and methanol successively and the methanolic extract was screened for flavonoids, phenolics, tannins, alkaloids, steroids, triterpenes, phlobatannins, anthraquinones and glycosides. A 4-day suppressive antimalarial test was carried out using Plasmodium berghei NK65-infected mice, to which the extract was administered at doses of 31.25, 62.5, 125, 250 and 500 mg/kg body weight (BW). Toxicity of the extract was evaluated in rats using selected hematological parameters and organ function indices after orally administering doses of 25, 50 and 100 mg/kg BW for 14 d., Results: Phytochemical analysis revealed the presence of alkaloids, tannins, phenolics, saponins, glycosides, steroids and anthraquinones in the extract. Moreover, the extract reduced parasitemia by 39.2% and 45.8% at doses of 250 and 500 mg/kg BW respectively on day 8 post-inoculation. Various hematological parameters evaluated were not significantly altered (P>0.05) at all doses of the extract, except red blood cell count which was significantly elevated (P<0.05) at 100 mg/kg BW. The extract significantly increased (P<0.05) urea, creatinine, cholesterol, high-density lipoprotein-cholesterol and bilirubin concentrations in the serum as well as atherogenic index, while it reduced albumin concentration significantly (P<0.05) at higher doses compared to the controls. Alanine aminotransferase activity was reduced in the liver and heart significantly (P<0.05) but was increased in the serum significantly (P<0.05) at higher doses of the extract compared to the controls., Conclusion: The results suggest that methanolic extract of the Dwarf red variety has partial antimalarial activity at higher doses, but is capable of impairing normal kidney and liver function as well as predisposing subjects to cardiovascular diseases.

In this study, the antimalarial and toxicity potentials of husk fibre extracts of five Nigerian varieties of Cocos nucifera were evaluated in vitro. The only active extract fraction, West African Tall (WAT) ethyl acetate extract fraction, was then evaluated for its phytochemical constituents, antimalarial and toxicity potentials at varying doses (31.25-500 mg/kg body weight) using various organ function indices. The results revealed that WAT ethyl acetate extract fraction (WATEAEF) contained alkaloids, tannins, and flavonoids and was active against Plasmodium falciparum W2 strain maintained in continuous culture, with a selectivity index of 30.3. The same extract fraction was active in vivo against Plasmodium berghei NK65, causing more than 50% reduction in parasitaemia on days 4 and 6 after inoculation at various doses administered. WATEAEF did not significantly alter (P > 0.05) function indices of the liver and cardiovascular system at all doses administered but significantly increased (P < 0.05) plasma creatinine concentration at 250 and 500 mg/Kg body weight compared to controls. The results of this study suggest that WATEAEF possesses antimalarial activity and may not adversely affect normal liver function nor predispose subjects to cardiovascular diseases but may impair normal kidney function at higher doses. Further studies are underway to isolate the active principles.

The leaves of Acalypha wilkesiana are commonly used for the treatment of pain, fever and ulcer by traditional medical practitioners without any scientific data to evaluate the appropriateness of some of the practices. Therefore, this study was carried out to determine whether the ethanol extract of Acalypha wilkesiana has analgesic, anti-inflammatory and antipyretic as well as anti-ulcer effects. The hot plate latency assay and formalin- induced paw licking models were used to evaluate analgesic effects. Animals were divided into groups comprising of five rats each. There were control (administered saline) and reference (administered indomethacin) groups. Also there were three extract groups administered 25, 50 or 100 mg/Kg body weight of extracts. Ulcer was induced using absolute ethanol followed by pylorus ligation in all animals; inflammation was induced using carrageenan while pyrexia was induced by injecting brewer's yeast intramuscularly into the dorsal part of the abdominal cavities of the rats. Different sets of rats were used for the anti-ulcer, anti-inflammatory and antipyretic studies although animal grouping for extract administration were as in analgesic studies. The results show that the extract produced dose-dependent and significant (p<0.05) analgesic and anti-inflammatory activities. The extract also significantly protected against ethanol induced ulcer. Likewise, the extract significantly (p<0.05) reduced the pyretic states of the animals. This study has therefore further provides evidences that may support the ethnomedicinal uses of the ethanolic extracts of Acalypha wilkesiana leaves.

Objective: The aim of the study is to investigate the effects of honey on acute and chronic inflammations and nitric oxide production in rats., Methods: Carrageenan, cotton pellet and formaldehyde methods were used in quantifying the anti-inflammatory effect of honey while the effect of honey on nitric oxide (NO) production was investigated by administering NG-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg body weight, subcutaneously) and L-arginine (300 mg/kg body weight, intraperitoneally) to groups of rats. Animals were divided into five groups each comprising of five rats in each experiment; two groups were orally administered distilled water (control) and indomethacin (5 mg/kg body weight), respectively, while the remaining three groups were administered 2, 6 and 10 g/kg honey for anti-inflammatory studies., Results: Honey significantly (P<0.05) reduced the paw size in the carrageenan model, while in the cotton pellet model, the granuloma weight was significantly (P<0.05) reduced. Honey also significantly (P<0.05) reduced the arthritis induced by formaldehyde injection from the second day of the study. In the investigation on NO involvement, L-NAME significantly inhibited paw oedema while the administration of L-arginine abolished the anti-inflammatory effect of honey and L-NAME., Conclusion: The results obtained from the study confirm that honey has an anti-inflammatory effect which may be due in part to inhibition of NO release. Therefore honey may be used to treat certain acute and chronic inflammatory conditions.

The effects of high calcium diet on body weight in OC treated rats are unknown. This study therefore investigated the effect of increasing dietary calcium from 0.9% to 2.5% on body weight, food ingestion, water intake, heart weight index and renal weight index in female Sprague-Dawley rats treated with a combination of OC steroids (ethinyloestradiol + norgestrel). The rats were assigned into three groups of average of 11 rats each; control, OC-treated and OC + Calcium &ndash; treated groups and administered orally for 10 weeks. Food and water intake, body weight, cardiac weight index, left ventricular weight index, renal weight index and serum calcium level were determined. The result shows that OC treated rats had significantly lower serum calcium concentration, body weight gain, food, water and calcium intake than those of the control rats. The OC + Calcium &ndash; treated rat had significantly higher serum calcium concentration, food, water and calcium intake but significantly lower body weight than those of the OC - treated rats. OC + Calcium - treated rats had significantly higher water intake, calcium intake and significantly lower body weight and food intake when compared with the control rats. Cardiac weight index and renal weight index was comparable in all groups. In conclusion, combined OC-induced reduction in weight gain might be associated with inhibition of the feeding center and consequent inhibition of the thirst center. Co-administration of dietary calcium augmented the reduction in weight gain seen in OC-treated rats probably by further suppression of the feeding and thirst centers.

The present study sought to investigate the effects of prostaglandins synthesis inhibition with indomethacin on blood pressure, heart rate, cardiac weight, plasma electrolytes and cardiovascular responses to arterial baroreceptor stimulation in Oral contraceptive (OC) treated female Sprague-Dawley rats. Oral administration of synthetic oestrogen, ethinyl oestradiol in combination with progestogen, norgestrel for ten weeks significantly increased blood pressure and cardiac weight compared with those of the control rats. Concomitant treatment with indomethacin significantly abrogated increase in blood pressure but did not affect the increase in cardiac weight induced by OC. Heart rate, plasma sodium and potassium concentrations were not affected by OC and/or indomethacin treatment. OC treatment did not alter sympathetic-mediated pressor and tachycardiac responses caused by bilateral carotid baroreceptors unloading. However, these responses were significantly attenuated by indomethacin treatment. These results demonstrated that rat model of OC-induced high blood pressure developed cardiac hypertrophy that is not associated with altered sympathetic-mediated cardiovascular responses to arterial baroreceptor stimulation. The finding that indomethacin prevented OC-induced high blood pressure, but not associated cardiac hypertrophy implies that synthesis of prostaglandins may be an important determinant of OC-induced hypertension, while associated cardiac hypertrophy may not be pressure overload-dependent.

Cardiovascular complications are the major clinical challenges among users of synthetic steroids in oral contraceptive (OC) formulations. Interventions that reduce blood volume and improve vasorelaxation have been shown to reduce hypertension and the associated risk factors. The aim of the present study was to investigate the influence of increasing dietary calcium from 0.9 to 3.0% on the development of OC-induced high blood pressure and associated changes in female Sprague-Dawley rats treated with a combination of OC steroids (1 microg ethinyl estradiol and 10 microg norgestrel; p.o.) daily for 10 weeks. Results showed that OC administration led to significant increases in blood pressure, blood volume and cardiac weight. Conversely, OC caused significant reductions in body weight, urinary excretion of water, plasma levels of calcium, 17beta-estradiol and progesterone. Increased dietary calcium attenuated the elevation in blood pressure induced by OC and abrogated the associated changes in blood volume, cardiac weight, plasma calcium and urinary excretion of water. The endothelium-dependent relaxation responses to acetylcholine and endothelium-independent relaxation responses to sodium nitroprusside in noradrenaline-precontracted aortic rings were not significantly different among the groups. The results indicate that increased calcium intake abrogated the development of high blood pressure and associated increased blood volume and cardiac weight during OC treatment. The beneficial effect of increased dietary calcium during OC use may be explained by improved diuretic and preserved vasorelaxant responses., (2009 Elsevier Inc. All rights reserved.)

The incidence of vascular disorders is markedly lower in cycling, pre-menopausal women and post-menopausal women receiving estrogen-progestogen therapy than in men or untreated postmenopausal women. Clinical studies demonstrate that estrogen-progestogen therapy in pre-menopausal women is associated with increased arterial vascular risk. However, the mechanism of estrogen-progestogen therapy in arterial vascular complications remain unclear. Therefore, the present study aimed at investigating whether chronic administration of combined oral contraceptive (OC) containing progestogen with androgenic property alters endothelium-dependent relaxation responses of the aorta to histamine and acetylcholine. The experiments have been studied on aortic rings obtained from vehicle-treated and OC-treated female Sprague-Dawley rats. Isometric reactivity of aortic rings was recorded with a strain gauge transducer. The maximum contractile response of the aortic rings to noradrenaline in the OC-treated group was not significantly different from that in the vehicle-treated group. Both acetylcholine and histamine caused relaxation of the noradrenaline pre-contracted aortic rings. The relaxation response to acetylcholine in rings from vehicle-treated and OC-treated rats did not differ significantly, while relaxation response to histamine was significantly attenuated in aortic rings from OC-treated rats. In conclusion, the results from the present study suggest that the increased arterial vascular risk associated with OC administration might involve altered endothelium-dependent relaxation via histaminergic-mediated mechanism, but not via muscarinergic-mediated mechanism.

Ethnopharmacological Relevance: Parquetina nigrescens is a shrub that is commonly used in different parts of West Africa for the treatment of several ailments which includes pain, fever and inflammatory conditions., Aim of the Study: The present study was designed to investigate the analgesic, anti-inflammatory and antipyretic effects of the aqueous extract of Parquetina nigrescens leaves in rats., Materials and Methods: Five groups were used for each study, groups 1 and 5 served as control (saline) and reference (indomethacine) respectively, while groups 2-4 received the extract (50-200 mg/kg) orally. Formalin paw licking and hot plate latency tests were used for analgesic studies. Carrageenan oedema, cotton pellet granuloma and formaldehyde arthritis models were used to quantify the anti-inflammatory activities while the brewer's yeast was used for inducing pyrexia., Results: The results of the analgesic study show that the extract produced significant (p<0.05) analgesia in the hot plate and in the formalin tests. In the anti-inflammatory study, Parquetina nigrescens produced significant (p<0.05) inhibition of the various types of inflammation. The extract also inhibited the pyrexia induced by brewer's yeast., Conclusion: The result justifies the traditional uses of Parquetina nigrescens for the treatment of fever, inflammatory and painful conditions.

Unlabelled: The use of estrogen-progestogen oral contraceptive (OC) is associated with high blood pressure, although mechanisms responsible are still unclear. This study sought to investigate the effects of administration of OC on high blood pressure resulting from nitric oxide (NO) synthesis inhibition in female Sprague-Dawley rats. Rats were given ethinyl estradiol in combination with norgestrel and were treated with NO synthase inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME) in the drinking water or drinking water alone for 6 weeks. OC treatment alone led to a significant increase in blood pressure and positive water balance. Treatment with l-NAME alone resulted in a significant elevation of blood pressure without significant positive water balance. Concomitant treatment with OC and l-NAME produced significant increases in blood pressure and water balance. These magnitudes of increases were significantly greater than those observed in rats treated with OC or l-NAME alone. Treatment with OC did not affect NO biosynthesis with or without concurrent l-NAME treatment. Treatment with OC and/or l-NAME did not significantly affect body weight, food intake, heart rate, cardiac weight/body weight ratio, plasma sodium, glomerular filtration rate and urinary sodium output., Conclusion: These data demonstrate that OC administration resulted in a modest increased blood pressure via enhanced water retention that was not associated with impaired NO synthesis. On the other hand, these results showed that increased blood pressure induced by inhibition of NO synthesis was not associated with water retention. The study also indicated that OC administration aggravated increase in blood pressure during NO synthesis inhibition, via enhanced water retention.

The use of oral contraceptive (OC) steroids is associated with high blood pressure, although mechanisms responsible are still unclear. This study sought to investigate the possible roles that renin-angiotensin system (RAS) and sympathetic nervous system (SNS) may play in the development of OC-induced hypertension. Administration of OC led to significant increases in blood pressure, heart weight and significant decrease in urinary output in OC-treated and OC+clonidine-treated groups but not in OC+captopril-treated group. The pressor response to angiostensin II was significantly greater in the OC-treated rats than in the control rats. However, the pressor responses induced by norepinephrine were not significantly affected by OC administration. The results of the present study demonstrate that OC-induced high blood pressure is associated with cardiac hypertrophy, enhanced pressor response to angiotensin II and preserved pressor response to sympathetic activation. The study also suggests that the development of the OC-induced hypertension and cardiac hypertrophy is mediated by RAS, but not by SNS.

Unlabelled: Estrogen-progestogen oral contraceptive (OC) use is associated with abnormal lipid metabolism, impaired glucose tolerance and high prevalence of vascular complications. OC use has been shown to alter the requirements for folic acid. Therefore, the aim of the present study was to clarify the influence of dietary folic acid on OC-induced impaired glucose tolerance and abnormal plasma lipid profile in female Sprague-Dawley rats. Vehicle-treated and OC-treated rats were fed for 6 weeks with a control diet (750mug folic acid/kg diet) while OC-treated folic acid deficient (FD) rats were fed for 6 weeks with a folic acid-deficient diet (250mug folic acid/kg diet). OC receiving rats were treated with a combination of OC steroids (ethinyl estradiol and norgestrel) by oral gavage. OC treatment resulted in rats receiving folic acid deficient diet in impaired glucose tolerance, decreased high-density lipoprotein (HDL)-cholesterol and increased low-density lipoprotein (LDL)-cholesterol when compared with control rats. However, OC treatment did not result in impaired glucose tolerance or disturbed plasma lipid profile in rats receiving the same folic acid level as the controls. OC treatment led to significant decreases in plasma levels of 17beta-estradiol and testosterone in both groups. OC administration in rats with folic acid deficient diet significantly lower HDL-cholesterol and higher LDL-cholesterol levels while plasma levels of 17beta-estradiol and testosterone were similar in both OC-treated groups., Conclusion: These results demonstrate impaired glucose tolerance and disturbed plasma lipid profile induced by OC treatment in folic acid deficient rats and suggest that inadequate folic acid intake might contribute to increased cardiovascular risk during OC use that could be prevented by proper oral folic acid intake.

The anti-inflammatory activity of an ethanolic extract of Carica papaya leaves was investigated in rats using carrageenan induced paw oedema, cotton pellet granuloma and formaldehyde induced arthritis models. Experimental animals received 25-200 mg/Kg (orally) of the extracts or saline (control group) and the reference group received 5 mg/ Kg of indomethacin. The ulcerogenic activity of the extract was also investigated. The results show that the extracts significantly (p <0.05) reduced paw oedema in the carrageenan test. Likewise the extract produced significant reduction in the amount of granuloma formed from 0.58 +/-0.07 to 0.22 +/-0.03 g. In the formaldehyde arthritis model, the extracts significantly reduced the persistent oedema from the 4th day to the 10th day of the investigation. The extracts also produced slight mucosal irritation at high doses. The study establishes the anti-inflammatory activity of Carica papaya leaves.

Variation in reproductive status in response to photoperiods has been observed in laboratory rats. We investigated the effects of photoperiod on testicular activity in Sprague-Dawley rats (Rattus norvigicus) maintained in experimental photoperiodic condition. Twenty-four adult male rats weighing 170+/-10g were conditioned to different lighting conditions of Light/Dark (LD) Cycle for 6 weeks. Group 1, Control group (LD12:12, light on from 07:00hr to 19:00hr). Group 2, Short Photoperiod group (LD 8:16hr, light on from 09:00hr to 17:00hr). Group 3, Long Photoperiod group (LD 16:8hr, light on from 05:00hr to 21:00hr). A significant influence of different lighting conditions on the testicular parameters was observed. Short photoperiod showed a suppressing effect (P < 0.001) on testicular weight, sperm motility sperm viability and sperm counts, while long photoperiod had an inducing, though insignificant, effect on the measured parameters. The results confirmed that Sprague-Dawley rats are photoresponsive and changes in the photoperiod could influence their reproductive functions.

Studies that associated oestrogen-progestogen oral contraceptive (OC) use with altered glucose and lipid metabolisms in women did not account for possible influence in dietary magnesium. The use of OC and glucose and lipid metabolism seems to remain a broad public health concern since over 100 million women use OC world wide for a prolonged period of time. The study, therefore, sought to investigate in a female rat model whether or not glucose intolerance and dyslipidaemia associated with OC are influenced by dietary magnesium status. Control and OC- treated rats were maintained on control diet, whereas OC+ Mg- treated rats were on high magnesium diet. OC- treated and OC+Mg treated rats also received a combination of OC steroids, ethinyl oestradiol and norgestrel (orally). When compared with the controls, OC treatment led to significant reduced glucose tolerance and plasma HDL-cholesterol and significant increases in plasma LDL-cholesterol and atherogenic indices in OC- treated rats. Treatment with OC did not result in significant attenuation in these parameters in OC+Mg- treated rats when compared with the controls. In conclusion, these results suggest that impaired glucose tolerance and dyslipidaemia associated with OC use may be prevented by increased dietary magnesium.

Oral contraceptive (OC) steroids use has been associated with variable effects on blood lipid and rheological properties, and abnormal plasma lipid and hemorheological profiles has been shown to be in almost all conditions associated with accelerated atherosclerotic cardiovascular disorders. This study aimed at investigating the effect of increased calcium intake on plasma levels of lipids, malondialdehyde (lipid peroxidation index), free radical defense system and hemorheological variables in OC-treated female Sprague-Dawley rats. OC-treated and OC + Calcium-treated groups received a combination of ethinyl estradiol and norgestrel for 10 weeks by oral gavage. OC + Calcium-treated rats fed on 2.5% calcium diet while other groups fed on 0.9% calcium diet in addition to drinking water ad libitum. Results showed that LDL-cholesterol, total cholesterol/HDL-cholesterol ratio, LDL-cholesterol/HDL-cholesterol ratio, plasma viscosity, hematocrit and plasma fibrinogen were significantly higher while plasma HDL-cholesterol, 17beta-estradiol, testosterone and calcium levels were significantly lower in OC-treated rats when compared with the control rats. The altered plasma lipid and calcium levels were prevented by increased calcium intake, whereas the OC-induced changes in hematocrit, plasma viscosity, fibrinogen, 17beta-estradiol and testosterone were not affected by increased dietary calcium. Plasma lipid peroxidation index, ascorbic acid and albumin levels were comparable in all the groups. The present study demonstrated that OC-induced altered blood lipid and rheological properties were not associated with increased lipid peroxidation. The results also suggest that calcium enriched diet may improve lipid profile but not hemorheological parameters, by a mechanism that is independent of circulating 17beta-estradiol and testosterone in OC-treated rats.

Cardiovascular disorders are the primary causes of morbidity and mortality in patients with diabetes mellitus (DM). Agents that improve lipid profile and reduce oxidative stress have been shown to reduce the ensuing risk factors. In the present study, we investigated whether increased magnesium intake could improve hyperglycaemia, dyslipidaemia, and reduce oxidative stress in alloxan-induced diabetic rats. Male Wistar rats were divided into non-diabetic (ND), diabetic (DM) and diabetic fed on a high magnesium diet (DM-Mg) groups. Plasma concentrations of thiobarbituric acid reactive substances (TBARS) were used as markers of oxidative stress. Plasma levels of ascorbic acid, magnesium and calcium were also determined. Diabetes was induced by injecting alloxan (100 mg/kg B.W). The fasting blood glucose levels were significantly lower in the DM-Mg rats than in the DM rats. Plasma total cholesterol, triglyceride, TBARS levels were significantly higher while plasma HDL-cholesterol, HDL-cholesterol/total cholesterol ratio, ascorbic acid levels were significantly lowered in DM rats compared with the ND rats. Increased intake of magnesium significantly abrogated these alterations. There were no significant differences in the plasma levels of magnesium and calcium between the DM and ND groups. However, plasma levels of magnesium but not calcium were significantly elevated in DM-Mg rats when compared with other groups. In conclusion, these results suggest that diet rich in magnesium could exert cardioprotective effect through reduced plasma total cholesterol, triglyceride, oxidative stress and ameliorated HDL-cholesterol/total cholesterol ratio as well as increased plasma ascorbic acid and magnesium in diabetic rats.