Corrosion of food grinding discs in gastro-intestinal environment.

The need for food size reduction before consumption has led to the use of motorized grinding machine which operates on energized rubbing of two grooved cast-iron discs, and this unintentionally results in tribological degradation and corrosion of grinding discs into the ground food. The objective of this study was to carry out an assessment of corrosion susceptibility of grinding discs from different manufacturing methods in simulated gastro-intestinal environment. Six grinding discs from three states in Nigeria were selected for this study, based on manufacturing methods namely: rotary, cupola, and pit furnaces. Experimental techniques used for the study included: X-Ray Fluorescence spectroscope for determination of chemical composition and X-Ray Diffractometer was used for phase identification. Corrosion susceptibility of grinding discs on interaction with pseudo-body fluid was studied using potentiodynamic polarization scan and product analysis (gasometric) methods in simulated gastro-intestinal environment, typical of human stomach, as electrolyte. The electrolyte contained 2 g/L NaCl acidified to pH of 1.7 with HCl and regulated at 37 °C. Optical microscopy of the electrochemical samples was done for corrosion damage assessment. The key finding from the study was that all the grinding discs contain iron and silicon as dominant alloy elements, which existed predominantly as iron carbide and ferrosilicon phases. Corrosion of the discs in simulated gastric solution was well profound irrespective of the manufacturing method, though, with varying degree among the discs. The outcome of this study is applicable to food industries where cognitive measures may have to be taken on materials selection to minimise the risk of food contamination from materials corrosion.

Sildenafil ameliorates leptin resistance and normalizes lipid handling in the hypothalamic and adipose tissues of testosterone-exposed pregnant rats.

Leptin and hypothalamic-adipose lipid handling are relevant in determining the shift of metabolic activities. There are scanty findings connecting glucose dysregulation as a result of hyperandrogenism during gestation to hypothalamic-adipose axis and leptin resistance. Sildenafil has recently gained attention in the prevention of intra-uterine growth restriction. The present study aimed at demonstrating the effect of sildenafil on leptin resistance and hypothalamic-adipose lipid handling in testosterone-exposed pregnant rats. Three groups of pregnant Wistar rats (n = 5/group) received olive oil (Ctr, S.C.) or testosterone propionate (Tes, 3.0 mg/kg; sc)or testosterone propionate (3.0 mg/kg; sc) and sildenafil (Tes + PDE5, 50 mg/kg; po)from gestational day 14-19. Blood samples, hypothalamus and adipose tissue were excised for biochemical analysis on day 20. Adipose and body weights, plasma leptin and adiponectin, adipose and hypothalamic leptin and triglyceride, adipose uric acid, hypothalamic Nrf2, catalase and nitric oxide were reduced following gestational testosterone exposure. Also, fasting insulin, plasma triglyceride, uric acid, leptin-adiponectin ratio, hypothalamic free fatty acid, total cholesterol, uric acid, aspartate transaminase and cyclic guanine monophosphate were elevated by testosterone exposure to pregnant animals. Sildenafil ameliorated leptin resistance and normalized hypothalamic-adipose lipid handling. Therefore, sildenafil protects against testosterone-induced leptin resistance and adverse hypothalamic-adipose lipid handling in pregnant rats.

Sildenafil augments fetal weight and placental adiponectin in gestational testosterone-induced glucose intolerant rats.

Testosterone induces intra-uterine growth restriction (IUGR) with maternal glucose dysregulation and oxidant release in various tissues. Adiponectin, which modulates the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) signaling is expressed in the placenta and affects fetal growth. Sildenafil, a phosphodiesterase type 5 inhibitor (PDE5i), used mainly in erectile dysfunction has been widely studied as a plausible pharmacologic candidate in IUGR. Therefore, the present study sought to determine the effect of PDE5i on placental adiponectin/Nrf2 pathway in gestational testosterone-induced impaired glucose tolerance and fetal growth. Fifteen pregnant Wistar rats were allotted into three groups (n = 5/group) receiving vehicles (Ctr; distilled water and olive oil), testosterone propionate (Tes; 3.0 mg/kg; sc) or combination of testosterone propionate (3.0 mg/kg; sc) and sildenafil (50.0 mg/kg; po) from gestational day 14-19. On gestational day 20, plasma and placenta homogenates were obtained for biochemical analysis as well as fetal biometry. Pregnant rats exposed to testosterone had 4-fold increase in circulating testosterone compared with control (20.9 ± 2.8 vs 5.1 ± 1.7 ng/mL; p < 0.05) whereas placenta testosterone levels were similar in testosterone- and vehicle-treated rats. Exposure to gestational testosterone caused reduction in fetal and placental weights, placental Nrf2 and adiponectin. Moreover, impaired glucose tolerance, elevated plasma triglyceride-glucose (TyG) index, placental triglyceride, total cholesterol, lactate, malondialdehyde and alanine aminotransferase were observed in testosterone-exposed rats. Treatment with sildenafil improved glucose tolerance, plasma TyG index, fetal and placental weights and reversed placental adiponectin in testosterone-exposed pregnant rats without any effect on placental Nrf2. Therefore, in testosterone-exposed rats, sildenafil improves impaired glucose tolerance, poor fetal outcome which is accompanied by augmented placental adiponectin regardless of depressed Nrf2.

Inhibition of dipeptidyl peptidase-4 averts free fatty acids deposition in the hearts of oral estrogen-progestin contraceptive-induced hyperinsulinemic female rats.

Free fatty acid (FFA) deposition in non-adipose tissues such as the heart is a characteristic of insulin resistant states which feature hyperinsulinemia and dipeptidyl peptidase-4 (DPP-4) activation. Estrogen-progestin oral contraceptives (OC) treatment reportedly increased DPP-4 activity in rat tissue, and DPP-4 inhibitors have anti-diabetic and anti-inflammatory properties. This study aims to investigate the effects of DPP-4 inhibition on cardiac FFA deposition in estrogen-progestin-treated female rats. From our data, estrogen-progestin OC exposure in female rats led to elevated plasma insulin, cardiac DPP-4 activity, FFA and triglyceride (TG) accumulation, TG/high-density lipoprotein cholesterol (TG/HDL-C) ratio, adenosine deaminase/xanthine oxidase/uric acid pathway (ADA/XO/UA), lipid peroxidation, glycogen synthase activity, and alanine phosphatase; whereas cardiac glucose-6-phosphate dehydrogenase, Na+/K+-ATPase and nitric oxide (NO) were decreased. However, DPP-4 inhibition resulted in decreased plasma insulin, cardiac DPP-4 activity, FFA, TG, TG/HDL-C ratio, and alkaline phosphatase. These were accompanied by reduced ADA/XO/UA pathway, lipid peroxidation, and augmented NO and Na+/K+-ATPase in estrogen-progestin OC-treated rats. DPP-4 inhibition attenuated cardiac lipid deposition accompanied by reduced activity in the ADA/XO/UA pathway in estrogen-progestin OC-treated female rats. DPP-4 is therefore a plausible therapeutic target in cardiometabolic disorders.

Sodium acetate ameliorated systemic and renal oxidative stress in high-fructose insulin-resistant pregnant Wistar rats.

Pregnancy is an insulin-resistant condition especially at near term predisposing maternal kidneys to hyperinsulinemia-induced oxidative stress. The impact of fructose on renal metabolic dysregulation and oxidative stress in pregnancy requires elucidation. Short-chain fatty acids (SCFAs) are known for protective roles in oxidative stress conditions. Therefore, the study aimed at investigating fructose-induced glucose dysregulation and renal oxidative stress in pregnant and non-pregnant rats and the possible preventive role of SCFA, acetate. Thirty female Wistar rats were grouped (n = 5/group). Three groups were made pregnant (P); the other three remained non-pregnant (NP). Both pregnant and non-pregnant rats received drinking water (control), 10% fructose (w/v) (NP+F or P+F), and 10% (w/v) fructose plus sodium acetate (200 mg/kg) (NP+F+A or P+F+A) for 3 weeks. Renal and plasma glutathione antioxidant index (GSH/GSSG), G6PDH, and adenosine were significantly lower in NP+F and P+F groups compared with control while renal and plasma adenosine deaminase (ADA), xanthine oxidase (XO), uric acid (UA), lactate dehydrogenase (LDH), and malonaldehyde (MDA) were significantly elevated in NP+F and P+F groups compared with controls. HOMA-IR showed marked impairment in both NP+F and P+F groups. The P+F group revealed greater suppression in plasma and renal G6PDH-dependent antioxidant index, adenosine, and aggravation of LDH, MDA compared with the NP+F group (p < 0.05). Sodium acetate reduces plasma and renal surrogate oxidative stress markers, improved G6PD-dependent antioxidant index, and HOMA-IR in NP+F and P+F groups. Pregnancy exacerbates fructose-induced insulin resistance and renal oxidative stress whereas acetate ameliorated fructose-induced redox and glucose dysregulation in pregnant and non-pregnant rats.

Assessment of Ventricular Repolarization in Sickle Cell Anemia Patients: The Role of QTc Interval, Tp-e Interval and Tp-e/QTc Ratio and Its Gender Implication.

BACKGROUND: 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.

Oral L-glutamine restores adenosine and glutathione content in the skeletal muscle and adipose tissue of insulin-resistant pregnant rats.

OBJECTIVES: Mishandling of lipid and glycogen has been documented as a feature of metabolic tissues in insulin resistance-related disorders. However, reports exist detailing that L-glutamine (GLN) protects non-adipose tissue against the deleterious effects of metabolic disorders. Therefore, we hypothesized that GLN would protect skeletal muscle and adipose tissue against the deleterious effects of lipid and glycogen mishandlings by increasing adenosine and glutathione levels in pregnant rats exposed to fructose (FRU)-enriched drinks. METHODS: Pregnant Wistar rats weighing 150 to 180 g were randomly assigned to control, GLN, FRU, and FRU + GLN groups (six rats/group). The groups received vehicle (P.o.), glutamine (1 g/kg), FRU (10%; w/v), and FRU + GLN, respectively, for 19 d. RESULTS: Data show that FRU caused insulin resistance with corresponding increased blood glucose, circulating and pancreatic insulin levels, and lipid accumulation and glycogen depletion in skeletal muscle, but glycogen accumulation and a decreased lipid profile in adipose tissue. Adenosine and glutathione content decreased, whereas adenosine deaminase, xanthine oxidase, uric acid, and malondialdehyde concentrations increased in both tissues. In addition, glucose-6-phosphate dehydrogenase activity decreased in skeletal muscle but remained unaltered in adipose tissue. However, supplementation with GLN improved perturbed lipid and glycogen with a corresponding increase in adenosine and glutathione. CONCLUSIONS: The present results collectively indicate that lipid and glycogen mishandlings caused by high gestational FRU intake result in the depletion of adenosine and glutathione in skeletal muscle and adipose tissue. These findings also suggest that L-glutamine protects against skeletal muscle and adipose tissue dysmetabolism by enhancing adenosine and glutathione.

L-glutamine ameliorates adipose-hepatic dysmetabolism in OC-treated female rats.

Adipose dysfunction and inflammation with or without hepatic defects underlie metabolic obesity. Glutamine (GLU) improves glucoregulation and metabolic indices but its effects on adipose function and hepatic lipid deposition in estrogen-progestin oral contraceptive (EPOC) users are unknown. Therefore, we hypothesized that GLUT supplementation would protect against adipose dysfunction and excess hepatic lipid influx and deposition in EPOC-treated animals by suppressing adenosine deaminase/xanthine oxidase (ADA/XO) activity and improving glucose-6-phosphate dehydrogenase (G6PD)-dependent antioxidant defense. Female Wistar rats weighing 150-180 g were allotted into control, GLUT, EPOC and EPOC + GLUT groups (six rats/group). The groups received vehicle (distilled water, p.o.), GLUT (1 g/kg), EPOC containing 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel and EPOC plus GLUT, respectively, daily for 8 weeks. Results showed that the administration of EPOC caused glucose dysregulation and increased triglyceride-glucose index and visceral adiposity, but the body weight and liver weight were not affected. However, EPOC significantly decreased adipose lipid, G6PD and glutathione and increased glycogen synthesis, ADA, XO, uric acid, lipid peroxidation, lactate production and gamma-glutamyl transferase activity (GGT). On the other hand, EPOC increased hepatic lipid, ADA, XO, uric acid, lipid peroxidation and lactate production and decreased glycogen synthesis, G6PD and glutathione. Nevertheless, supplementation with glutamine attenuated these alterations. Collectively, the present results indicate that EPOC causes metabolically induced obesity which is associated with adipose dysfunction and hepatic metabolic disturbance. The findings also suggest that glutamine confers metabo-protection with corresponding improvement in adipose and hepatic metabolic function by suppression of ADA/XO activity and enhancement of G6PD-dependent antioxidant defense.

l-glutamine supplementation exerts cardio-renal protection in estrogen-progestin oral contraceptive-treated female rats.

Glycogen and lipid disruptions represent a spectrum of metabolic disorders that are crucial risk factors for cardiovascular disease in estrogen-progestin oral contraceptive (COC) users. l-glutamine (GLN) has been shown to exert a modulatory effect in metabolic disorders-related syndromes. We therefore hypothesized that GLN supplementation would protect against myocardial and renal glycogen-lipid mishandling in COC-treated animals by modulation of Glucose-6-phosphate dehydrogenase (G6PD) and xanthine oxidase (XO) activities. Adult female Wistar rats were randomly allotted into control, GLN, COC and COC + GLN groups (six rats per group). The groups received vehicle (distilled water, p.o.), GLN (1 g/kg), COC containing 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel and COC plus GLN respectively, daily for 8 weeks. Data showed that treatment with COC led to metabolically-induced obesity with correspondent increased visceral and epicardial fat mass. It also led to increased plasma, myocardial and renal triglyceride, free fatty acid, malondialdehyde (MDA), XO activity, uric acid content and decreased glutathione content and G6PD activity. In addition, COC increased myocardial but not renal glycogen content, and increased myocardial and renal glycogen synthase activity, increased plasma and renal lactate production and plasma aspartate transaminase/alanine aminotransferase (AST/ALT) ratio. However, these alterations were attenuated when supplemented with GLN except plasma AST/ALT ratio. Collectively, the present results indicate that estrogen-progestin oral contraceptive causes metabolically-induced obesity that is accompanied by differential myocardial and renal metabolic disturbances. The findings also suggest that irrespective of varying metabolic phenotypes, GLN exerts protection against cardio-renal dysmetabolism by modulation of XO and G6PD activities.

Uric acid is a key player in salt-induced endothelial dysfunction: the therapeutic role of Stigma maydis (corn silk) extract.

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.

Oral L-glutamine rescues fructose-induced poor fetal outcome by preventing placental triglyceride and uric acid accumulation in Wistar rats.

BACKGROUND: Metabolic adaptation of pregnant mothers is crucial for placental development and fetal growth/survival. However, evidence exists that indiscriminate consumption of fructose-enriched drink (FED) during pregnancy disrupts maternal-fetal metabolic tolerance with attendant adverse fetal outcomes. Glutamine supplementation (GLN) has been shown to exert a modulatory effect in metabolic disorders. Nevertheless, the effects of GLN on FED-induced poor fetal outcome, and in particular the impacts on placental uric acid/lipid accumulation are unknown. The present study was conducted to test the hypothesis that oral GLN improves fetal outcome by attenuating placental lipid accumulation and uric acid synthesis in pregnant rats exposed to FED. MATERIALS AND METHODS: Pregnant Wistar rats (160-180 g) were randomly allotted to control, GLN, FED and FED + GLN groups (6 rats/group). The groups received vehicle by oral gavage, glutamine (1 g/kg) by oral gavage, fructose (10%; w/v) and fructose + glutamine, respectively, through gestation. RESULTS: Data showed that FED during pregnancy caused placental inefficiency, reduced fetal growth, and caused insulin resistance with correspondent increase in fasting blood glucose and plasma insulin. FED also resulted in an increased placental triglyceride, total cholesterol and de novo uric acid synthesis by activating adenosine deaminase and xanthine oxidase activities. Moreover, FED during pregnancy led to increased lipid peroxidation, lactate production with correspondent decreased adenosine and glucose-6-phosphate dehydrogenase-dependent antioxidant defense. These alterations were abrogated by GLN supplementation. CONCLUSION: These findings implicate that high FED intake during pregnancy causes poor fetal outcome via defective placental uric acid/triglyceride-dependent mechanism. The findings also suggest that oral GLN improves fetal outcome by ameliorating placental defects through suppression of uric acid/triglyceride accumulation.

Oral ethinylestradiol-levonorgestrel normalizes fructose-induced hepatic lipid accumulation and glycogen depletion in female rats.

The present study investigated the effects of oral ethinylestradiol-levonorgestrel (EEL) on hepatic lipid and glycogen contents during high fructose (HF) intake, and determined whether pyruvate dehydrogenase kinase-4 (PDK-4) and glucose-6-phosphate dehydrogenase (G6PD) activity were involved in HF and (or) EEL-induced hepatic dysmetabolism. Female Wistar rats weighing 140-160 g were divided into groups. The control, EEL, HF, and EEL+HF groups received water (vehicle, p.o.), 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel (p.o.), fructose (10% w/v), and EEL plus HF, respectively, on a daily basis for 8 weeks. Results revealed that treatment with EEL or HF led to insulin resistance, hyperinsulinemia, increased hepatic uric acid production and triglyceride content, reduced glycogen content, and reduced production of plasma or hepatic glutathione- and G6PD-dependent antioxidants. HF but not EEL also increased fasting glucose and hepatic PDK-4. Nonetheless, these alterations were attenuated by EEL in HF-treated rats. Our results demonstrate that hepatic lipid accumulation and glycogen depletion induced by HF is accompanied by increased PDK-4 and defective G6PD activity. The findings also suggest that EEL would attenuate hepatic lipid accumulation and glycogen depletion by suppression of PDK-4 and enhancement of a G6PD-dependent antioxidant barrier.

Glutamine confers renoprotection by normalizing lipid and glutathione content in insulin-resistant pregnant rats.

OBJECTIVE: Increasing consumption of fructose is a major contributor to epidemic metabolic syndrome (MS), and the risk of renal disorders and/or injuries remains high among individuals with MS particularly during pregnancy. Glutamine (GLT) has been demonstrated to have a modulatory effect in MS and/or insulin resistance (IR). This study investigated the effect of GLT on renal lipid accumulation and glutathione depletion induced by high fructose-enriched drink (FED) in pregnant rats and also tested the hypothesis that the renoprotective role of GLT is by suppression of adenosine deaminase (ADA)/xanthine oxidase (XO)/uric acid (UA) pathway. METHODS: Pregnant Wistar rats weighing between 160 and 180 g were allotted into Control, GLT, FED and FED + GLT groups (6 rats/group). The groups received distilled water (vehicle, p. o.), 1 g/kg bw GLT (p.o.), 10% Fructose (w/v) and 10% Fructose (w/v) plus 1 g/kg bw GLT (p.o.) respectively, daily for 19 days. RESULTS: Data showed that FED caused IR, increased body weight gain, blood glucose, plasma insulin, creatinine, urea, lipid accumulation, lipid peroxidation, lactate production, aspartate transaminase and alanine aminotransferase, depressed Glucose-6-phosphate dehydrogenase, sodium-potassium-ATPase activities and glutathione. These alterations were accompanied by increased activity of ADA/XO/UA pathway. However, the FED-induced renal injury and its correlates were normalized by GLT supplementation. CONCLUSION: The present results demonstrate that renal lipid accumulation and glutathione depletion-driven renal injury in pregnant rats is accompanied by increased activity of ADA/XO/UA pathway. The findings also suggest that GLT would confer protection against renal injury by protecting against lipid accumulation and glutathionedepletion, at least in part, through suppression of ADA/XO/UA pathway.

Preventive effects of l-glutamine on gestational fructose-induced cardiac hypertrophy: involvement of pyruvate dehydrogenase kinase-4.

Gestational fructose exposure has detrimental health consequences on both the maternal and fetus or offspring in the early or later life, contributing to epidemic rise in cardiometabolic syndrome including cardiac events. l-Glutamine has been shown to mitigate cardiac metabolic stress. However, the effect of l-glutamine on cardiac hypertrophy induced by gestational fructose exposure is not known. We therefore hypothesized that l-glutamine would prevent gestational fructose-induced cardiac hypertrophy, possibly by suppression of pyruvate dehydrogenase kinase-4 (PDK-4). Pregnant Wistar rats were allotted into the control, l-glutamine, gestational fructose exposure, and gestational fructose exposure plus l-glutamine groups (6 rats in each group). The groups received distilled water (vehicle, per os), 1 g/kg body weight l-glutamine (per os), 10% fructose (w/v) and 10% fructose (w/v) plus 1 g/kg l-glutamine (per os), respectively, daily for 19 days. Data from this study showed that gestational fructose-enriched drink caused cardiac hypertrophy with correspondent body weight gain, glucose dysregulation, increased cardiac PDK-4, triglyceride, glycogen, lactate, and uric acid production. On the other hand, defective glutathione-dependent antioxidant barrier was also observed in pregnant rats taking fructose-enriched drink. However, the gestational fructose-induced cardiac hypertrophy and its correlates were attenuated by l-glutamine. The present results demonstrate that gestational fructose-enriched drink induces cardiac hypertrophy that is accompanied by increased PDK-4. The findings also suggest that the inhibitory effect of l-glutamine on PDK-4 prevents the development of cardiac hypertrophy, thereby implying that PDK-4 may be a potential novel therapeutic intervention for cardiac hypertrophy especially in pregnancy.

Sodium acetate improves disrupted glucoregulation and hepatic triglyceride content in insulin-resistant female rats: involvement of adenosine deaminase and dipeptidyl peptidase-4 activities.

Combined oral contraceptive (COC) treatment has been shown to be associated with glucose deregulation and increased triglyceride levels, but the mechanisms are elusive. Soluble dipeptidyl peptidase-4 (sDPP-4) and adenosine deaminase (ADA) are involved in the initiation and/or progression of cardiometabolic disorders. We therefore, hypothesized that increased DPP-4 and ADA activities are involved in glucose deregulation and hepatic triglyceride accumulation induced by COC treatment. This study also investigated whether short-chain fatty acid, acetate, would protect against COC-induced dysmetabolic effects. Female Wistar rats received (p.o.) vehicle and COC (1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel) with or without sodium acetate (ACE; 200 mg) for 8 weeks. Treatment with COC led to increased plasma triglyceride-glucose index, 1-h postload glucose response, insulin, free fatty acid, insulin resistance, and impaired glucose tolerance. COC treatment also resulted in increased plasma and hepatic triglycerides (TG), TG/HDL-cholesterol ratio, malondialdehyde, uric acid, lactate dehydrogenase, DPP-4, ADA, and xanthine oxidase (XO) activities. On the other hand, COC led to reduction in nitric oxide level. However, ACE significantly ameliorated the alterations induced by COC treatment, but XO activity remains elevated during COC treatment. This result also demonstrates that increased DPP-4 and ADA activities are at least in part involved in glucose deregulation and hepatic TG accumulation induced by COC treatment. Therefore, sodium acetate would impact positively on cardiometabolic disorders, at least in part, by inhibition of DPP-4 and ADA activities.

Oral ethinylestradiol-levonorgestrel attenuates cardiac glycogen and triglyceride accumulation in high fructose female rats by suppressing pyruvate dehydrogenase kinase-4.

Fructose (FRU) intake has increased dramatically in recent decades with a corresponding increased incidence of insulin resistance (IR), particularly in young adults. The use of oral ethinylestradiol-levonorgestrel (EEL) formulation is also common among young women worldwide. The present study aimed at determining the effect of EEL on high fructose-induced cardiac triglyceride (TG) and glycogen accumulation. The study also investigated the possible involvement of pyruvate dehydrogenase kinase-4 (PDK-4) in EEL and/or high fructose metabolic effects on the heart. Ten-week-old female Wistar rats were allotted into four groups. The control, EEL, FRU, and EEL + FRU rats received distilled water (vehicle, p.o.), 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel (p.o.), 10% fructose (w/v), and 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel and 10% fructose, respectively, daily for 8 weeks. Data showed that EEL or high fructose caused IR' impaired glucose tolerance' hyperlipidemia' increased plasma lactate, lactate dehydrogenase, PDK-4, uric acid, xanthine oxidase (XO), adenosine deaminase (ADA), malondialdehyde (MDA), cardiac uric acid, TG, TG/HDL- cholesterol, glycogen synthesis, MDA, and visceral fat content and reduced glutathione. High fructose also resulted in impaired pancreatic ß-cell function, hyperglycemia, and increased cardiac PDK-4, lactate synthesis, and mass. Nonetheless, these alterations were ameliorated in EEL plus high fructose rats. This study demonstrates that high fructose-induced myocardial TG and glycogen accumulation is attributable to increased PDK-4. Besides, EEL could be a useful pharmacological utility for protection against cardiac dysmetabolism by inhibiting PDK-4.

Inhibition of pyruvate dehydrogenase kinase-4 by l-glutamine protects pregnant rats against fructose-induced obesity and hepatic lipid accumulation.

OBJECTIVE: Accumulation of lipids in non-adipose tissues particularly the liver is a feature of tissue insulin resistance. Hepatic glycogen depletion reflects counter glucoregulation in an insulin-resistant state and/or obesity. The effect of l-glutamine on fructose-induced increased hepatic lipid accumulation and depleted glycogen content, particularly in pregnancy, is not known. We therefore aimed at investigating the effect of glutamine on fructose-induced weight gain, hepatic lipids and glycogen contents in pregnant rats and also tested the hypothesis that hepatoprotective role of l-glutamine is through suppression of PDK-4. METHODS: Eleven-week-old pregnant Wistar rats were allotted into the Control, Glutamine, Fructose and Fructose plus Glutamine groups (6 rats/group). The groups received distilled water (vehicle, p.o.), 1 g/kg bwl-glutamine (p.o.), 10% Fructose (w/v) and 10% Fructose (w/v) plus 1 g/kg bwl-glutamine (p.o.) respectively, daily for 19 days. Biochemical analysis and histology of the liver were performed. RESULTS: Data showed that fructose intake caused insulin resistance, hyperglycemia, hyperlipidemia, increased body weight gain, visceral fat mass, hepatic mass, lactate production, uric acid production, lipid peroxidation and decreased pancreatic ß-cell function and hepatic glycogen synthesis. These alterations were accompanied by elevated pyruvate dehydrogenase kinase-4 (PDK-4). However, the fructose-induced dysmetabolism were improved by l-glutamine. CONCLUSION: Our results demonstrate that obesity and hepatic lipid accumulation induced by fructose in pregnant rats is accompanied by increased PDK-4. The findings also suggest that l-glutamine would protect against obesity and hepatic lipid accumulation by suppression of PDK-4.

Dipeptidyl peptidase-4 inhibition protects the liver of insulin-resistant female rats against triglyceride accumulation by suppressing uric acid.

Dipeptidyl peptidase-4 (DPP-4) inhibition has been shown to exert beneficial effects against insulin resistance (IR) and type 2 diabetes. Combined oral contraceptive (COC) treatment is associated with impaired glucose and lipid metabolism but the mechanisms are elusive. We therefore, hypothesized that DPP-4 inhibition ameliorates COC-induced glucose dysregulation and hepatic triglyceride (TG) accumulation through adenosine deaminase (ADA) /xanthine oxidase (XO) /uric acid-dependent pathway. Female Wistar rats received (po) vehicle and COC (1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel; po) with or without DPP-4 inhibitor (sitagliptin; 100 mg/kg; po) for 8 weeks (n = 6/group). Glucose dysmetabolism was assessed by elevated fasting blood glucose, impaired oral glucose tolerance test and homeostatic model assessment of IR. Treatment with COC led to increased plasma fasting glucose, triglyceride-glucose index, 1-h postload glucose response, insulin, free fatty acid, IR and impaired glucose tolerance. COC treatment also resulted in increased plasma and hepatic TG, TG/HDL-cholesterol ratio, malondialdehyde, uric acid (plasma; 25.2 ± 0.6 mg/dl; hepatic 128.9 ± 8.0 mg/100 mg tissue), lactate dehydrogenase, DPP-4, ADA and XO (plasma;10.5 ± 1.1 U/L; hepatic 21.2 ± 1.4 U/g protein) activities. Likewise, COC led to reduction in nitric oxide level. However, DPP-4 inhibition significantly ameliorated these alterations induced by COC treatment through suppression of uric acid (plasma; 15.1 ± 1.0 mg/dl, hepatic; 75.6 ± 5.0 mg/100 mg tissue), XO (plasma; 4.1 ± 0.9 U/L, hepatic; 8.7 ± 0.4 U/g protein), ADA and DPP-4 activities suggesting their involvement in glucose dysregulation and hepatic TG accumulation induced by COC treatment. Therefore, DPP-4 inhibition would impact positively on cardiometabolic disorders, at least in part, through XO, ADA and uric acid suppression.

Inhibition of adenosine deaminase and xanthine oxidase by valproic acid abates hepatic triglyceride accumulation independent of corticosteroids in female rats treated with estrogen-progestin.

Elevated circulating uric acid has been postulated to play an important pathophysiological role in estrogen-progestin combined oral contraceptive (COC)-induced hypertension and endothelial dysfunction. We hypothesized that disruption of glucoregulation and liver triglyceride (TG) accumulation induced by COC use would be abated by valproic acid (VPA) treatment through suppression of adenosine deaminase (ADA) and xanthine oxidase (XO) activities. Female Wistar rats aged 9-10 weeks were treated with a combination of estrogen-progestin COC steroids (1.0 µg ethinylestradiol and 5.0 µg levonorgestrel; p.o.) with or without VPA (100.0 mg/kg; p.o.) daily for 6 weeks. The result shows that the disrupted glucoregulation and associated elevated hepatic ADA activity, plasma and hepatic XO activity, uric acid (UA), TG/HDL-cholesterol, total cholesterol, and malondialdehyde induced by COC treatment were attenuated by VPA treatment. However, VPA did not have any effect on plasma aldosterone, corticosterone, ADA, circulating and hepatic free fatty acid. Our results demonstrate that suppression of plasma and hepatic XO activities, along with hepatic ADA activity and UA by VPA treatment, protects against disrupted glucoregulation and increased liver TG by COC independent of elevated corticosteroids. The findings imply that VPA would provide protection against the development of cardiometabolic disorder via inhibition of the ADA/XO/UA-mediated pathway.

High-fat diet reduces weight gain but increases other cardio-metabolic indices in offspring of normotensive and hypertensive rats.

This study investigated the effect of post-natal consumption of high-fat diet (HFD) on cardio-metabolic indices in male offspring of hypertensive female rats. There were neither significant differences in body weight gain either in pups from normotensive or hypertensive dams that received normal diet during the post-weaning periods (except at 7th and 9th weeks), nor in both pup groups that received HFD. However, both pup groups that received HFD had reduced body weight gain when compared to their counterparts that received normal diet. Post-weaning administration of HFD to pups of hypertensive and normotensive dams significantly increased their blood glucose, pressure and lipid profiles when compared to those weaned to normal diet. It was concluded that male offspring consumption of HFD diet elicits cardio-metabolic disturbance that slightly depended of maternal cardiovascular status but majorly depended on post-weaning weight gain, while that elicited by maternal hypertension is not related to post-weaning weight gain.