Increased Serum Total Cholesterol Research Articles

Impairment of bile acid metabolism by perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in human HepaRG hepatoma cells

Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are man-made chemicals that are used for the fabrication of many products with water- and dirt-repellent properties. The toxicological potential of both substances is currently under debate. In a recent Scientific Opinion, the European Food Safety Authority (EFSA) has identified increased serum total cholesterol levels in humans as one major critical effect being associated with exposure to PFOA or PFOS. In animal studies, both substances induced a decrease of serum cholesterol levels, and the underlying molecular mechanism(s) for these opposed effects are unclear so far. In the present study, we examined the impact of PFOA and PFOS on cholesterol homoeostasis in the human HepaRG cell line as a model for human hepatocytes. Cholesterol levels in HepaRG cells were not affected by PFOA or PFOS, but both substances strongly decreased synthesis of a number of bile acids. The expression of numerous genes whose products are involved in synthesis, metabolism and transport of cholesterol and bile acids was strongly affected by PFOA and PFOS at concentrations above 10 µM. Notably, both substances led to a strong decrease of CYP7A1, the key enzyme catalyzing the rate-limiting step in the synthesis of bile acids from cholesterol, both at the protein level and at the level of gene expression. Moreover, both substances led to a dilatation of bile canaliculi that are formed by differentiated HepaRG cells in vitro. Similar morphological changes are known to be induced by cholestatic agents in vivo. Thus, the strong impact of PFOA and PFOS on bile acid synthesis and bile canalicular morphology in our in vitro experiments may allow the notion that both substances have a cholestatic potential that is connected to the observed increased serum cholesterol levels in humans in epidemiological studies.

XKR6 rs7014968 SNP Increases Serum Total Cholesterol Levels and the Risk of Coronary Heart Disease and Ischemic Stroke.

The X Kell blood group complex subunit-related family member 6 (XKR6) gene single-nucleotide polymorphisms (SNPs) have been associated with serum lipid profiles and the risk of coronary heart disease (CHD) and ischemic stroke (IS) in several previous studies, but the association between the XKR6 rs7014968 SNP and serum lipid levels and the risk of CHD and IS has not been detected previously. This study aims to explore the association between the XKR6 rs7014968 SNP and serum lipid traits and the susceptibility to CHD and IS in the Guangxi Han Chinese population. Snapshot technology was used to determine the genotypes of the XKR6 rs7014968 SNP in 624 controls, 588 patients with CHD, and 544 patients with IS. The XKR6 rs7014968C allele carriers in the control group had higher serum total cholesterol (TC) levels than the C allele noncarriers (P = .025). The XKR6 rs7014968C allele carriers also had an increased risk of CHD and IS (P < .05-.01). Stratified analysis showed that the patients with the rs7014968C allele in the female, age >60 years, body mass index (BMI) >24 kg/m2, and hypertension subgroups had a higher risk of CHD than those in the subgroup counterparts. The patients with the rs7014968C allele in the male, BMI > 24 kg/m2, smoker, and hypertension subgroups also had a higher risk of IS than those in the subgroup counterparts. These results suggest that the XKR6 rs7014968 SNP is likely to increase the risk of CHD and IS by increasing serum TC levels in our study populations.

Effect of Stellaria media Tea on Lipid Profile in Rats.

Background In folk medicine, common chickweed (Stellaria media) has traditionally been applied for the treatment of hypercholesterolemia; however, there is no firm experimental proof to support the rationale of this practice. Therefore, we aimed to assess the efficacy and safety of Stellaria media) has traditionally been applied for the treatment of hypercholesterolemia; however, there is no firm experimental proof to support the rationale of this practice. Therefore, we aimed to assess the efficacy and safety of Materials and Methods. Adult male Wistar rats were divided into 3 groups. The (i) control group received standard laboratory chow, the (ii) hypercholesterolemic group received cholesterol-enriched diet, and the (iii) chickweed-treated hypercholesterolemic group received cholesterol-enriched diet and 100 mg/kg body weight Stellaria media) has traditionally been applied for the treatment of hypercholesterolemia; however, there is no firm experimental proof to support the rationale of this practice. Therefore, we aimed to assess the efficacy and safety of Results Cholesterol-enriched diet significantly increased serum total cholesterol, LDL- and HDL-cholesterol levels, but did not affect triacylglycerol concentrations. The addition of chickweed to the diet did not cause any significant change in serum lipid profile or body weight increase. Liver and kidney functions were unaltered and cardiac morphology and function were not changed due to Stellaria media) has traditionally been applied for the treatment of hypercholesterolemia; however, there is no firm experimental proof to support the rationale of this practice. Therefore, we aimed to assess the efficacy and safety of Conclusion Although chickweed does not seem to be toxic, our results do not support the rationale of its use in the treatment of hypercholesterolemia.

Effects of Long-Term Use of Depomedroxy Progesterone Acetate on Serum Lipids

Introduction: Long Acting Reversible Contraceptive (LARC) is one of the most popular method of family planning. The Aim of the study was to explore the effects of long-term use of Depomedroxyprogesterone acetate (DMPA) which is the most commonly used LARC, on serum lipid profile.&#x0D; Methods: This cross-sectional analytical study was carried out in the Department of Obstetrics and Gynaecology of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, during the period December 2015 to September 2016. A total 70 married women at the age range of 20-35 years attending, the family planning clinic of BSMMU were included in this study. Out of them 35 subjects who had been using DMPA for ³ two years uninterruptedly were considered as cases and another 35 subjects who did not use any hormonal contraceptives were labeled as control. In both the groups, age and BMI were matched. All the study subjects in both groups were apparently healthy. Fasting blood samples were collected from each subject for the estimation of Total Cholesterol (TC), Triglyceride (TG), High-density Lipoprotein Cholesterol (HDLC) and Low-density Lipoprotein Cholesterol (LDLC). The data were collected in a pre-designed data sheet and analyzed with student T-test for the statistical significance.&#x0D; Results: Serum TC and LDLC level in group-I (cases) were significantly higher compared to group-II (control) and the difference was statistically significant (p&lt;0.05). Serum High-density Lipoprotein Cholesterol (HDLC) level in group-I was lower than group-II which was also statistically significant (p=0.001). Serum Triglyceride level in group-I was higher than group- II, however the difference was not statistically significant (p=0.177).&#x0D; Conclusion: DMPA use for ³ two years increases serum TC and LDLC and decrease serum HDLC, which may increase the risk of atherosclerosis.&#x0D; Bangladesh J Obstet Gynaecol, 2019; Vol. 34(2): 106-111

Biological study on the impact of commonly used commercial fats and oil and threats of atherosclerosis

Poor health due to suboptimal nutrition influences on many diseases including diabetes mellitus, obesity, cardiovascular diseases (CVD), elevated cholesterol and blood pressure (BP). World health organization estimated that mortality rate and disease burden due to CVD was around 17.3 million. The prevalence rate of coronary artery diseases (CAD) is higher in Pakistan that is 30% of people age above 45 years. The objective of study involves evaluation of commonly used fats and oil to investigate its effect on lipid profile through in vivo studies. Hypercholesterolaemia was induced by feeding high cholesterol diet. Thirty Sprague dawdle rats were taken having five rats in each group. Margarine, butter, vanaspati ghee and olive oil were given with a specific dose 10 g/100 g feed given 6 weeks on hypercholesterolaemic rats. Maximum weight gain was observed in G2, G3, G4 fed; margarine, butter, vanaspati ghee respectively. And maximum reduction in weight was observed in G5 fed on olive oil. Feeding cholesterol diet showed elevated level of lipid profile in G1. Coincident giving various fats and oil along with high cholesterol diet caused a highly significant increase in serum total cholesterol, low density lipoprotein (LDL), triglycerides except G5. Maximum increase of cholesterol was observed in groups fed butter, margarine, vanaspati ghee were recorded as 177.6 mg/dL, 185.5 mg/dL, 180.7 mg/dL. Minimum reduction in cholesterol was recorded in olive oil group as 170.2 mg/dL. Results suggested that the addition of fats showed a negative influence on lipid profile in hypercholesterolaemic rats.

Sugar Kelp (Saccharina latissima) Inhibits Hepatic Inflammation and Fibrosis with Increased Metabolic Rates in a Mouse Model of Diet-induced Nonalcoholic Steatohepatitis (OR24-08-19)

ObjectivesWe investigated whether consumption of sugar kelp, an edible brown seaweed, can attenuate metabolic disturbances and nonalcoholic steatohepatitis (NASH) in a mouse model of NASH with evident liver fibrosis. MethodsMale C57BL/6 J mice were fed a low-fat control (LF; 6% fat by wt), a high-fat/high-sucrose/high-cholesterol control (HF; 34% fat, 34% sucrose, 2.0% cholesterol by wt), or a HF containing sugar kelp (HF-Kelp; 6.0% dried sugar kelp powder by wt) for 14 weeks. Blood chemistry as well as biochemical, molecular, and histological analyses were conducted in the liver and epididymal white adipose tissue (eWAT). Metabolic rates, energy expenditure, and physical activity of mice were determined using indirect calorimetry ResultsBody weight of mice fed HF-Kelp was significantly lower than that of HF group. Compared to LF, HF significantly increased serum total cholesterol and glucose, which were decreased by kelp. In the liver, HF-Kelp group showed decreases in weight, triglycerides, total cholesterol, and steatosis compared with HF-fed mice. Also, kelp decreased hepatic expression of a macrophage marker F4/80 and an M1 macrophage marker CD11c. Mice fed HF-Kelp also exhibited decreased liver fibrosis as evidenced by less expression of fibrogenic genes and collagen accumulation than those of HF group. In eWAT, HF-Kelp diet reduced weight and adipocyte size compared with HF control. While HF-Kelp diet increased mRNA abundance of peroxisome proliferator activated receptor γ, it decreased the expression of collagen type VI alpha 1 chain, F4/80, CD11c, and tumor necrosis factor α, in eWAT. Oxygen consumption, carbon dioxide production, energy expenditure, and physical activity were significantly higher in HF-Kelp group than HF. ConclusionsKelp consumption markedly prevented weight gain, fat accumulation, inflammation, and fibrosis in the liver and eWAT of mice with NASH. The health benefits of kelp were accompanied by increased metabolic rates, energy expenditure, and physical activity. Therefore, kelp may be consumed to prevent obesity-associated metabolic disturbances and NASH. Funding SourcesThis study was supported by USDA Hatch.

Association of Statin Use and High Serum Cholesterol Levels With Risk of Primary Open-Angle Glaucoma

The use of statins (hydroxymethylglutaryl coenzyme A inhibitors) has been associated with a lower risk of primary open-angle glaucoma (POAG); however, results have been conflicting, and little is known about the association between high cholesterol levels and POAG. To assess the association of elevated cholesterol levels and statin use with incident POAG. This study used data collected biennially from participants aged 40 years or older who were free of glaucoma and reported eye examinations, within 3 population-based cohorts: the Nurses' Health Study (N = 50 710; followed up from 2000 to 2014), the Nurses' Health Study 2 (N = 62 992; 1999-2015), and the Health Professionals Follow-up Study (N = 23 080; 2000-2014). Incident cases of POAG were confirmed by medical record review. The analyses were performed in January 2019. Biennially updated self-reported information on elevated cholesterol level status, serum cholesterol levels, and duration of statin use. Multivariable-adjusted relative risks (RRs) and 95% CIs were estimated using Cox proportional hazards regression models on pooled data, with stratification by cohort. Among the 136 782 participants in the 3 cohorts (113 702 women and 23 080 men), 886 incident cases of POAG were identified. Every 20-mg/dL increase in total serum cholesterol was associated with a 7% increase in risk of POAG (RR, 1.07 [95% CI, 1.02-1.11]; P = .004). Any self-reported history of elevated cholesterol was also associated with a higher risk of POAG (RR, 1.17 [95% CI, 1.00-1.37]). A history of any statin use was associated with a 15% lower risk of POAG (RR, 0.85 [95% CI, 0.73-0.99]). Use of statins for 5 or more years vs never use of statins was associated with a 21% lower risk of POAG (RR, 0.79 [95% CI, 0.65-0.97]; P = .02 for linear trend). The association between use of statins for 5 or more years vs never use of statins and risk of POAG was more inverse in those who were older (≥65 years: RR, 0.70 [95% CI, 0.56-0.87] vs <65 years: RR, 1.05 [95% CI, 0.68-1.63]; P = .01 for interaction). Among adults aged 40 years or older, higher serum cholesterol levels were associated with higher risk of POAG, while 5 or more years of statin use compared with never use of statins was associated with a lower risk of POAG.

Fried Sunflower Oil intake affects Bone Quality, in Growing Rats

The effect of consuming a diet containing sunflower oil, which was repeatedly used to fry potatoes, on bone mass and biomechanical competence in growing rats, was investigated. Male Wistar rats (21±1 days old) (n=34) were assigned at weaning to one of three diet groups for 8 weeks: those fed a control diet (C; n=10), a sunflower oil (SFO; n=12) diet or a SFO diet which was repeatedly heated (SFOx; n=12); both mixed with a commercial rat chow at weight ratio of 13% (w/w). Zoometrics, food intake, serum fatty acids composition and lipid profile, total skeleton bone mineral density (BMD), bone mineral content (BMC), and femur biomechanical competence were assessed. Animals fed SFOx diet had altered body growth and showed both increased serum total cholesterol (T-chol) and non-high-density lipoprotein cholesterol (non-HDL-chol). SFOx rats also showed marked differences in BMC, their femur and tibiae had the lowest structural and geometrical properties, but material properties were unchanged. This study showed that growing male rats consuming a SFOx diet adversely affected their body growth, and lipid metabolism. Additionally their BMC and bone biomechanical properties were also altered due to modifications in bone geometric design.

Protective Effects of Calcitriol Against Fructose‐induced Hyperglycaemia and Dyslipidaemia in Male Albino Wistar Rats

Hyperglycemia and lipidaemia have been found to produce adverse metabolic alterations in glucose and lipid metabolism. The study investigates the preventive role of calcitriol supplementation on fructose‐induced hyperglycaemia and dyslipidaemia in fructose‐drinking Albino Wistar rats. Twenty five male Albino rats were used. The rats were divided into 5 groups of 5 animals each. Group I: Control; received normal rat feed + distilled water, Group II: Received normal rat feed + 125 μg/kg of Calcitriol (CTR), Group III: Received normal rat feed + 10% fructose solution (FDR), Group IV: Received normal rat feed + 10% fructose solution (FDR) + 0.3 mg/kg of glibenclamide (GLIB). Group V: Received normal rat feed + 10% fructose solution (FDR) + 125 μg/kg of Calcitriol (CTR). For the induction of hyperglycaemia and lipidaemia rats were given 10% fructose solution as drinking water for eight weeks. The levels of fasting sugar and HbA1c were measured. Changes in body weights and lipid profile of rats were determined. CTR group exhibited no significant change in plasma glucose levels, HbA1c and body weights when compared to the control. In FDR group fasting sugar levels, glycated haemoglobin (HbA1c) and weights were found to be significantly increased compared group I. Glibenclamide administration in GLIB + FDR group effectively abolished the fructose‐induced hyperglycaemia and glycated haemoglobin in rats when compared to FDR group. In FDR + CTR group calcitriol supplementation successfully blocked and prevented the fructose‐induced increased in fasting sugar, HbA1c levels and weight in rats when compared with FDR group. CTR group exhibited no significant changes in lipid profile parameters compared control. FDR exhibited a significant increase in serum total cholesterol, when compared to control group. Similarly, fructose feeding resulted in a significant elevation in triglycerides levels in comparison to the control rats. FDR group rats had elevated levels of LDL‐C which was significant when compared with the control group. Although, high density lipoprotein cholesterol was increased in FDR group, the increased was not significant and the result was comparable to that of the control. In FDR + CTR group, oral calcitriol supplementation potentially prevented fructose in inducing alterations in serum lipid profiles when compared to FDR group. The result showed that calcitriol supplemention infructose‐drinking rats protects against hyperglycaemia and dyslipidaemia.Support or Funding InformationFunding is through the Tertiary Education Trust Fund, Nigeria. When an acceptance and invitation letter is forwarded to the Fund atleast 3 months before the conference timeThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

N-acetylcysteine and alpha-lipoic acid improve antioxidant defenses and decrease oxidative stress, inflammation and serum lipid levels in ovariectomized rats via estrogen-independent mechanisms

Sexual hormone deficiency has been associated with metabolic changes, oxidative stress and subclinical inflammation in postmenopausal women. Hormone replacement therapies are effective in many instances, even though some patients either do not respond or are not eligible. The aim of this study was to evaluate the impact of short- (15 days) versus long-term (60 days) sexual hormone depletion and whether antioxidant supplementation with N-acetylcysteine (NAC) and alpha-lipoic acid (LA) improves oxidative stress, metabolic, and inflammatory parameters in ovariectomized (OVX) rats. Short-term OVX rapidly depleted circulating estrogen, causing uterine atrophy and body weight gain without affecting oxidative damage, inflammatory and lipid metabolism markers. In contrast, long-term OVX augmented oxidative damage in serum and peripheral tissues as well as increased serum total cholesterol, TNF-α and IL6 levels. Triglycerides, glucose and HDL cholesterol were not altered. Long-term OVX-induced oxidative stress was associated with depletion of GSH and total non-enzymatic antioxidants as well as decreased activity of Glutathione Peroxidase (GPx) and Glutathione Reductase (GR), but not Superoxide Dismutase (SOD) and Catalase (CAT). NAC and LA supplementation prevented GSH and total non-enzymatic antioxidants depletion as well as restored GPx and GR activities, TNF-α, IL6 and cholesterol in OVX rats. NAC and LA effects appear to be independent on NRF2 activation and estrogen-like activity, since NAC/LA did not promote NRF2 activation and were not able to emulate estrogen effects in OVX rats and estrogen-receptor-positive cells. The herein presented data suggest that NAC and LA may improve some deleterious effects of sexual hormone depletion via estrogen-independent mechanisms.

Association between serum cholesterol levels and Alzheimer’s disease in China: a case-control study

To examine the association between blood cholesterol concentrations and Alzheimer’s disease (AD) in the Chinese elderly. A case-control study was implemented between November 2011 and November 2017. Elderly patients aged ≥ 55 years with (n = 117) and without AD (control participants; n = 117) were recruited from the Neurology Central Hospital of Tianjin, China. The associations between AD and blood parameters were assessed using multiple binary logistic regression analyses adjusted for multiple covariates. Higher serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and lower serum high-density lipoprotein cholesterol (HDL-C) levels associated with AD risk in the models adjusted for (1) age, sex and education; and (2) further adjusted for body mass index, smoking status, stroke, hypertension, type 2 diabetes mellitus and heart disease. Increased serum TC and LDL-C levels and lower HDL-C levels were independently associated with the risk of AD.

Study of Variation in Lipid Profile Parameters in Pre Menopausal and Post Menopausal Subjects

Menopause is a phase of woman's natural aging process and is marked by the cessation of ovarian function. The increased incidence of cardiovascular risk in the post-menopausal women may partly be due to hormonal changes leading to derangement of lipid metabolism. The present study is aimed to evaluate the variation in lipid profile in pre-and post-menopausal women. 50 Premenopausal & 50 Postmenopausal women were enrolled in the study after obtaining consent from each patient. Lipid profile was done & compared between both the groups. It was found in study that there is increase in serum Total Cholesterol (TC), Triglycerides (TG), LDL-cholesterol and VLDL-cholesterol level in post-menopausal women as compared to those in pre-menopausal women (p<0.001). HDL-cholesterol level was significantly decreased in post-menopausal women as compared to that in pre-menopausal women (p<0.001). Post-menopausal women are at increased risk of developing cardiovascular disease due to change in the lipid pattern and loss of cardioprotective effect of estrogen. Predicting the factors affecting the lipid profile in post-menopausal women, adopting strategies to control these mechanisms by modifying the relative risk factors during menopausal transition may improve the cardiovascular risk profile in these women.

Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food.

The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in food. Regarding PFOS and PFOA occurrence, the final data set available for dietary exposure assessment contained a total of 20,019 analytical results (PFOS n = 10,191 and PFOA n = 9,828). There were large differences between upper and lower bound exposure due to analytical methods with insufficient sensitivity. The CONTAM Panel considered the lower bound estimates to be closer to true exposure levels. Important contributors to the lower bound mean chronic exposure were ‘Fish and other seafood’, ‘Meat and meat products’ and ‘Eggs and egg products’, for PFOS, and ‘Milk and dairy products’, ‘Drinking water’ and ‘Fish and other seafood’ for PFOA. PFOS and PFOA are readily absorbed in the gastrointestinal tract, excreted in urine and faeces, and do not undergo metabolism. Estimated human half‐lives for PFOS and PFOA are about 5 years and 2–4 years, respectively. The derivation of a health‐based guidance value was based on human epidemiological studies. For PFOS, the increase in serum total cholesterol in adults, and the decrease in antibody response at vaccination in children were identified as the critical effects. For PFOA, the increase in serum total cholesterol was the critical effect. Also reduced birth weight (for both compounds) and increased prevalence of high serum levels of the liver enzyme alanine aminotransferase (ALT) (for PFOA) were considered. After benchmark modelling of serum levels of PFOS and PFOA, and estimating the corresponding daily intakes, the CONTAM Panel established a tolerable weekly intake (TWI) of 13 ng/kg body weight (bw) per week for PFOS and 6 ng/kg bw per week for PFOA. For both compounds, exposure of a considerable proportion of the population exceeds the proposed TWIs.

Hydro-Ethanolic Fruit Extract of Capsicum frutescens Reversed Triton-X-100–Induced Hyperlipidaemia in Rats

This study evaluates the anti-hyperlipidaemic and antioxidant activities of hydro-ethanolic fruits extract of Capsicum frutescens in hyperlipidemia rats. The secondary volatile metabolite constituents of the extract were identified using Gas chromatography. In vitro antioxidant activity of the extract (0.2–1.0 mg/mL) was investigated using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical, hydrogen peroxide (H2O2) and hydroxyl radical (OH.). In vivo antioxidant and anti-hyperlipidaemic properties of the extract were evaluated in triton X-100-induced hyperlipidaemic rats. Gas chromatogram indicates the presence of 13 compounds with tans β-ocimene being the major constituent. The extract scavenged DPPH, H2O2 and OH. radicals in concentrations dependent manner. C. frutescens reversed triton X-100-mediated increase in serum total cholesterol, triglycerides and low-density lipoprotein, and reduction in high-density lipoprotein. Triton X-100-mediated decrease in superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose 6-phospahte dehydrogenase were significantly reversed by the extract. The results indicate that C. frutescens has antioxidant and anti-hyperlipidaemic properties.

The effects of vitamin D supplementation on healthy and hypercholesterolemic rabbits on levels of OSI and paraoxonase

Abstract Objective Conflicting data are available in literature regarding the effects of vitamin D (VitD) supplementation diet on lipid panel. Therefore, we had the purpose to evaluate the effects of VitD supplementation on lipid panel by a controlled experimental study, and those of VitD supplementation on oxidative stress index (OSI) and paraoxonase-1 (PON1) values in healthy and hypercholesterolemic male rabbits. Methods Thirty New Zealand rabbits were randomly separated into control, VD, HC+VD and HC groups. Control and VD groups were fed with standard chow, whereas HC+VD and HC groups were fed with 0.5% cholesterol chow a period of 8 weeks. During this period, VD and HC+VD groups were orally administered with 300 IU/kg/day VitD. Results The increase in serum total cholesterol (TC) and OSI level of HC group were significant compared to those in HC+VD group. Decreases in serum HDL-cholesterol (HDL-C) and TC levels of VD group were significant within the groups. Conclusion Without any doubt it is important that applied VitD level should be in the ideal range for healthy living. However, it is also necessary to increase the serum HDL-C level (and hence PON1), which is decreases as a result of VitD supplementation. Therefore, we believe that during VitD supplementation, regular physical activity should be performed to increases serum HDL-C.

Boiled, sprouted, and raw cowpea-incorporated diets modulate high-fat diet-induced hypercholesterolemia in rats.

This study was carried out to investigate the effect of processed (boiled and sprouted) cowpea‐incorporated experimental diets on serum cholesterol and serum antioxidant capacity in high‐fat diet (HFD)‐fed Wistar rats. Seven weeks old male Wistar rats were fed 20% fat as a control (CD), for comparison with 20% fat‐enriched diets containing 20% whole raw cowpea diets (Bombay Raw Diet; BRD and MI35 Raw Diet; MRD), boiled cowpea diets (Bombay Boiled Diet; BBD and MI35 Boiled Diet; MBD) and sprouted cowpea diet (Bombay Sprouted Diet; BSD) for 6 weeks. The increase in serum total cholesterol as a result of high‐fat diet was significantly countered by boiled and raw cowpea‐incorporated diet‐fed rats. Increased serum non‐HDL‐C level caused by HFD was significantly (p < 0.05) countered by raw, boiled, and sprouted cowpeas, while HDL–C was increased by raw MI and boiled Bombay incorporated diets. Boiling has improved the hypocholesterolemic ability of Bombay cowpea and BBD has significantly (p < 0.05) modulated serum HDL‐C level and liver weight in rats. These findings were supported significantly high soluble fiber content in processed cowpea powder than that in raw cowpea powder. The decrease in serum antioxidant activity as a result of HFD was significantly countered by BRD. Processing has reduced the antioxidant activity in cowpeas and serum antioxidant activity in rats. Cecal lactobacilli population was significantly high in all cowpea diet‐fed groups compared to control. Modulated serum cholesterol level in cowpea diet‐fed rats was accompanied by dietary fiber composition, antioxidant activity in cowpeas and fecal weight, cecal weight and cecal lactobacilli population in rats compared to control. Both processed and raw cowpea‐incorporated diets have modulated HFD‐induced hypercholesterolemia by modulating serum antioxidative capacity, cholesterol metabolism, and cecal fermentation.

Mechanism mediating the protective effect of diacerein in ischemia-reperfusion-induced testicular injury in rats

AimsTorsion of the spermatic cord is a common urologic emergency and can lead to testicular necrosis and infertility. Diacerein (DIA) is interleukin-1b (IL-1b) blocker which has a protective role against myocardial ischemia-reperfusion, however, to-date this role has not been investigated in testicular ischemia- reperfusion (TIR). We aimed to investigate the role and mechanism of action of DIA in induced TIR. Main methodsDIA (50 mg/kg) was administered i.m (intramuscular) to rats in the presence or absence of TIR. Testicular weight changes and serum testosterone and total cholesterol levels were evaluated. In addition; the level of testicular tissue reduced glutathione (GSH), malondialdehyde (MDA), total nitrites (NOx) and the activity of superoxide dismutase (SOD) were measured. Histopathology and interleukin1b (IL-1b) immunoexpression were evaluated. Key findingsTIR manifested by significant decrease in testicular weight, serum testosterone and testicular tissue GSH levels and SOD activity as well as increase in serum total cholesterol, testicular MDA and NOx levels. TIR showed the histopathological changes of marked testicular damage with increase in IL-1b immunoexpression. DIA was able to normalize both testicular weight, serum testosterone and cholesterol levels with attenuation of oxidative stress parameters along with amelioration of histopathological changes and IL-1 b immunostaining induced by TIR. SignificanceDIA has a protective effect against TIR induced injury in rats mediated by its anti-inflammatory and anti-oxidant activities.

3. Study on lipid profile among adults with HBV and HCV related chronic liver diseases in Bangladesh-report from a tertiary centre

Background and Aims: Chronic Hepatitis B and C are the major causes of cirrhosis of Liver and Hepatocellular carcinoma in Bangladesh. Development of cirrhosis of liver result in derangement of metabolic functions. This study was conducted to find out the changes of lipid profile among adult with Chronic Viral Hepatitis B and C. Methods: This was cross sectional descriptive study in Medicine Inpatient Department of Rajshahi Medical College Hospital from June 2015 to july 2016. Total Number of Patients were 130. Among them 114 Chronic Hepatitis B and 16 patients chronic Hepatitis C. Age 18–65 years. Male 107, female 23. There were no comorbidities of these patients. Results: Among 130 Patients (116 Child's Pugh A & 14 Child's Pugh B). In HBV group Male 96, Female 18 and in HCV group Male 11, Female 05. Serum Total cholesterol, HDL, LDL and Serum Triglyceride were done in all patients in six monthly intervals. The results were reduction of Serum Total Cholesterol and HDL in 45 (39.47%) and increased Serum Triglyceride in 11 (09.65%) patients in HBV group. In HCV group increased Serum Total cholesterol and Serum Triglyceride in 07 (43.75%) and reduction of HDL in 03 (18.75%) patients. Conclusion: Developing countries like Bangladesh are likely to face an enormous burden of CLD and prevention and early diagnosis is essential to reduce economic loss and health system burden. Dyslipidemia is frequent in CLD & found with severity of the disease. Moreover, it may acts as a good predictor of CLD management. Till now, no needful studies are available in Bangladesh. Understanding the pattern of Dyslipidemia of hepatitis B & C related CLD in Bangladesh may enrich the clinician and may act as a baseline study for further research. The authors have none to declare.

Acute peat smoke inhalation sensitizes rats to the postprandial cardiometabolic effects of a high fat oral load

Wildland fire emissions cause adverse cardiopulmonary outcomes, yet controlled exposure studies to characterize health impacts of specific biomass sources have been complicated by the often latent effects of air pollution. The aim of this study was to determine if postprandial responses after a high fat challenge, long used clinically to predict cardiovascular risk, would unmask latent cardiometabolic responses in rats exposed to peat smoke, a key wildland fire air pollution source. Male Wistar Kyoto rats were exposed once (1 h) to filtered air (FA), or low (0.36 mg/m3 particulate matter) or high concentrations (3.30 mg/m3) of peat smoke, generated by burning peat from an Irish bog. Rats were then fasted overnight, and then administered an oral gavage of a HF suspension (60 kcal% from fat), mimicking a HF meal, 24 h post-exposure. In one cohort, cardiac and superior mesenteric artery function were assessed using high frequency ultrasound 2 h post gavage. In a second cohort, circulating lipids and hormones, pulmonary and systemic inflammatory markers, and circulating monocyte phenotype using flow cytometry were assessed before or 2 or 6 h after gavage. HF gavage alone elicited increases in circulating lipids characteristic of postprandial responses to a HF meal. Few effects were evident after peat exposure in un-gavaged rats. By contrast, exposure to low or high peat caused several changes relative to FA-exposed rats 2 and 6 h post HF gavage including increased heart isovolumic relaxation time, decreased serum glucose and insulin, increased CD11 b/c-expressing blood monocytes, increased serum total cholesterol, alpha-1 acid glycoprotein, and alpha-2 macroglobulin (p = 0.063), decreased serum corticosterone, and increased lung gamma-glutamyl transferase. In summary, these findings demonstrate that a HF challenge reveals effects of air pollution that may otherwise be imperceptible, particularly at low exposure levels, and suggest exposure may sensitize the body to mild inflammatory triggers.

Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine‐exposed female adult rat offspring

Clinical and animal studies have indicated that hypercholesterolemia and its associated diseases have intrauterine developmental origins. Our previous studies showed that prenatal caffeine exposure (PCE) led to fetal overexposure to maternal glucocorticoids (GCs) and increased serum total cholesterol levels in adult rat offspring. This study further confirms the intrauterine programming of PCE-induced hypercholesterolemia in female adult rat offspring. Pregnant Wistar rats were intragastrically administered caffeine (30, 60, and 120 mg/kg/d) from gestational day (GD)9 to 20. Female rat offspring were euthanized at GD20 and postnatal wk 12; several adult rat offspring were additionally subjected to ice-water swimming stimulation to induce chronic stress prior to death. The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9ac and H3K14ac) and expression of HMGCR. This GC-dependent cholesterol metabolism programming effect was sustained through adulthood, leading to the occurrence of hypercholesterolemia.-Xu, D., Luo, H. W., Hu, W., Hu, S. W., Yuan, C., Wang, G. H., Zhang, L., Yu, H., Magdalou, J., Chen, L. B., Wang, H. Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring.