Effects Of High Cholesterol Diet Research Articles

Berberine alleviates cholesterol and bile acid metabolism disorders induced by high cholesterol diet in mice

Berberine (BBR) is a traditional Chinese herb with broad antimicrobial activity. Gut microbiota plays an important role in the metabolism of bile acids and cholesterol. Our study investigated the effects of BBR on alleviating cholesterol and bile acid metabolism disorders induced by high cholesterol diet in mice. Adult male C57BL/6J mice fed with high cholesterol diet (HC) containing 1.25 % cholesterol (HC group) or fed with chow diet containing 0.02 % cholesterol (Chow group) served as controls. BBR50 and BBR100 group mice were fed with HC, and oral BBR daily at doses of 50 or 100 mg/kg respectively for 8 weeks. The results showed that BBR could reshape the homeostasis and composition of gut microbiota. The abundance of Clostridium genera was significantly inhibited by BBR, which resulted in a significant reduction of secondary bile acids within the enterohepatic circulation and a significant lower hydrophobic index of bile acids. The absorption of cholesterol in intestine, the deposition of cholesterol in liver and the excretion of cholesterol in biliary tract were significantly inhibited by BBR, which promoted the unsaturation of cholesterol in bile. These findings suggest the potential utility of BBR as a functional food to alleviate the negative effects of high cholesterol diet.

Effect of High Cholesterol Diet and α-Tocopherol Supplementation on Endoplasmic Retüculum Stress and Apoptosis in Hippocampus Tissue

Objective: Neurodegenerative diseases are life-threatening disorders that occur when cells in peripheral nervous system or brain lose function over time and ultimately die. Our study aimed to establish a high cholesterol fed rabbit model to investigate the status of endoplasmic reticulum (ER) stress, proteasome activity and apoptosis as well as the beneficial role of α-tocopherol on hippocampus. Methods: Hypercholesterolemic rabbit model was established by feeding on 2% cholesterol diet for 8 weeks, and α-tocopherol supplementation was applied with intramuscular injections. Alterations of Grp78, Grp94, Bax, Bcl-2 and BACE1 levels in hippocampus tissue were determined by western blotting, while proteasome activity was measured by fluorometric detection. Results: Cholesterol containing diet for 8 weeks increased well-known parameters of ER stress and apoptosis, together with no chance in proteasome activity. On the other hand, α-tocopherol supplementation in rabbits fed two percent cholesterol containing diet significantly down-regulated certain ER stress and apoptosis parameters along with an increase in proteasome activity. Conclusion: Our results underline a novel function of α-tocopherol in reducing cholesterol induced ER stress and apoptosis by increasing proteasome activity in the hippocampus.

Effects of Kombucha Tea on Side Effects of High Cholesterol Diet in Rabbits

Background: This research aimed to assess the effect of kombucha tea on reducing cholesterol (HCH) uptake and ameliorating biochemical and physiological side effects of high cholesterol diets. 
 Objectives: The aim of this research was evaluate the effectiveness of Kombucha tea in reducing cholesterol uptake as well as pathological and immunological side effects from high cholesterol diets in Rabbit. 
 Methods: A total of 32 rabbits were assigned into four groups: 1. Control, fed with standard pellets; 2. HCh+St, fed with high cholesterol diet; 3. HCh+Kom, fed with high cholesterol diet and orally received kombucha beverage; and 4. Kom+St, orally received kombucha beverage along with standard diet. Then, the blood Cholesterol (CHO), Triglycerides (TG), Low-density Lipoprotein (LDL), Malondialdehyde (MDA), ferritin, Creatine Phosphokinase (CPK), Interleukin-1 (IL-1), interleukin-6 (IL-6), and liver enzymes (alanine transaminase [ALT], and aspartate transaminase [ AST]), as well as liver histopathological features, were evaluated in all groups.
 Results: CHO and TG showed the highest level in the blood of the HCh+St group, whereas those gavaged with HCh+Kom displayed no change in TG and LDL. Conversely, the HCh+Kom group showed a significant increase in HDL when compared with HCh+St and Kom+St groups. MDA ferritin and CPK in the Kom+St group was significantly higher than the other groups, followed by HCh+Kom. No significant difference was observed in the values of IL-1 and IL-6 as well as ALT and AST between the experimental groups and the control group. Histopathological observations of the liver tissues revealed foam cells with an acidophilic appearance in the HCh+St group and hyperemia in the sinusoid of HCh+Kom and Kom+St groups. Degradation in pancreatic acini was observed in the HCh+St rabbits. 
 Conclusion: The data suggest that kombucha consumption is effective in preventing problems caused by high cholesterol diets.

Effect of nebivolol on altered skeletal and cardiac muscles induced by dyslipidemia in rats: impact on oxidative and inflammatory machineries

Aim High cholesterol diet is greatly linked to deleterious health consequences. In this work we tried to explore direct effects of high cholesterol diet on striated (skeletal and cardiac) muscle tissues and the mechanisms by which nebivolol could improve such harmful effects. Methods The study included 24 healthy adult male albino rats weighing 200-220 grams that were assigned into four groups: control group, control drug group, high cholesterol diet fed groups; one untreated the other was treated with nebivolol. Results In the cholesterol fed group, we found decreased blood HDL and NO with elevated total cholesterol, triglycerides, myoglobin, CK, LDH, ALP, in addition to elevated muscle tissue levels of HIF-1, NF-kB, MDA, and decreased expression of both eNOS, reduced GSH. Wire hanging test time was shorter in the high cholesterol group than control group rats, which was confirmed histologically by increased striated muscle fibre thickness and cytochrome area %. Nebivolol treatment ameliorated the effects of high cholesterol diet. Conclusion High cholesterol diet caused myopathic changes in rat striated muscle tissues mostly due to oxidative stress associated with enhanced NF-kB and HIF-1 expression. Nebivolol appears beneficial in the management of hypercholesterolaemia-induced striated muscle injury.

Effect of high cholesterol diet (HCHD) with oxidative stress modification on selected parameters of glomerular damage in rats

Effect of high cholesterol diet (HCHD) with oxidative stress modification on selected parameters of glomerular damage in rats

EARLY EFFECTS OF HIGH CHOLESTEROL DIET ON THE KIDNEY OF AN ANIMAL MODEL

Ponte Academic JournalMar 2018, Volume 74, Issue 3 EARLY EFFECTS OF HIGH CHOLESTEROL DIET ON THE KIDNEY OF AN ANIMAL MODELAuthor(s): ROSLINA ABDUL RAHIM ,Zenab B. Hamad Mohamed, Hamad Abdulsalam Hamad Alfarisi, Nor Zamzila Abdullah, Norra Harun, Naznin MuhammadJ. Ponte - Mar 2018 - Volume 74 - Issue 3 doi: 10.21506/j.ponte.2018.3.12 Abstract:BACKGROUND: Previous studies have proven that there exists a complex association between progressive kidney damage and hypercholesterolemia. Most of them focused on the impact of chronically high blood cholesterol levels on the kidney. Information on the early effects of hypercholesterolemia on the kidney is still lacking. The aim of this study is therefore to determine early effects of high cholesterol diet on the kidney in an animal model. METHODOLOGY: Ten female Sprague-Dawley rats were divided into two groups: the control group, fed with commercial rat pellet and the high cholesterol diet (HCD) group, fed with 12% cholesterol diet with 0.3% cholic acid. Biochemical analysis of the lipid profile and renal function were performed at completed 48 hours, 7 days, and 6 weeks of the experiment. The animals were sacrificed at 6 weeks and the kidneys were harvested for histological examination. RESULTS: The HCD group rats had significantly higher levels of serum total cholesterol (at 7 days and 6 weeks). The HDL-c and triglycerides levels were however lower at 6 weeks. The mean serum creatinine level of the HCD group were increased after 48 hours and 7 days compared to control group. Histological examination of the kidney tissue of the HCD group at 6 weeks revealed segmental mesangial hypercellularity and mesangial matrix expansion of the glomeruli. CONCLUSION: The 12% cholesterol diet induced dyslipidaemia in the animal model. It resulted in acute kidney injury based on the serum creatinine at 48 hours and also 7 days. Kidney tissues examined at 6 weeks revealed changes confined to mesangial cells of the renal glomeruli. Download full text:Check if you have access through your login credentials or your institution Username Password

Pro- and Anti-inflammatory Effects of High Cholesterol Diet on Aged Brain.

Both hypercholesterolemia and aging are related to cognitive decline or Alzheimer’s disease. However, their interactive influence on the neurodegenerative progress remains unclear. To address this issue, 6-month-old and 16-month-old female mice were fed a 3% cholesterol diet for 8 weeks, followed by hippocampus-related functional, pathological, biochemical and molecular analyses. The high cholesterol diet did not exacerbate age-dependent cognitive decline and hippocampal neuronal death, and even greatly mitigated decreases of synaptophysin and growth associated protein 43 expression in the hippocampus of aged mice. Compared with young controls, aged mice fed normal diet showed mild activation of hippocampal microglia with increased expression of CD68, a marker of the microglial M1 phenotype, and decreased expression of CD206, a marker of the microglial M2 phenotype. More interestingly, the high cholesterol diet not only improved NLRP3 inflammasome activation and IL-1β expression, but also increased levels of anti-inflammatory cytokines IL-4 and IL-6 in the hippocampus of old mice, suggesting playing pro- and anti-neuroinflammatory effects. In addition, the cholesterol rich diet resulted in a defect of the blood-brain barrier of aged hippocampus, as revealed by increased brain albumin content. These results have revealed both harmful and protective effects of high cholesterol diet on aged brain, which helps us to understand that hypercholesterolemia in the aged population is not associated with dementia and cognitive impairment.

Early Effects of High Cholesterol Diet on the Kidney of an Animal Model

Introduction: Previous studies have proven the existence of a complex association between progressive kidney damage and hypercholesterolemia. Most studies focused on the impact of chronic high blood cholesterol levels on the kidney. Information on the early effect of hypercholesterolemia on the kidney is still lacking. The aim of this study was therefore to determine early effect of high cholesterol diet on the kidney in an animal model. Materials and method: Ten female Sprague-Dawley rats were divided into two groups. The control group was fed with commercial rat pellet while the high cholesterol diet (HCD) group was fed with 12% cholesterol diet and 0.3% cholic acid. Biochemical analysis (lipid profile and renal function) was performed at 48 hours, 7 days and 6 weeks of the experiment. The animals were sacrificed at 6 weeks and the kidneys were harvested for histological examination. Results: The HCD group rats had significantly higher levels of serum total cholesterol (at 7 days and 6 weeks). The HDL-cholesterol and triglyceride levels were however lower at 6 weeks. The mean serum creatinine level of the HCD group were increased after 48 hours and 7 days compared to the control group. Histological examination of the kidney tissue of the HCD group at 6 weeks revealed segmental mesangial hypercellularity and mesangial matrix expansion of the glomeruli. Conclusion: The 12% cholesterol diet induced dyslipidaemia in the animal model. It resulted in acute kidney injury based on the serum creatinine at 48 hours and 7 days. Kidney tissues examined at 6 weeks revealed changes confined to mesangial cells of the renal glomeruli.

Effects of High-cholesterol Diet on Pravastatin Disposition in the Perfused Rat Liver.

Various nutrients modulate the expression of transporters; however, the effect of a high-cholesterol (HC) diet on the expression and function of hepatic transporters remains unclear. Here, we examined the effects of an HC diet on drug disposition via hepatic transporters, including organic anion-transporting polypeptide (Oatp), multidrug resistance-associated protein (Mrp), and bile salt export pump (Bsep). In situ perfused rat liver system was performed. The levels of pravastatin, which is taken up into hepatocytes by Oatp and excreted into bile by Mrp2, in the perfusate and in bile were measured using high-performance liquid chromatography. Pravastatin was rapidly eliminated in control and HC rats; however, the cumulative amounts of excreted in bile were significantly higher in HC rats than in controls possibly because of the enhanced bile flow in HC rats (0.93±0.05 μL/min in control, and 1.22±0.18 μL/min in HC). Real-time reverse-transcriptase polymerase chain reaction (PCR) and western blot assessment of the mRNA and protein levels of hepatic transporters showed a significant downregulation of the Oatp1a1 and Bsep proteins in HC rats, whereas no differences in Mrp2 and Mrp3 levels were observed between HC and control rats. The analysis of the localization of Mrp2 on the canalicular membrane by immunofluorescence showed no changes in HC rats, although Mrp2 was readily internalized from the canalicular membrane under specific conditions. The findings of the present study indicate that the HC diet affected the biliary excretion of pravastatin concomitant with increased bile flow, despite minimal effects on the expression of hepatic transporters. The HC diet could promote the biliary excretion of other drugs and metabolites that are substrates of Mrp2 and Bsep.

Dietary cholesterol promotes AOM-induced colorectal cancer through activating the NLRP3 inflammasome

Prolonged ingestion of a cholesterol-enriched diet induces chronic, auto-inflammatory responses resulting in significant health problems including colorectal cancer. Inflammasomes are thought to mediate intestinal homeostasis, and their dysregulation contributes to inflammatory bowel diseases and colitis-associated cancer (CAC). However, in vitro and in vivo information regarding the inflammation-inducing and tumor-promoting effect of cholesterol is lacking. Here we show that the cholesterol promoted colon carcinogenesis in azoxymethane (AOM)-treated mice through activating the NLRP3 inflammasome. High cholesterol diet (HCD) significantly increased inflammatory responses and tumor burden. Cholesterol crystals, detected in the colon of mice fed with HCD, also promoted NLRP3 inflammasome activation in macrophages, as indicated by elevated expression of cleaved caspase-1, formation of NLRP3–ASC–caspase-1 complex assembly, and higher IL-1β secretion. Importantly, cholesterol was found to inhibit the activity of AMPKα in macrophages, leading to a significant production of mitochondrial ROS, which in turn activated the NLRP3 inflammasome. Moreover, crystal uptake and cathepsin B accounted for cholesterol crystal-induced inactivation of AMPKα. Finally, HCD-induced increase in IL-1β secretion, macrophage infiltration and tumor burden was diminished by the deletion of NLRP3 in AOM-treated mice. Taken together, our findings demonstrate that the pro-inflammatory and cancer-promoting effects of HCD are mediated by the activation of NLRP3 inflammasome. Our study extended our knowledge on how dietary choices can influence processes involved in chronic inflammatory disorders and colorectal cancer.

High cholesterol diet leads to oxidant load and peroxidation in the rabbit kidney tissue.

The aim of this study was to investigate possible effects of high cholesterol diet on oxidant/antioxidant status in rabbit kidney tissues. Although a number of experimental animal models have suggested that hyperlipidemia is associated with progressive kidney failure data remain sparse on the role of dietary cholesterol intake on kidney disease. Twelve male New Zealand albino rabbits were randomly divided into two groups (control and cholesterol). Both groups were fed on a standard laboratory diet. Animals in the cholesterol group additionally received cholesterol (1 g/kg/day), orally. The study period was 12 weeks. Activities of catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), nitric oxide synthase (NOS), xanthine oxidase (XO), paraoxonase (PON), adenosine deaminase (ADA) enzymes and levels of malondialdehyde (MDA) and nitric oxide (NO) were measured in kidney tissue samples. Histological examination of the kidney tissue samples was also done. SOD, GSH-Px and XO enzyme activities were found to be decreased and NOS and PON activities increased significantly in cholesterol group compared to controls. As an indication of oxidation, MDA levels were found to be increased in cholesterol group. Histological examination revealed some derangements in the kidney tissue. High cholesterol diet creates oxidant load and causes peroxidation, which in turn, leads derangements in the rabbit kidney tissue (Tab. 2, Fig. 2, Ref. 69).

Vascular pathology of 20-month-old hypercholesterolemia mice in comparison to triple-transgenic and APPSwDI Alzheimer's disease mouse models.

Several studies have shown that elevated plasma cholesterol levels (i.e. hypercholesterolemia) serve as a risk factor for late-onset Alzheimer's disease (AD). However, it remains unclear how hypercholesterolemia may contribute to the onset and progression of AD pathology. In order to determine the role of hypercholesterolemia at various stages of AD, we evaluated the effects of high cholesterol diet (5% cholesterol) in wild-type (WT; C57BL6) and triple-transgenic AD (3xTg-AD; Psen1, APPSwe, tauB301L) mice at 7, 14, and 20 months. The transgenic APP-Swedish/Dutch/Iowa AD mouse model (APPSwDI) was used as a control since these animals are more pathologically-accelerated and are known to exhibit extensive plaque deposition and cerebral amyloid angiopathy. Here, we describe the effects of high cholesterol diet on: (1) cognitive function and stress, (2) AD-associated pathologies, (3) neuroinflammation, (4) blood–brain barrier disruption and ventricle size, and (5) vascular dysfunction. Our data show that high dietary cholesterol increases weight, slightly impairs cognitive function, promotes glial cell activation and complement-related pathways, enhances the infiltration of blood-derived proteins and alters vascular integrity, however, it does not induce AD-related pathologies. While normal-fed 3xTg-AD mice display a typical AD-like pathology in addition to severe cognitive impairment and neuroinflammation at 20 months of age, vascular alterations are less pronounced. No microbleedings were seen by MRI, however, the ventricle size was enlarged. Triple-transgenic AD mice, on the other hand, fed a high cholesterol diet do not survive past 14 months of age. Our data indicates that cholesterol does not markedly potentiate AD-related pathology, nor does it cause significant impairments in cognition. However, it appears that high cholesterol diet markedly increases stress-related plasma corticosterone levels as well as some vessel pathologies. Together, our findings represent the first demonstration of prolonged high cholesterol diet and the examination of its effects at various stages of cerebrovascular- and AD-related disease.

A comparative study on the effect of high cholesterol diet on the hippocampal CA1 area of adult and aged rats.

Dementia is one of the most important problems nowadays. Aging is associated with learning and memory impairments. Diet rich in cholesterol has been shown to be detrimental to cognitive performance. This work was carried out to compare the effect of high cholesterol diet on the hippocampus of adult and aged male albino rats. Twenty adult and twenty aged male rats were used in this study. According to age, the rats were randomly subdivided into balanced and high cholesterol diet fed groups. The diet was 15 g/rat/day for adult rats and 20 g/rat/day for aged rats for eight weeks. Serial coronal sections of hippocampus and blood samples were taken from each rat. For diet effect evaluation, Clinical, biochemical, histological, immunohistochemical, and morphometric assessments were done. In compare to a balanced diet fed rat, examination of Cornu Ammonis 1 (CA 1) area in the hippocampus of the high cholesterol diet adult rats showed degeneration, a significant decrease of the pyramidal cells, attenuation and/or thickening of small blood vessels, apparent increase of astrocytes and apparent decrease of Nissl's granules content. Moreover, the high cholesterol diet aged rats showed aggravation of senility changes of the hippocampus together with Alzheimer like pathological changes. In conclusion, the high cholesterol diet has a significant detrimental effect on the hippocampus and aging might pronounce this effect. So, we should direct our attention to limit cholesterol intake in our food to maintain a healthy life style for a successful aging.

Lack of P2Y13 in mice fed a high cholesterol diet results in decreased hepatic cholesterol content, biliary lipid secretion and reverse cholesterol transport

BackgroundThe protective effect of HDL is mostly attributed to their metabolic function in reverse cholesterol transport (RCT), a process whereby excess cellular cholesterol is taken up from peripheral cells, processed in HDL particles, and later delivered to the liver for further metabolism and biliary secretion. Mechanistically, the purinergic P2Y13 ADP-receptor is involved in hepatic HDL endocytosis (i.e., uptake of both HDL protein + lipid moieties), which is considered an important step of RCT. Accordingly, chow-fed P2Y13 knockout (P2Y13-/-) mice exhibit lower hepatic HDL uptake, which translates into a decrease of hepatic free cholesterol content and biliary cholesterol and phospholipid secretion.FindingsThe aim of this study was to determine the effect of high cholesterol diet (HCD) in P2Y13-/- mice, in order to mimic high dietary cholesterol intake, which is a major cause of dyslipidemia in humans. As previously reported with chow-diet, HCD did not affect plasma lipid levels in P2Y13-/- compared with control mice but decreased hepatic free and esterified cholesterol content (p < 0.05, P2Y13-/- versus control). Interestingly, biliary lipid secretion and macrophages-to-feces RCT were more dramatically impaired in P2Y13-/- mice fed a HCD than chow-diet. HCD did not enhance atherosclerosis in P2Y13-/- compared with control mice.ConclusionThis study demonstrates that high dietary cholesterol intake accentuated the metabolic phenotype of P2Y13-/- mice, with impaired hepatobiliary RCT. Although other animal models might be required to further evaluate the role of P2Y13 receptor in atherosclerosis, P2Y13 appears a promising target for therapeutic intervention aiming to stimulate RCT, particularly in individuals with lipid-rich diet.

Hypercholesterolemia and effects of high cholesterol diet in type IIa sodium-dependent phosphate co-transporter (Npt2a) deficient mice

The type IIa sodium-dependent phosphate co-transporter (Npt2a) is important to maintain renal inorganic phosphate (Pi) homeostasis and the plasma Pi levels. It has reported that disorder of Pi metabolism in kidney can be risk factors for cardiovascular disease as well as hypercholesterolemia. However, the relationship between Pi and cholesterol metabolism has not been clarified. The current study investigated the effects of Npt2a gene ablation that is known as hypophosphatemia model on cholesterol metabolism in mice. Npt2a deficient (Npt2a(-/-)) mice and wild type mice were fed diets with or without 2% cholesterol for 12 days. Plasma lipid and lipoprotein profile analysis revealed that plasma lipid levels (total, LDL and HDL cholesterol) were significantly higher in Npt2a(-/-) mice than wild type (WT) mice. Interestingly, high cholesterol diet markedly increased plasma levels of total, LDL and HDL cholesterol in WT mice, but not Npt2a(-/-) mice. On the other hand, there were no differences in body and liver weight, intake and hepatic lipid accumulation between WT and Npt2a(-/-) mice. These results suggest that ablation of Npt2a gene induces hypercholesterolemia and affects the ability to respond normally to dietary cholesterol.

Effect of High-Cholesterol Diet on Serum Leptin and Blood Lipid in Rabbits

Effect of High-Cholesterol Diet on Serum Leptin and Blood Lipid in Rabbits

High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats

To investigate the effects of high cholesterol diet on the development of osteoporosis and the underlying mechanisms in rats. Female Sprague-Dawley rats were randomly separated into 3 groups: (1) the high cholesterol fed rats were fed a high cholesterol diet containing 77% normal diet food, 3% cholesterol and 20% lard for 3 months; (2) ovariectomised (OVX) rats were bilaterally ovariectomised and fed a standard diet; and (3) the control rats were fed the standard diet. Bone mineral density (BMD) of the rats was measured using dual-energy X-ray absorptiometry. Serum levels of oestradiol (E2), osteocalcin (BGP) and carboxy-terminal collagen crosslinks (CTX) were measured using ELISA. Gene expression profile was determined with microarray. Mouse osteoblast cells (MC3T3-E1) were used for in vitro study. Proliferation, differentiation and oxidative stress of the osteoblasts were investigated using MTT, qRT-PCR and biochemical methods. In high cholesterol fed rats, the femur BMD and serum BGP level were significantly reduced, while the CTX level was significantly increased. DNA microarray analysis showed that 2290 genes were down-regulated and 992 genes were up-regulated in this group of rats. Of these genes, 1626 were also down-regulated and 1466 were up-regulated in OVX rats. In total, 370 genes were up-regulated in both groups, and 976 genes were down-regulated. Some of the down-regulated genes were found to code for proteins involved in the transforming growth factor beta (TGF-β)/bone morphogenic protein (BMP) and Wnt signaling pathways. The up-regulated genes were found to code for IL-6 and Ager with bone-resorption functions. Treatment of MC3T3-E1 cells with cholesterol (12.5-50 μg/mL) inhibited the cell proliferation and differentiation in vitro in a concentration-dependent manner. The treatment also concentration-dependently reduced the expression of BMP2 and Cbfa1, and increased the oxidative injury in MC3T3-E1 cells. The results suggest a close correlation between hypercholesterolaemia and osteoporosis. High cholesterol diet increases the risk of osteoporosis, possible via inhibiting the differentiation and proliferation of osteoblasts.

Oxygen free radicals as a mechanism of hypercholesterolemic atherosclerosis: Effects of probucol

We investigated the effects of high cholesterol diet in the presence and absence of probucol on the genesis of atherosclerosis, the blood lipid profile, aortic tissue lipid peroxidation product malondialdehyde (MDA), and aortic tissue chemiluminescence (CL) a marker for antioxidant reserve in rabbits. Five groups each of 10 rabbits were studied: group I, regular rabbit chow; group II, as I + cholesterol (0.5%); group III, as I + cholesterol (0.5%) and probucol (0.5 gm/kg/day); group IV, as I + cholesterol (1%), and group V, as I + cholesterol (1%) and probucol (0.5 gm/kg/day). Blood concentrations of triglyceride (TG), total cholesterol (TC), high density lipoproteincholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C) were measured at monthly intervals for 4 months. The aorta was removed at the end of the protocol for assessment of atherosclerotic changes (gross and microscopic), MDA concentration and CL. TC, LDL-C, LDL-C/HDL-C ratio increased in all the groups except group I, while VLDL-C increased in group II only. HDL-C decreased in groups III, IV and V but remained unchanged in groups I and II. There was a decrease in HDL-C and VLDL-C components and an increase in LDL-C components of total cholesterol in all the groups II, III, IV and V, the changes being greater in group IV than in group II. Probucol did not appreciably affect the changes in lipid profile except that it decreased HDL-C significantly. Aortic tissue MDA increased in groups II, IV and V to a similar extent. Aortic CL which was measured only in groups I, IV and V increased to similar extent in the latter two groups. Atherosclerotic changes were greater in group II than in group III but similar to that in groups IV and V. Histological changes were practically similar in groups II, III, IV and V. The increased levels of aortic MDA and CL, which were associated with development of atherosclerosis, suggest a role for oxygen free radicals in the pathogenesis of hypercholesterolemia-induced atherosclerosis. Protection afforded by probucol was associated with a decrease in aortic MDA in spite of hypercholesterolemia. Ineffectiveness of probucol in 1% cholesterolfed rabbits was associated with its inability to reduce MDA and increase antioxidant reserve. These findings further support for the hypothesis that oxygen free radicals are involved in the genesis and maintenance of hypercholesterolemic atherosclerosis.

Arginase Activities and Global Arginine Bioavailability in Wild-Type and ApoE-Deficient Mice: Responses to High Fat and High Cholesterol Diets

Increased catabolism of arginine by arginase is increasingly viewed as an important pathophysiological factor in cardiovascular disease, including atherosclerosis induced by high cholesterol diets. Whereas previous studies have focused primarily on effects of high cholesterol diets on arginase expression and arginine metabolism in specific blood vessels, there is no information regarding the impact of lipid diets on arginase activity or arginine bioavailability at a systemic level. We, therefore, evaluated the effects of high fat (HF) and high fat-high cholesterol (HC) diets on arginase activity in plasma and tissues and on global arginine bioavailability (defined as the ratio of plasma arginine to ornithine + citrulline) in apoE−/− and wild-type C57BL/6J mice. HC and HF diets led to reduced global arginine bioavailability in both strains. The HC diet resulted in significantly elevated plasma arginase in both strains, but the HF diet increased plasma arginase only in apoE−/− mice. Elevated plasma arginase activity correlated closely with increased alanine aminotransferase levels, indicating that liver damage was primarily responsible for elevated plasma arginase. The HC diet, which promotes atherogenesis, also resulted in increased arginase activity and expression of the type II isozyme of arginase in multiple tissues of apoE−/− mice only. These results raise the possibility that systemic changes in arginase activity and global arginine bioavailability may be contributing factors in the initiation and/or progression of cardiovascular disease.

Acute Effects of Hypercholesterolemic Diet on Erectile Responses in Rats

Objective: The aim of this study was to evaluate the acute effects of a high cholesterol diet (HCD) on erectile and endothelial functions in Sprague-Dawley rats. Materials and Methods: Sprague-Dawley rats were divided into 2 groups as control and HCD groups. The control group was fed on a normal diet and the hypercholesterolemia group was fed a 1% cholesterol-enriched diet daily for 2 weeks. Total cholesterol levels were measured at the end of 2 weeks in both groups. To examine the effect of HCD on erectile function, electric cavernous nerve stimulation (CNS) at 20 Hz with a pulse duration of 1 ms for 1 min at 5 V was performed. During CNS, we measured intracavernous pressure (ICP), mean arterial pressure (MAP), detumescence time and area under the curve (AUC). To evaluate the endothelial responses, acetylcholine (Ach) was applied cumulatively (1 nM to 1 µM) to thoracic aorta tissues contracted with 60 mM KCl. Results: In the HCD group total cholesterol levels were significantly higher than in the control group (148.1 ± 18.9 vs. 55.7 ± 8.1 mg/dl, p = 0.002). The detumescence time was significantly decreased after HCD compared to the control diet (19.3 ± 3.6 vs. 78.6 ± 12.8 s, p < 0.001). The decreases in the HCD group were also significant in terms of ICP (53.4 ± 4.5 vs. 35.6 ± 5.5 mm Hg; p < 0.05), ICP/MAP (55.9 ± 3.9 vs. 38.2 ± 5.2%; p < 0.05) and AUC (1,404 ± 197.1 vs. 2,250 ± 253.7, p < 0.05) values. There were no significant changes in maximum relaxation responses of the thoracic aorta to Ach. Conclusion: These results suggest that erectile functions were significantly damaged early in HCD rats. However, endothelial functions, evaluated in the thoracic aorta, were not affected simultaneously with erectile functions in rats fed a low concentration of HCD.