Rat Model Of Hypercholesterolemia Research Articles

Diosgenin regulates cholesterol metabolism in hypercholesterolemic rats by inhibiting NPC1L1 and enhancing ABCG5 and ABCG8

Hypercholesterolemia is a preventable risk factor for atherosclerosis and cardiovascular disease. However, the mechanisms of diosgenin (DG) that promote cholesterol homeostasis and alleviate hypercholesterolemia remain elusive. To investigate the effects and molecular mechanisms of the promotion of cholesterol metabolism by DG, a rat model of hypercholesterolemia was induced by providing a high-fat diet for 4 weeks. After 4 weeks, the rats were intragastrically administered high-dose DG (0.3 g/kg/d), low-dose DG (0.15 g/kg/d) or simvastatin (4 mg/kg/d) once a day for 8 weeks. The serum and hepatic cholesterol were tested, the mRNA and protein expression levels of Niemann-Pick C1-Like 1 (NPC1L1), liver X receptor-α (LXR-α) and the ATP-binding cassette G5/G8 (ABCG5/G8) transporters were measured. The results indicate that DG could reduce body weight, decrease the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, liver total cholesterol and free cholesterol levels compared to those in the controls. Simultaneously, liver tissue pathological morphology analyses revealed that DG could attenuate hepatic steatosis compared to that in the high-fat diet group. Further investigation demonstrated that DG significantly decreased the expression of NPC1L1 and LXR-α in the intestine and markedly increased the expression of ABCG5/G8 in the liver and intestine. Compared to the high-fat diet group, the rats in the DG-treated groups ameliorated hypercholesterolemia in a dose- and time-dependent manner. These data suggest that DG may not only inhibit intestinal cholesterol absorption by downregulating NPC1L1 but also enhance cholesterol excretion by increasing the expression of ABCG5/G8. DG could be a new candidate for the prevention of hypercholesterolemia.

Simvastatin does not adversely affect Achilles tendon properties in a diet induced hypercholesterolemia rat model

Simvastatin does not adversely affect Achilles tendon properties in a diet induced hypercholesterolemia rat model

Hypocholesterolemic Effects of Probiotic Mixture on Diet-Induced Hypercholesterolemic Rats.

Growing evidence has indicated that supplementation with probiotics improves lipid metabolism. We aimed to investigate the beneficial effects of a probiotics mixture (PM) of three strains belonging to the species Bifidobacterium (B. longum, B. lactis, and B. breve) and two strains belonging to the species Lactobacillus (L. reuteri and L. plantarum) on cholesterol-lowering efficacy in hypercholesterolemic rats. A hypercholesterolemic rat model was established by feeding a high-cholesterol diet for eight weeks. To test the effects of PM on hypercholesterolemia, hypercholesterolemic rats were assigned to four groups, which were treated daily with low (1.65 × 109 cfu/kg), medium (5.5 × 109 cfu/kg), or high (1.65 × 1010 cfu/kg) doses of probiotic mixture or simvastatin for eight weeks. Significant reductions of serum total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein (LDL)-cholesterol levels, but increases of high-density lipoprotein (HDL)-cholesterol were observed after supplementation of PM in hypercholesterolemic rats. In PM-supplemented hypercholesterolemic rats, hepatic tissue contents of TC and TG also significantly decreased. Notably, the histological evaluation of liver tissues demonstrated that PM dramatically decreased lipid accumulation. For their underlying mechanisms, we demonstrated that PM reduced expressions of cholesterol synthesis-related proteins such as sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) in the liver. Taken together, these findings suggest that PM has beneficial effects against hypercholesterolemia. Accordingly, our PM might be utilized as a novel therapeutic agent for the management of hypercholesterolemia.

Investigation of the Impact of Flaxseed (Linum Usitatissimum) on the Lower Extremity Ischemia/Reperfusion Injury in a Hypercholesterolemic Rat Model

Introduction: Ischemia is a condition in which the circulation fails to provide the oxygen and other metabolites required by the tissue, and to eliminate the waste products. Reperfusion is the recovery of blood flow and oxygen to a hypoxic tissue. The aim of this study is to investigate the effect of flaxseed (L. Usitatissimum) in a hyper cholesterolemic rat model of lower extremity ischemia-reperfusion injury.Material and method: 38 female Wistar rats weighing 200 to 250 grams were used in the study. The rats were assigned into 4 groups as follows: Group 1 (control, normal diet, n:8); Group 2 (40 mg/kg fed by body lignan complex, n:10), Group 3: (fed by 0.1% cholesterol containing diet, n:10), Group 4 (fed by 0.1% cholesterol containing diet+40 mg/kg body lignan complex, n:10). Ischemia was modeled by performing ligation of the left femoral artery using 6/0 prolene for two hours followed by two hours of perfusion and the blood flow was measured throughout the process in all groups by Doppler ultrasonography.Results: In Group 3, serum total cholesterol and triglyceride levels were higher compared to subjects in Group 1, Group 2 and Group 4 (p 0.05).Conclusion: The present study shows that flaxseed reduces the ischemia-reperfusion injury that occurs in femoral artery endothelium and gastrocnemius muscle following femoral artery occlusion-reperfusion in rats. The main findings in support of this conclusion include the significantly lower serum total cholesterol, LDL-cholesterol and triglyceride values in rats fed by flaxseed compared to hyper-cholesterolemic rats that were given flaxseed. In addition, assessment of the femoral artery endothelium and gastrocnemius muscle samples using the immunohistochemical method revealed significantly lower edema and neutrophil infiltration in rats fed by flaxseed.

In Vivo Antihypercholesterolemic Potential of Swietenia mahagoni Leaf Extract.

The present investigation aims to evaluate antihypercholesterolemic potential of Swietenia mahagoni leaf aqueous extract (MAE) in diet-induced hypercholesterolemic rat model. In the study, Wistar albino rats (170–220 g) were segregated into 5 groups; all the groups except normal control group were given high fat diet to induce hypercholesterolemia. After induction of cholesterolemia, normal control and positive control groups were treated with saline, statin group was treated with atorvastatin, and remaining two groups received MAE in two doses (250 and 500 mg kg−1 BW) for a treatment period of one month. After the treatment period, weight of rats was recorded and they were anesthetized and decapitated. Blood samples were taken and triglycerides, total cholesterol, LDL-C, HDL-C, malondialdehyde (MDA), and urea were determined. Liver and kidney were taken for the estimation of lipid peroxides. The positive control group showed higher values of triglycerides (109 ± 5.1 mg/dL), total cholesterol (134 ± 4.6 mg/dL), LDL-C (44 ± 1.2 mg/dL), MDA, and bile acid content when compared to a normal control group (triglycerides (89 ± 3.2 mg/dL), total cholesterol (72 ± 3.4 mg/dL), and LDL-C (28 ± 1.2 mg/dL)). Treatment with MAE decreased the cholesterol levels, HDL-C, ALT, AST, and bilirubin levels and the effect was dependent on the dose. The results of this study indicated that MAE possesses hypolipidemic potential and thus could be useful in the treatment of hypercholesterolemic condition.

Alligator pepper/Grain of Paradise (Aframomum melegueta) modulates Angiotensin-I converting enzyme activity, lipid profile and oxidative imbalances in a rat model of hypercholesterolemia

Alligator pepper [Aframomum melegueta Roscoe K. (Zingiberaceae)] seeds have been reportedly used in folkloric medicine in the management of hypercholesterolemia and hypertension with limited scientific basis for their action. This study was conducted to characterize the amino acids in Alligator pepper seeds (APS), assess their effects on lipid profile and enzyme linked to blood pressure regulation in hypercholesterolemic rat (rats fed 2% cholesterol diet) model. Free and total amino acids of APS were extracted and their various constituents were analyzed using the amino acid analyzer and ultra-performance liquid chromatography. The effect of dietary inclusion of APS (2–4%) on the lipid profile, angiotensin I-enzyme (ACE) activity and antioxidant status in hypercholesterolemic rats (HCR) for 30days was assessed. The results suggest that APS may modulate blood lipid profile, ameliorate blood pressure, attenuate hepatotoxicity and exert antihypercholesterolemic effect. γ − amino butyric acid (GABA), tyrosine, phenylalanine and tryptophan that were subsequently detected in APS. The observed salutary effects of APS may be attributed to the synergistic or/and additive actions of the amino acids present with other antioxidant phytoconstituents. These findings may therefore provide pharmacological basis for APS use in the treatment of hypercholesterolemia, hyperlipidemia and hypertension.

Effect of simvastatin on rat supraspinatus tendon mechanical and histological properties in a diet-induced hypercholesterolemia model.

Hypercholesterolemia is a common condition and is a risk factor for tendon rupture, specifically in the supraspinatus tendon. In the clinic, statins are commonly prescribed to lower cholesterol, but little information is available examining the effect of statin treatment on the musculoskeletal system. Therefore, the objective of this study was to determine the biomechanical and histological effects of statin treatment in a diet-induced hypercholesterolemia model. We hypothesized that hypercholesterolemic rats treated with statins would have improved tendon biomechanical and histological properties compared to hypercholesterolemic rats not receiving daily statin treatment. Thirty adult male Sprague-Dawley rats ate either high-cholesterol (HC) diet (n = 20) or normal chow (CTL, n = 10). After 6 months, a subset of HC rats began daily oral simvastatin dosing (HC+S) at 20 mg/kg. All rats were sacrificed after a total of 9 months (3 months of statin treatment) and evaluated for histology and mechanics. For mechanics, at the insertion region, HC+S group had increased tendon cross-sectional area decreased and modulus. No differences were noted in mechanical properties at the midsubstance. For histology, no differences were noted in the insertion region. In the midsubstance region, HC+S group had more spindle shaped cells. Our results suggest that 3 months of simvastatin treatment in a diet-induced hypercholesterolemia rat model alters some tendon mechanical and histological properties, although a strong conclusion in support of improved parameters cannot be drawn. Therefore, we conclude that simvastatin treatment does not negatively affect tendon properties. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2009-2015, 2016.

Acute and Chronic Pretreatment With Atenolol Attenuates Intestinal Ischemia and Reperfusion Injury in Hypercholesterolemic Rats.

To evaluate the protective effects of preinjury atenolol (acute v chronic) on apoptosis, contractility, oxidative stress, and inflammatory markers in hypercholesterolemic rats undergoing intestinal ischemia-reperfusion (I/R) injury. Prospective, experimental animal study. University laboratory. Male Wistar rats (n = 32). Rats were divided into the following 4 groups: 1 group was fed a normal diet (ND) (group ND+NoAT [no atenolol]), and the other 3 groups were fed a high-cholesterol diet (HCD)-group HCD+NoAT, group HCD+ChAT (chronic atenolol, 3 mg/kg/day for 8 weeks), and group HCD+AcAT (acute atenolol, 1.5 mg/kg, given 5 minutes before intestinal clamping). All rats underwent I/R injury. The superior mesenteric artery was clamped for 60 minutes, then opened for 120 minutes (reperfusion). Apoptotic cells and stimulated contractions of ileal segments were examined. Tissue markers of intestinal I/R injury were examined. Intestinal malondialdehyde, superoxide dismutase, and nitrate/nitrite levels were measured. The chronic atenolol group had fewer apoptotic cells and higher superoxide dismutase activity compared with the other groups. Intestinal contraction was higher in both atenolol pretreatment groups compared with the NoAT groups. Chronic and acute atenolol resulted in lower ileal levels of malondialdehyde and immunolabeling-positive cells (intestinal inducible nitric oxide synthase, endothelial nitric oxide synthase, interleukin-1, and interleukin-8) after I/R injury compared with the no atenolol groups. Both chronic and acute pre-I/R injury treatment with atenolol attenuated I/R injury in this hypercholesterolemic rat model. These findings should encourage future studies of atenolol in hypercholesterolemic patients undergoing procedures with a high risk of intestinal ischemia.

Antiatherogenic Effect of Camellia japonica Fruit Extract in High Fat Diet‐Fed Rats

Hypercholesterolemia is a well-known etiological factor for cardiovascular disease and a common symptom of most types of metabolic disorders. Camellia japonica is a traditional garden plant, and its flower and seed have been used as a base oil of traditional cosmetics in East Asia. The present study was carried out to evaluate the effect of C. japonica fruit extracts (CJF) in a high fat diet- (HFD-) induced hypercholesterolemic rat model. CJF was administered orally at three different doses: 100, 400, and 800 mg·kg−1·day−1 (CJF 100, 400, and 800, resp.). Our results showed that CJF possessed strong cholesterol-lowering potency as indicated by the decrease in serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL), accompanied by an increase in serum high-density lipoprotein (HDL). Furthermore, CJF reduced serum lipid peroxidation by suppressing the formation of thiobarbituric acid reactive substance. In addition, oil red O (ORO) staining of rat arteries showed decreased lipid-positive staining in the CJF-treated groups compared to the control HFD group. Taken together, these results suggest that CJF could be a potent herbal therapeutic option and source of a functional food for the prevention and treatment of atherosclerosis and other diseases associated with hypercholesterolemia.

African Nutmeg (Monodora Myristica) Lowers Cholesterol and Modulates Lipid Peroxidation in Experimentally Induced Hypercholesterolemic Male Wistar Rats

To evaluate the cholesterol lowering potential and protective ability of aqueous extract of Monodora myristica experimental hypercholesterolemic rats, a short-term study was conducted. Hypercholesterolemia was induced by administering cholesterol orally at a dose of 40 mg/kg/0.3 ml. Plant extracts 100 or 200 mg/kg body weight and Questran 0.26 g/kg were administered five times a week for eight weeks for amelioration. Hypolipidemic effects were evaluated by measuring total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) in the serum, while the protective ability was measured by the extent of lipid peroxidation (LPO) as well as enzymatic and non-enzymatic antioxidants levels in post mitochondrial fractions (PMF) of the hepatic and cardiac homogenates. Serum aminotransferases activities were also monitored. Results obtained shows that treatment with M. myristica elicited a significant reduction in serum TC, TG and LDL-C levels while there was concomitant increase in HDL-C of hypercholesterolemic rats. Elevations in serum aminotransferases activities and LPO level were reversed and a significant amelioration was noticed in enzymatic and non-enzymatic antioxidants status in the liver and heart of hypercholesterolemic rats. This study suggests that M. myristica possess cholesterol lowering potentials and protective ability in experimental hypercholesterolemia rat model.

Amelioration of oxidative and inflammatory status in hearts of cholesterol-fed rats supplemented with oils or oil-products with extra virgin olive oil components.

The contribution of extra virgin olive oil (EVOO) macro- and micro-constituents in heart oxidative and inflammatory status in a hypercholesterolemic rat model was evaluated. Fatty acid profile as well as α-tocopherol, sterol, and squalene content was identified directly in rat hearts to distinguish the effect of individual components or to enlighten the potential synergisms. Oils and oil-products with discernible lipid and polar phenolic content were used. Wistar rats were fed a high-cholesterol diet solely, or supplemented with one of the following oils, i.e., EVOO, sunflower oil (SO), and high-oleic sunflower oil (HOSO) or oil-products, i.e., phenolics-deprived EVOO [EVOO(-)], SO enriched with the EVOO phenolics [SO(+)], and HOSO enriched with the EVOO phenolics [HOSO(+)]. Dietary treatment lasted 9 weeks; at the end of the intervention blood and heart samples were collected. High-cholesterol-diet-induced dyslipidemia was shown by increase in serum total cholesterol, low-density lipoprotein cholesterol, and triacylglycerols. Dyslipidemia resulted in increased malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) levels, while glutathione and interleukin 6 levels remained unaffected in all intervention groups. Augmentation observed in MDA and TNF-α was attenuated in EVOO, SO(+), and HOSO(+) groups. Heart squalene and cholesterol content remained unaffected among all groups studied. Heart α-tocopherol was determined by oil α-tocopherol content. Variations were observed for heart β-sitosterol, while heterogeneity was reported with respect to heart fatty acid profile in all intervention groups. Overall, we suggest that the EVOO-polar phenolic compounds decreased MDA and TNF-α in hearts of cholesterol-fed rats.

ANTI ATHEROSCLEROTIC EFFECT OF ETHANOLIC STEM EXTRACT OF CISSUS QUADRANGULARIS LINN

Atherosclerosis and the subsequent complications cause many deaths world wide. Though many medications like statins and surgical procedures are available to tackle this problem, none of them is hazard free. In the present study the ethanolic extract of the plant Cissus quadrangularis, traditionally used for many ailments including elevated blood cholesterol is evaluated scientifically on rat model of hypercholesterolemia for its antiatherosclerotic effect. The study done in atherogenic diet induced hypercholesterolemic rats, in comparison with the standard drug Atorvastatin revealed the dose dependent effect of the extract to increase the antioxidant levels like SOD and catalase and to decrease the damage due to lipid peroxidation. Moreover, the plant exhibited significant anticoagulant and membrane stabilizing effect apart from decreasing LDL and VLDL and increasing HDL level, all relevant in the prevention of complications due to atherosclerosis. Histopathological examination of liver and coronary artery of the treated rats also suggested the protective effect of the extract in atherosclerosis.

Homocysteine has anti-inflammatory properties in a hypercholesterolemic rat model in vivo

Inflammation is a hallmark in many neurodegenerative diseases like Alzheimer's disease or vascular dementia. Cholesterol and homocysteine are both vascular risk factors which have been associated with dementia, inflammation and blood–brain barrier dysfunction. In previous studies we found that hypercholesterolemia but not hyperhomocysteinemia induced inflammation in rats in vivo. The aim of the present study was to investigate the effect of a combined treatment of Sprague Dawley rats with cholesterol and homocysteine for 5months on spatial learning and memory, blood–brain barrier integrity and inflammation. Cholesterol treated rats showed severe learning deficits, while rats treated with cholesterol and homocysteine (Mix) counteracted the cholesterol-induced inflammation and partly the cortical blood–brain barrier disruptions, although cognition was still impaired. To study the potential protective effect of homocysteine, inflammation was induced in organotypic rat brain cortex slices and primary microglial cells by treatment with different inflammatory stimuli (e.g. lipopolysaccharide or tissue plasminogen activator). Tissue plasminogen activator-induced inflammation was counteracted by homocysteine. In conclusion, our data demonstrate that homocysteine significantly ameliorates cholesterol-induced inflammation and blood–brain barrier disruption but not the memory impairment, possibly involving a tissue plasminogen activator-related mechanism.

Expression of Lectin like Oxidized Low Density Lipoprotein Receptor-1 in the Spontaneous Hypertensive Rat with High Cholesterol Diet

❙ABSTRACT❙ Background: Lectin-like, oxidized, low-density lipoprotein receptorreceptors (LOX-1) recognizes recognize vascular oxidized low-density lipoprotein (LDL), which may play an important role in the pathogenesis of atherosclerosis. We investigated the expressions expression of LOX-1 and redox-regulating thyoredoxinthioredoxin systems in a hypertension and hypercholesterolemia rat model. Methods: Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rat (WKY) rats were fed with a normal cholesterol diet (NC) and a high cholesterol diet (HC) for 4 weeks. Plasma LDL cholesterol levels and blood pressure were measured at 1 and 4 weeks. Histological changes of atherosclerosis in the vessel was evaluated by hematoxylin and eosin staining and immunocytochemistry. The expressions expression of LOX-1 and thyoredoixnthioredoxin were measured by Western western blot analysis. Results: In the SHR groupsgroup, blood pressure after 4 weeks was significantly higher than initial levels. LDL-cholesterol levels in the SHR-HC group were increased at 4 weeks (15.3 ± 2.6 mg/dL vs. 20.2 ± 2.6 mg/dL, p < 0.01) compared with the SHR-NC group. In oxyblot analysis, the degree of oxidative stress of in the SHR-HC group was significantly higher than in the SHR-NC group (p < 0.05). The expressions expression of LOX-1 and Trx were was significantly increased in the SHR-HC group compared with the SHR-NC group (p < 0.05) on western blot analysis. Focal overexpressions overexpression of LOX-1 were was observed at the intima layer of the thoracic aorta, and was which wereonly observed in the SHR-HC group. Conclusions: The expressions expression of LOX-1 and oxidative stress were was significantly increased in the “hypertension with hypercholesterol” rat model. These findings suggested suggest that LOX-1 and redox systems may play a certain role in development and progression of atherosclerosis. (J Korean Soc Hypertens 2011;17(2):57-64)

Aspirin restores normal baroreflex function in hypercholesterolemic rats by its antioxidative action

Besides its well-known effects on platelet aggregation, aspirin has been suggested to be an antioxidant and is also known to improve the lipid profile. In the present study we tested the hypothesis that aspirin by its antioxidant effect, improves haemodynamic profile and baroreflex sensitivity in rat model of hypercholesterolemia. Hypercholesterolemia was induced in Wistar rats by feeding 1% cholesterol rich diet for 10 weeks. Lipid profile, lipid peroxidation and reduced glutathione were estimated in serum. Haemodynamic changes and baroreflex were measured in anaesthetized rats. Hypercholesterolemic rats showed significant increase in total cholesterol, low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C) and atherogenic index and significant decrease in high-density lipoprotein-cholesterol (HDL-C). Significant rise in blood pressure, heart rate and attenuation of baroreflex sensitivity were also found in hypercholesterolemic rat. Aspirin in the dose of 100 mg/kg showed significant decrease in total cholesterol, LDL-C, VLDL-C and atherogenic index and significant increase in HDL-C. Aspirin treatment prevented the rise in blood pressure, heart rate and significantly improved baroreflex sensitivity in hypercholesterolemic rats. Hypercholesterolemic rats showed free radical generation, evident by a significant increase in serum lipid peroxidation and significant reduction in serum reduced glutathione content. Aspirin treatment significantly decreased lipid peroxidation and significantly increased reduced glutathione content. We have demonstrated that aspirin improves baroreflex response and prevents the rise in blood pressure and heart rate possibly by reducing sympathetic activity due to its antioxidant effect in experimentally induced hypercholesterolemic rats.

Downregulation of angiogenic factors and their downstream target molecules affects the deterioration of erectile function in a rat model of hypercholesterolemia

Objectives To evaluate how the expression of angiogenic factors and their downstream target molecules, which are potentially involved in penile homeostasis, is related to erectile dysfunction in a rat model of hypercholesterolemia. Methods Fifty-six 2-month-old male Sprague-Dawley rats were included in this study. The control animals (n = 28) were fed a normal diet, and the experimental animals (n = 28) were fed a diet containing 4% cholesterol and 1% cholic acid for 3 months. Erectile function was evaluated by cavernous nerve electrical stimulation, and cavernous tissue was harvested for histologic examination (n = 12, respectively). Cavernous tissue specimens from the remaining rats were used for reverse transcriptase–polymerase chain reaction (RT-PCR), Western blot, or cyclic guanosine monophosphate (cGMP) measurement. Results The ratio of maximal intracavernous pressure to mean arterial pressure was significantly lower in the hypercholesterolemic rats than in the controls ( P <0.01). Analysis by RT-PCR and Western blot showed significantly lower gene expression of vascular endothelial growth factor (VEGF), angiopoietin-1, and angiopoietin-2 and significantly lower protein expression of VEGF, angiopoietin-1, angiopoietin-2, the ratio of phospho-Akt to Akt, and phospho-endothelial nitric oxide synthase (eNOS) to eNOS in hypercholesterolemic rats than in controls. Cavernous tissue cGMP concentrations and endothelial area were also significantly lower in hypercholesterolemic rats than in controls ( P <0.01). Conclusions Downregulation of the expression of the angiogenic factors and their downstream signal molecules, and decreased endothelial content in the corpus cavernosum of hypercholesterolemic rats might play important roles in the deterioration of erectile function.

Combined Angiopoietin-1 and vascular endothelial growth factor gene transfer restores cavernous angiogenesis and erectile function in a rat model of hypercholesterolemia

Hypercholesterolemia-related endothelial cell dysfunction and decreased endothelium-derived nitric oxide formation may account for impaired angiogenesis and subsequent erectile dysfunction. Angiopoietin-1 (Ang1) is a critical angiogenic factor for vascular maturation and enhances vascular endothelial growth factor (VEGF)-induced angiogenesis in a complementary manner. We hypothesized that combined adenovirus-delivered human Ang1 (ad-Ang1) and VEGF165 (ad-VEGF165) gene transfer might promote angiogenesis cooperatively in a rat model of hypercholesterolemic erectile dysfunction and result in a recovery of erectile function. Ad-Ang1 and ad-VEGF165 were injected either alone or in combination into the corpus cavernosum of the penis. Combined gene transfer of both ad-Ang1 and ad-VEGF165 significantly increased cavernous angiogenesis, eNOS phosphorylation, and cGMP expression compared with that in the groups treated with either therapy alone. Erectile function, as evaluated by electrical stimulation of the cavernous nerve 2 and 8 weeks after treatment, was completely restored in the combined treatment group, whereas intracavernous injection of either ad-Ang1 or ad-VEGF165 alone elicited partial improvement. The results indicate that combined application of angiogenic factors may enhance cavernous angiogenesis cooperatively by reinforcing the endothelium both structurally and functionally, which results in an additive effect on erectile function in hypercholesterolemic rats.

The Protective Role of Chinese Prescription Kangen-karyu Extract on Diet-Induced Hypercholesterolemia in Rats

This study was carried out to investigate the protective potential of Chinese prescription Kangen-karyu, comprising six crude drugs, on coronary heart disease which is the principal cause of morbidity and mortality worldwide. The diet-induced hypercholesterolemic rat model, which shows an elevation in low density lipoprotein (LDL) cholesterol and atherosclerosis, was employed. The control rats fed a diet of 1% cholesterol and 0.5% cholic acid showed the highest cholesterol levels in serum and feces relative to those fed a normal diet, however, the rats administered Kangen-karyu extract showed reductions in these levels without changes in liver cholesterol, indicating that the reduction of serum total cholesterol by Kangen-karyu extract probably arises from an increase in cholesterol excretion. Furthermore, the administration of Kangen-karyu extract significantly prevented the elevation of serum aspartate aminotransferase and alanine aminotransferase, known as marker enzymes of liver damage. The elevated serum levels of LDL cholesterol were lowered, however, the high density lipoprotein cholesterol level was significantly elevated by Kangen-karyu extract and these were dose-dependent decreases in the atherogenic index to 15.2, 8.8 and 7.5 at oral doses of 50, 100 and 200 mg from the 19.4 control value, respectively. In addition, Kangen-karyu extract inhibited LDL oxidation in a dose-dependent manner, and the elevated level of thiobarbituric acid-reactive substances in control rats showed a decline by the administration of Kangen-karyu extract. The present study suggests that Kangen-karyu could play a protective role against hypercholesterolemia through the regulation of cholesterol levels and inhibition of lipid peroxidation.

Effects of soy components on blood and liver lipids in rats fed high-cholesterol diets

To assess the effects of soy protein, isoflavone, and saponin on liver and blood lipid in rats that consumed high-cholesterol diets. High-cholesterol diets (1%) with or without soy material were fed to 6-wk-old male Sprague-Dawley rats for 8 wk. Blood lipids, liver lipids, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) levels were measured. The in vitro bile acid-binding ability of soy materials was analyzed. The results of in vitro studies showed that soy protein isolate had a significantly higher bile acid-binding ability (8.4+/-0.8%) than soy saponin (3.1+/-0.7%) and isoflavone (1.3+/-0.4%, P<0.05). On the other hand, at the end of the experimental period, rats that consumed soy protein diets had lower GOT and GPT levels than rats that consumed casein under high-cholesterol diets. Rats that consumed soy protein also had lower total cholesterol (TC) levels in the liver than those that consumed casein under high-cholesterol diets. Rats that consumed the soy protein diet containing both saponin and isoflavone had lower hepatic TC level than those that consumed the soy protein diet without isoflavone alone. The effect of different types of proteins on triglyceride was not significant. Consumption of soy provided benefits to control lipid levels under high-cholesterol dieting conditions in this rat model of hypercholesterolemia. The major component that reduced hepatic TC was not saponin, but possibly isoflavone.

Lipid and glucose utilization in hypercholesterolemic rats fed a diet containing heated chickpea (Cicer aretinum L.): a potential functional food.

This feeding trial evaluated the influence of a diet containing heated chickpea in a dietary induced rat model of hypercholesterolemia in order to assess some possible protective and therapeutic effects on lipid and carbohydrate metabolism disorders as found with other legumes. Rats fed a diet enriched with coconut oil (25%) and cholesterol (1%) for 42 days (HH) showed a situation of type IIa hyperlipoproteinemia. However, these lipid alterations were improved in the hypercholesterolemic rats receiving control (HC) and legume (HL) diets for 16 days. Moreover, results confirm that the chickpea was more effective than the control diet containing casein in the normalization of triglycerides as well as total and LDL-cholesterol levels. On the other hand, the HH group showed a marked reduction in the liver glycogen content and Glucose-6-Phase activity (involved in glyconeogenesis) and an increase in Glucokinase (GK) activity (involved in glucose utilization). In contrast, the rats receiving chickpea re-established the liver glycogen deposition as compared to the HH group. Also, the chickpea intake increased the GK activity as compared to the control diet. The overall results support that chickpea intake may be recommended in humans with altered lipid profile such as type IIa hyperlipoproteinemia. Additionally, data concerning carbohydrate utilization indicated its potential positive effects in diabetes therapy and their role as biological active food supplements.