Rat High Density Lipoprotein Research Articles

Effect of <em>arum manis</em> mango peel extract on cholesterol and triglyceride levels in dyslipidemic Sprague-Dawley rats

BACKGROUND Dyslipidemia is characterized by an increase in low-density lipoprotein (LDL) and triglyceride (TG) levels and a decrease in high-density lipoprotein (HDL). Cholestyramine as an antidyslipidemia has several side effects, so an alternative is needed. Pectin is a natural substance with a mechanism of action similar to that of cholestyramine. Mango peel is one of the sources of pectin, containing 10–15% of this substance. This study aimed to prove the effect of arum manis mango (Mangifera indica L.) peel extract on LDL, HDL, and TG levels in dyslipidemic Sprague-Dawley rats.
 METHODS 25 Sprague-Dawley rats were divided into 5 groups. All groups were given high-fat diet for the first 18 days, followed by standard feed (negative control group), cholestyramine (Sequest®) 80 mg/200 g body weight (standard treatment group), and mango peel extract (M-90 [90 mg/day], M-180 [180 mg/day], and M-360 [360 mg/day] groups) for the next 15 days. LDL and HDL levels were analyzed using the cholesterol oxidase-phenyl aminopyrazolone method and TG level using the glycerol-3-phosphate-oxidase-phenol-aminophenazone method.
 RESULTS The M-360 group reduced the LDL level (p = 0.015), while the standard treatment group increased the HDL level (p = 0.042). Although significant TG level changes were found in the negative control, standard treatment, and M-360 groups (p = 0.042), the mean differences of LDL, HDL, and TG levels between groups were not significantly different (p = 0.245, 0.328, and 0.454, respectively).
 CONCLUSIONS M. indica peel extract reduced LDL and TG levels at 360 mg/day.

Decaffeinated green tea and green coffee extracts as metformin's add-on enhance metabolic syndrome risk factors and improve the cardiac insulin-gene-related pathway

Context: Dysregulation of glucose metabolism in metabolic syndrome (METS) is allegedly due to the disruption of insulin as the main pathway in cellular metabolism. Green tea and green coffee are known to have potential benefit in METS therapy. Aims: To evaluate the effect of therapy using decaffeinated green tea-green coffee extract as metformin's add-on in the risk factors of METS and its effect on the cardiac insulin-gene-related pathway, such as IRS1, PI3Kr1, and GLUT4. Methods: METS model rats were divided into five groups. The rats' level of body weight (BW), fasting blood glucose (FBG), triglycerides (TG), high-density lipoprotein (HDL), insulin (INS), and homeostatic model assessment for insulin resistance (HOMA-IR) were measured periodically. After nine weeks of treatment, the rats were euthanized, and the heart was isolated for measurement of IRS1, PI3Kr1, and GLUT4 gene expression by reverse-transcriptase polymerase chain reaction. Results: This study found that there was a decrease in BW, FBG, TG and an increase in HDL in METS model rats given therapy with metformin and green tea-green coffee extract (COMB) (p<0.0001). There is also improvement in insulin resistance by reducing HOMA-IR in the COMB group (p = 0.0434 for INS and p<0.0001 for HOMA-IR). This study found that IRS1, PI3K, and GLUT4 gene expression increased in the COMB group. The five groups differ significantly, with a p = 0.000. Conclusions: Therapy using a combination of decaffeinated green tea and green coffee extract as an add-on of metformin improved METS risk factor via a significant reduction in BW, FBG, TG, increasing HDL and improving insulin resistance. It also increased the IRS1, PI3Kr1, and GLUT4 gene expression as markers of cardiac insulin-gene-related pathways.

Curcumin Improves Cytokines and HDL in Diabetic Wistar Rats

In type 2 diabetes mellitus, lipid profile is often found in the form of high-density lipoprotein (HDL) decrease. TNFa and IL-6 are proinflammatory cytokines that are elevated in the blood in many patients with diabetes mellitus. Turmeric is one of the natural ingredients that has anti-cholesterol and anti-inflammatory effects through the work of its active substance, curcumin. This study aimed to evaluate the effect of turmeric extract combined with metformin on HDL, TNFa, and IL-6 levels in diabetic rats. Twenty-four Wistar rats were injected intraperitoneally with streptozotocin and niacinamide. The diabetic rats then were divided into four groups; control group, metformin group, turmeric group, and combination group. The dose of metformin and turmeric which were given, respectively, 45mg/KgBW/day and 200 mg/KgBW/day. While the combo group was given half dose of each. Blood serum was taken to examine the HDL, IL-6, and TNFa levels. The levels of HDL, IL-6, TNFa on diabetic rats that received the combination of metformin and turmeric extract (p0.05) were the best among of all the groups. This means that the combination of metformin and turmeric is better in increasing HDL, reducing IL-6, and TNFa levels better than metformin or turmeric extract alone.

Effect of Acupuncture on Simple Obesity and Serum Levels of Prostaglandin E and Leptin in Sprague-Dawley Rats.

Aim The study is aimed at investigating the curative effect of acupuncture on simple obesity and its influence on serum levels of prostaglandin E and leptin in Sprague-Dawley (SD) rats. Methods In the study, there are 50 male SD rats. We took 10 as healthy controls and fed 40 with a diet of high fat for 8 weeks. After the 40 rat model was established successfully, we fed 10 rats in the model group with a normal diet and treated 10 rats in the acupuncture group by acupuncture. During the experiment, the body fat and body length of rats were measured weekly, and Lee's index was calculated. After the treatment, the levels of leptin, prostaglandin E, C-reactive protein (CRP), triacylglycerol (TG), cholesterol (CHO), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were detected, and the liver fat morphology was observed by electron microscope. Results Acupuncture significantly downregulated the serum levels of CRP, TG, CHO, LDL, leptin, and prostaglandin E and upregulated the serum levels of HDL in rats with simple obesity. Conclusion On basis of these results, it was found that acupuncture could boost fat metabolism and weight loss by inhibiting the production of leptin and prostaglandin E.

Myrtenol alleviates oxidative stress and inflammation in diabetic pregnant rats via TLR4/MyD88/NF-κB signaling pathway.

Gestational diabetes mellitus (GDM) is a special kind of diabetes that arises only during pregnancy. A woman with GDM has a higher risk of developing type-2 diabetes and other metabolic diseases. In this exploration, we intended to scrutinize the therapeutic actions of Myrtenol against the streptozotocin (STZ)-provoked GDM in rats. GDM was provoked in the pregnant rats via injecting the 1% of STZ (25 mg/kg) and then treated with the 50 mg/kg of myrtenol. The glucose level and bodyweight of animals were noted. The lipid profile, that is, total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein (HDL) was determined by respective kits. The lipid peroxidation and antioxidants status were examined using assay kits. The status of proinflammatory markers was investigated by assay kits. The messenger RNA (mRNA) expressions of TLR4/MyD88/NF-κB signaling proteins were studied by reverse transcription polymerase chain reaction analysis. The hepatic and pancreatic tissues were examined microscopically. Myrtenol treatment notably decreased the status of blood glucose and lipid profile and improved the HDL in the GDM rats. The status of lipid peroxidation and inflammatory markers were substantially reduced by the myrtenol and it enhanced the antioxidants status of GDM animals. Myrtenol treatment remarkably downregulated the mRNA expressions of TLR4/MyD88/NF-κB signaling proteins. The histological findings also proved the therapeutic actions of myrtenol. Altogether, the findings of this investigation unveiled the therapeutic actions of the myrtenol against the STZ-provoked GDM in rats. Myrtenol could be a promising therapeutic agent to treat GDM in the future.

Study on chemical composition and physical properties of the Hamri (Barbus luteus) and Balaout (Chondrostoma regium) fish meat, oil and impact of its oils on cholesterol, triglyceride, HDL and blood sugar of laboratory rats

The study aimed at investigating the meat chemical composition and physical properties of oil of the Hamri (Barbus luteus) and Balaout (Chondrostoma regium) fish and its oil content or fatty acids, and also to know the impact of its oils on the level of cholesterol, triglyceride, high density lipoprotein (HDL) and blood sugar levels of laboratory rats. The study area extended from the province of Shirqat and Balad district to the province of Salah al-Din. The approximate percentages of meat from Hamri were 72.13, 19.74, 5.07 and 1.60 % for the moisture, protein, fat and ash respectively, and 71.63, 19.98, 4.96 and 2.04% respectively from Balaout. The extract oil from 2 types of fish differed significantly in Iodine value, Peroxide value, and Acid value and in saponification number. The fatty acids profiles results showed that oils from Hamri and Balaout fish meat consisted of 44.31 and 55.76% of Saturated fatty acid, 36.10 and 25.41% of poly unsaturated fatty acid, and 18.17 and 25.41% poly unsaturated fatty acids respectively. The experiment laboratory rats showed decreases in cholesterol, triglyceride and blood sugar level, and increases in high density lipoprotein (HDL). In conclusion, it is recommended that this oil can be used in human diet for health benefits.

Hydrogen influences HDL-associated enzymes and reduces oxidized phospholipids levels in rats fed with a high-fat diet

AimsOxidized phospholipids (OxPLs) are formed as a result of oxidative stress, which potentially mediate multiple pathological effects. We aimed to evaluate the effects of hydrogen (H2) on OxPLs in vivo and the underlying mechanism. Main methodsRats were randomly assigned to three groups: control group fed with a chow diet, model group fed with a high-fat diet, and H2-treated group fed with a high-fat diet and treated by 4% H2 inhalation for ten weeks. OxPLs in liver and plasma were analyzed by liquid chromatography–mass spectrometry. High-density lipoprotein (HDL) was separated by ultracentrifugation. A proteomic analysis was performed to reveal the alternation of HDL protein composition and he antioxidant capacity of HDL was tested by low-density lipoprotein oxidation experiment. Furthermore, the activity or expression of HDL-associated enzymes were evaluated. Key findingsInhalation of 4% H2 decreased the accumulation of OxPLs in rats. In vitro tests revealed that the different concentrations of H2 did not inhibit the formation of OxPLs mediated by non-enzymatic oxidation. H2 inhalation altered the components and enhanced the anti-oxidative capacity of HDL in rats fed with a high-fat diet. Further experiments showed that H2 significantly regulated the activity of lipoprotein-associated phospholipase A2, paraoxonase-1, and the expression of lecithin:cholesterol acyltransferase. SignificanceOur findings revealed that H2 may reduce the OxPLs levels through its influence on HDL-associated enzymes that can act on OxPLs, suggesting that H2 can be used in alleviating diseases related to lipid peroxidation due to oxidative stress.

Evaluation of Sclerorhachis leptoclada hydroalcoholic extract on glucose and cholesterol levels, triglyceride, Serum HDL and LDL in male diabetic rats

Background and Aim: Diabetes is a metabolic disorder in the body. Sclerorhachis leptoclada belongs to the chicory family, is used to treat aids and cancer due to the antioxidant compounds in the root. Therefore, in this study, the effect of hydroalcoholic extract of Sclerorhachis leptoclada on glucose and cholesterol, triglyceride, high density lipoprotein (HDL) and low density lipoprotein (LDL) levels in diabetic rats was investigated. Materials and Methods: In this experimental study, 60 male Wistar rats were randomly divided into 10 groups of 6: Control group, treatment groups 1, 2, and 3 (healthy, treated with 150 mg/kg and 300 and 600 extracts), Diabetic control group, experimental groups 1, 2 and 3 (diabetic, treated with doses of 150 mg/kg and 300 and 600 extracts), Positive control group (diabetic+glibenclamide), The healthy group (healthy+glibenclamide) was divided. After one month of gavage, blood samples were taken from the rats, and glucose, urea, creatinine, and albumin levels were measured. A comparison was made between the effect of hydroalcoholic extract of Sclerorhachis leptoclada and the common drug glibenclamide and the results of the groups were compared by using t-test and ANOVA. Results: The results showed that the administration of hydroalcoholic extract of Sclerorhachis leptoclada can significantly reduce glucose levels in experimental groups (diabetic+extract at doses of 150, 300, 600) compared with the diabetic group (p<0.001) Also, the consumption of hydroalcoholic extract of Sclerorhachis leptoclada in diabetic patients causes a significant reduction in triglyceride, HDL and LDL levels in diabetic rats and has hypoglycemic effects. Conclusion: The results of this study showed that the consumption of hydroalcoholic extract of Sclerorhachis leptoclada in diabetic rats significantly reduces serum levels of glucose, triglyceride and creatinine in diabetic rats and has hypoglycemic effects

Comparative Study of the Effects of Annona muricata and Tapinanthus globiferus Extracts on Biochemical Indices of Diabetic Rats

Introduction: Annona muricata and Tapinanthus globiferus (mistletoe) are medicinal plants used in traditional medicine to combat an array of human diseases. However, there is dearth of scientific prove for the activity of these plants in the management of non-infectious human diseases such as cancer, insomnia, hypertension, ulcers and diabetes. Method: The present study was designed to assess comparatively the effects of methanol extracts of Annona muricata (AME) and Tapinanthus globiferus (TGE) on biochemical indices of alloxan induced diabetic rats. The animals were allocated to eight (8) groups, group I were normal non-diabetic rats, group II (diabetic untreated group), group III treated with metformin alone, groups IV & V were diabetic rats treated with AME at dose of concentration 200 mg/kg BW & 400 mg/kg BW respectively, groups VI & VII were diabetic rats treated with 200 mg/kg BW & 400 mg/kg BW of TGE respectively. Group VIII were diabetic rats treated with AME + TGE at concentration of 200 mg/kg BW each. Concentrations of serum total cholesterol (TC), high density lipoprotein (HDL), triglyceride (TG) of alloxan diabetic rats, creatinine and urea were assayed after 21 days of the respective treatments. Results: Diabetic untreated rats had significant increase p<0.05 in TC, TG, urea and creatinine compared to normal control group as opposed to the significant decrease observed for HDL in diabetic rats. However, treatment of diabetic rats with AME and TGE significantly suppressed (p<0.05) the concentrations of TC, TG and creatinine when compared with the diabetic untreated rats. A similar trend was observed for the calculated atherogenic index of treated rats when compared with diabetic untreated rats. Interestingly, co-administration of AME + TGE improved the biochemical indices of diabetic rats better than using each plant separately. Conclusion: The results of this study suggest that AME and TGE could offer some benefits in the management of diabetic complications especially with regard to cardiac and renal health.

Toxicological Profile of Carbamazepine and Levetiracetam on Some Biochemical and Haematological Parameters in Rats

The prolonged usage of antiepileptic drugs has necessitated the need to study their toxicological profiles using in experimental animals. The toxicological effects of carbamazepine (CBZ) and levetiracetam (LEV) on some biochemical and haematological parameters were evaluated in rats. Haematological parameters evaluated include packed cell volume (PCV), Haemoglobin (Hb) and white blood cell (WBC), while some biochemical parameters studied were liver enzyme tests such as alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipid profiles tests such as total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL). In addition, the body weight and morphological assessment of the vital body organs were determined. Results showed that CBZ and LEV did not significantly affect the haematological parameters. Animals treated with CBZ showed a significant increase in TC and HDL levels at 400 and 1000 mg/kg doses. There was no significant increase in the TC, HDL, LDL and TG in rats treated with LEV. CBZ and LEV treated animals at the doses of 400 and 1000 mg/kg showed a significant increase in body weights from the 6th day after commencement of treatment. There was also a significant increase in the weights of the liver, kidney and heart of the animals treated with CBZ and LEV. The colour and texture of the organs did not change. However, no appreciable weight increase was observed with the lung.

Combined Effects of Curcumin and Lycopene or Bixin in Yoghurt on Inhibition of LDL Oxidation and Increases in HDL and Paraoxonase Levels in Streptozotocin-Diabetic Rats.

Combination therapy using natural antioxidants to manage diabetes mellitus and its complications is an emerging trend. The aim of this study was to investigate the changes promoted by treatment of streptozotocin (STZ)-diabetic rats with yoghurt enriched with the bioactives curcumin, lycopene, or bixin (the latter two being carotenoids). Antioxidants were administered individually, or as mixtures, and biomarkers of metabolic and oxidative disturbances, particularly those associated with cardiovascular risk, were assessed. Treatment of STZ-diabetic rats with natural products individually decreased glycemia, triacylglycerol, total-cholesterol, oxidative stress biomarkers, including oxidized low-density lipoprotein (ox-LDL), and increased the activities of antioxidant enzymes. Individual carotenoids increased both high-density lipoprotein (HDL) and paraoxonase levels, whereas curcumin increased only paraoxonase. Treatments with mixtures of curcumin and lycopene or bixin had combined effects, decreasing biomarkers of carbohydrate and lipid disturbances (curcumin effect), increasing the HDL levels (carotenoids effects) and mitigating oxidative stress (curcumin and carotenoids effects). The combined effects also led to prevention of the LDL oxidation, thereby mitigating the cardiovascular risk in diabetes. These findings provide evidence for the beneficial effect of curcumin and carotenoid mixtures as a supplementation having antioxidant and antiatherogenic potentials, thus appearing as an interesting strategy to be studied as a complementary therapy for diabetic complications.

Efficacy of fenofibrate for hepatic steatosis in rats after severe burn

Efficacy of fenofibrate for hepatic steatosis in rats after severe burn

Effects and relationship of intermittent hypoxia on serum lipid levels, hepatic low-density lipoprotein receptor-related protein 1, and hypoxia-inducible factor 1α.

This study investigated the influence of intermittent hypoxia on serum lipid level, hepatic low-density lipoprotein receptor-related protein (LRP)1, and hepatic hypoxia-inducible factor (HIF)-1α and the underlying mechanisms of action. Male Sprague Dawley rats were subjected to different levels of hypoxia. After 1-4 weeks hypoxemia, routine blood tests were performed and the levels of LRP1 and HIF-1α in liver were examined. Intermittent hypoxia (IH) was induced in HepG2 cells with or without HIF-1α inhibitor YC-1 pretreatment, and the levels of LRP1 and HIF-1α in cells were examined. IH caused elevated serum triglyceride, cholesterol, low-density lipoprotein, and high-density lipoprotein in rats. IH caused elevated hepatic levels of LRP1 and HIF-1α. After pretreatment with YC-1, HIF-1α protein expression decreased but mRNA expression did not change in HepG2 cells. IH caused dyslipidemia and elevated LRP1 and HIF-1α. Elevated LRP1 expression was caused by HIF-1α.

Houttuynia cordata alleviates high-fat diet-induced non-alcoholic fatty liver in experimental rats

Context: Houttuynia cordata Thunb. (Saururaceae) is used traditionally in Asian countries to treat various disease symptoms.Objective: To study the effect of H. cordata ethyl acetate (HC-EA) extract on high-fat diet (HFD)-induced hepatic steatosis.Materials and methods: HFD fed rats were orally dosed with HC-EA (100, 200, or 300 mg/kg) once daily for 8 weeks and the lipid profiles and protein expressions in hepatocytes were evaluated.Results: HFD rats showed an increase (p < 0.05) in the plasma lipid levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), free fatty acids (FFAs), and reduced the high-density lipoprotein (HDL) levels. Treatment with HC-EA extract (300 mg/kg) restored the changes in plasma lipid levels of TC, TG, LDL, FFA, and HDL in HFD-fed rats by 34.8, 31.1, 51.4, 32.4, and 56.3%, respectively, compared with control rats (p < 0.01). HC-EA treatment also decreased the hepatic lipid accumulation (p < 0.001 at 300 mg/kg) and improved hepatic histological lesions. HC-EA extract enhanced AMPK phosphorylation and its primary downstream targeting enzyme, acetyl-CoA carboxylase (ACC), up-regulated the gene expression of carnitine palmitoyl transferase-1 (CPT-1), and down-regulated sterol regulatory element binding protein 1, fatty acid synthase, and glutamate pyruvate transaminase protein levels in the livers of HFD-fed rats. Further, the increased expression of hepatic cytochrome P450 (CYP) composition such as CYP2E1 and CYP4A was also suppressed.Discussion and conclusion: Data suggest that HC-EA extract might act by regulating the AMPK-dependent pathway and related mediators and might be used in treating obesity-related liver diseases.

Combination of Capsaicin and Vitamin E Increase HDL and Decrease LDL Levels in Hypercholesterolemic Rats

Cardiovascular disease was the most lethal disease in the world. Atherosclerosis was one of the factor that can lead to the development of cardiovascular disease. Low density lipoprotein (LDL) and high density lipoprotein (HDL) were often associated with atherosclerosis. LDL and HDL concentration can be modified by diet, such as capsaicin and vitamin E. In this study, 25 male Sprague Dawley rats were divided into 5 group, A, B, C, D and E. Each group had 5 rats. Group B, C, D, and E were rendered high fat diet (A.D. II standard diet, 10% lard, olive oil and yolk) for 14 days while group A was given standard diet. Group B was positive control and get no treatment, group C was given 1 mg/kg capsaicin for 14 days, group D was given 22 IU vitamin E. LDL and HDL concentration were measured before and after the treatment. LDL concentration decreased significantly and HDL concentration increased insignificantly after capsaicin treatment. LDL and HDL concentration were significantly increase after given 22 IU vitamin E. Combination of 1 mg/ kg capsaicin and 22 IU vitamin E could also improve HDL concentration and reduce LDL concentration. Vitamin E gave the best effect when compare with capsaicin alone and the combination of capsaicin and vitamin E in increasing HDL concentration and reducing LDL concentration.

Scientific Validation of Antidiabetic Activity of Ethanol Extract of Ficus glomerata Barks and Roots in Streptozotocin-Induced Diabetic Rats

The tribal people of Chhattisgarh state of India use Ficus glomerata for the treatment of diabetes therefore we planned to investigate antidiabetic effect of bark and root extract of bark and root in Streptozotocin (STZ)-induced diabetic rats. Oral administration of ethanol extract of bark and root of Ficus glomerata at the doses of 200 and 400 mg/kg body weight was studied in STZ-induced diabetic rats. After administration of extract the fasting blood glucose levels were significantly decreased. The oral glucose tolerance was also improved. The effect of extracts on serum lipid profile like total cholesterol, triglycerides, low density lipoprotein (LDL) and high density lipoprotein (HDL) were also measured in the diabetic and non diabetic rats. There was significant reduction in total cholesterol, LDL and improvement in HDL in diabetic rats were observed. The activity of the plant extracts was comparable with glibenclamide, a well-known antidiabetic drug. These results indicated that Ficus glomerata possesses significant antidiabetic and antihyperlipidemic effect.

Effect of Cholesterol Enriched or Fatty-Acid Diets on Cholesterol and Lipid Levels in Young Wistar Rats

Nutritional intake is a fundamental determinant of health. It is well known that cholesterol rich diets can induce several pathological conditions but detailed mechanism underlying these remains unknown. Wistar rats, an animal strain widely used in the research have been employed to study the effects of dietary interventions due to their metabolic characteristics, which are closer to the human compared to mice. The effect of some components of the western diet, combined with cholesterol in the lipid profile have been studied, but the impact of only cholesterol or fatty-acid diets in such a profile has not been yet characterized. Here we measured the effect of 6 or 16 weeks of dietary intervention with cholesterol enriched diet (CED) or fatty-acid diet (FAD) on cholesterol, triglyceride levels, high density lipoproteins (HDL) and low density lipoproteins (LDL). We observed significant differences in body weight only in animals treated with CED or FAD from Week 9 onwards as compared to animals fed the control diet. There were no differences between animals fed with CED or FAD in cholesterol levels at any time point nevertheless, triglyceride levels were significantly increased as compared to control diet in animals under both diets at early time points. Finally, both CED and FAD induced a decrease in HDL as compared to control levels in treatments of more than 6 weeks, whereas LDL transiently increased in animals treated with FAD from 10 to 12 weeks, but after this period LDL levels returned to baseline, suggesting that young rats have a compensatory effect at least for the period of time analyzed here. Here we provide a temporal course on lipid profile of cholesterol, triglycerides, HDL and LDH in Wistar rats treated with CED and FAD diet that can be useful as reference for future studies.

Anti–trypanosomal effect of Peristrophe bicalyculata extract on Trypanosoma brucei brucei–infected rats

ObjectiveTo investigate the in vitro and in vivo effect of whole plant extracts of Peristrophe bicalyculata on Trypanosoma brucei brucei-infected rats. MethodsThe experiment was divided into two phases: In the first phase, the anti-trypanosomal activity of the hot water, cold water, methanol and butanol extracts of the whole plant were determined by incubating with Trypanosoma brucei brucei. The cold water extract was partially-purified and the anti-trypanosomal activity of the fractions determined. In the second phase, Trypanosoma brucei brucei-infected rats were treated with fraction 2c for nine days. Packed cell volume (PCV), high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol (TC), triacylglycerol (TAG), aspartate aminotransferase, alanine aminotransferases (ALT), alkaline phosphatase (ALP), total and direct bilirubin levels were determined at the end of the experiment. ResultsCold water extract immobilized 90% of the parasites after 60 min of incubation, and fraction 2c completely immobilized the parasites after 35 min. It significantly increased PCV in Trypanosoma brucei brucei-infected rats. Decreased TC, TAG, HDL and LDL levels of infected rats increased significantly when rats were treated with the fraction, while elevated levels of total bilirubin and ALT also decreased. The difference in urea, direct bilirubin and ALP was not significant when infected rats were compared to rats in other groups. ConclusionsThe ability of the plant to ameliorate the infection-induced biochemical changes calls for detailed investigation of the potentials of the plant for antitrypanosomiasis drug delivery.

Postprandial Changes in High Density Lipoproteins in Rats Subjected to Gavage Administration of Virgin Olive Oil

Background and AimsThe present study was designed to verify the influence of acute fat loading on high density lipoprotein (HDL) composition, and the involvement of liver and different segments of small intestine in the changes observed.Methods and ResultsTo address these issues, rats were administered a bolus of 5-ml of extra-virgin olive oil and sacrificed 4 and 8 hours after feeding. In these animals, lipoproteins were analyzed and gene expressions of apolipoprotein and HDL enzymes were assessed in duodenum, jejunum, ileum and liver. Using this experimental design, total plasma and HDL phospholipids increased at the 8-hour-time-point due to increased sphingomyelin content. An increase in apolipoprotein A4 was also observed mainly in lipid-poor HDL. Increased expression of intestinal Apoa1, Apoa4 and Sgms1 mRNA was accompanied by hepatic decreases in the first two genes in liver. Hepatic expression of Abcg1, Apoa1bp, Apoa2, Apoe, Ptlp, Pon1 and Scarb1 decreased significantly following fat gavage, while no changes were observed for Abca1, Lcat or Pla2g7. Significant associations were also noted for hepatic expression of apolipoproteins and Pon1. Manipulation of postprandial triglycerides using an inhibitor of microsomal transfer protein -CP-346086- or of lipoprotein lipase –tyloxapol- did not influence hepatic expression of Apoa1 or Apoa4 mRNA.ConclusionAll these data indicate that dietary fat modifies the phospholipid composition of rat HDL, suggesting a mechanism of down-regulation of hepatic HDL when intestine is the main source of those particles and a coordinated regulation of hepatic components of these lipoproteins at the mRNA level, independently of plasma postprandial triglycerides.

Harnessing a Physiologic Mechanism for siRNA Delivery With Mimetic Lipoprotein Particles

Therapeutics based on RNA interference (RNAi) have emerged as a potential new class of drugs for treating human disease by silencing the target messenger RNA (mRNA), thereby reducing levels of the corresponding pathogenic protein. The major challenge for RNAi therapeutics is the development of safe delivery vehicles for small interfering RNAs (siRNAs). We previously showed that cholesterol-conjugated siRNAs (chol-siRNA) associate with plasma lipoprotein particles and distribute primarily to the liver after systemic administration to mice. We further demonstrated enhancement of silencing by administration of chol-siRNA pre-associated with isolated high-density lipoprotein (HDL) or low-density lipoprotein (LDL). In this study, we investigated mimetic lipoprotein particle prepared from recombinant apolipoprotein A1 (apoA) and apolipoprotein E3 (apoE) as a delivery vehicle for chol-siRNAs. We show that apoE-containing particle (E-lip) is highly effective in functional delivery of chol-siRNA to mouse liver. E-lip delivery was found to be considerably more potent than apoA-containing particle (A-lip). Furthermore, E-lip–mediated delivery was not significantly affected by high endogenous levels of plasma LDL. These results demonstrate that E-lip has substantial potential as delivery vehicles for lipophilic conjugates of siRNAs.