Methods: Inbred mice received saline, DMSO and amygdalin, as control groups. ER stress was induced by tunicamycin (TM) injection. Amygdalin was administered 1 h before the TM challenge (Amy + TM group). Mice body and liver weights were measured. Hematoxylin and eosin (H&E) and oil red O staining from liver tissue, were performed. Alanin aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride and cholesterol levels were measured.
Results: Histological evaluation revealed that amygdalin was unable to decrease the TM induced liver steatosis; however, ALT and AST levels decreased [ALT: 35.33(2.15) U/L versus 92.33(6.66) U/L; (57.000, (50.63, 63.36),P< 0.001) and AST: 93(5.09) U/L versus 345(97.3) U/L, (252, (163.37, 340.62),P< 0.001)]. Amygdalin also decreased triglyceride and cholesterol plasma levels in the Amy + TM group [TG: 42.66(2.15) versus 53.33(7.24) mg/dL; (10.67, (3.80, 17.54),P= 0.006) and TC: 9.33(3.55) versus 112.66(4.31) mg/dL, (103.33, (98.25, 108.40)P< 0.001)].
Conclusion: Amygdalin improved the ALT, AST, and lipid serum levels after the TM challenge; however, it could not attenuate hepatic steatosis.
HYPOTHESIS/PURPOSE: We hypothesized that LPva extracts can modulate the lipid profiles and serum antioxidant status of hypercholesterolemic rats. In the present study, we investigated the effects of aqueous and 80% ethanol extracts of LPva on atherogenic and serum antioxidant parameters as well as changes in abdominal aorta of high-cholesterol diet rats.
METHODS: The major components of the extracts, gallic acid, flavonoids and alkyl resorcinols were analyzed by using a validated reversed phase HPLC method. The rats were induced to hypercholesterolemic status with daily intake of 2% cholesterol for a duration of 8 weeks. Three different doses (100, 200 and 400mg/kg) of the extracts were administered daily on the 4th week onwards. The rats were then sacrificed and the blood was collected via abdominal aorta and serum was separated by centrifugation for biochemical analysis. Part of the aorta tissues were excised immediately for histopathological examination.
RESULTS: The serum of LPva treated rats showed significant reduction in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels and the abdominal aorta showed a significant decrease of atheroma lesions in treated rats. Serum lipid profiles of treated rats showed a decrease in total cholesterol, total triglycerides and low-density lipoprotein (LDL) levels as compared to control group. The atherogenic indices in treated rats were significantly improved along with an increasing level of serum high-density lipoprotein (HDL). The extracts also exhibited significant increase of antioxidant enzymes and decrease of MDA as a product of lipid peroxidation.
CONCLUSION: LPva extracts can reduce the risk of dyslipidemia by improving the serum lipid profiles and modulating serum antioxidants.
PURPOSE: In this study, we aimed to discover the role of oil palm phenolics (OPP) in influencing the gene expression changes caused by an atherogenic diet in mice.
METHODS: We fed mice with either a low-fat normal diet (14.6 % kcal/kcal fat) with distilled water, or a high-fat atherogenic diet (40.5 % kcal/kcal fat) containing cholesterol. The latter group was given either distilled water or OPP. We harvested major organs such as livers, spleens and hearts for microarray gene expression profiling analysis. We determined how OPP changed the gene expression profiles caused by the atherogenic diet. In addition to gene expression studies, we carried out physiological observations, blood hematology as well as clinical biochemistry, cytokine profiling and antioxidant assays on their blood sera.
RESULTS: Using Illumina microarrays, we found that the atherogenic diet caused oxidative stress, inflammation and increased turnover of metabolites and cells in the liver, spleen and heart. In contrast, OPP showed signs of attenuating these effects. The extract increased unfolded protein response in the liver, attenuated antigen presentation and processing in the spleen and up-regulated antioxidant genes in the heart. Real-time quantitative reverse transcription-polymerase chain reaction validated the microarray gene expression fold changes observed. Serum cytokine profiling showed that OPP attenuated inflammation by modulating the Th1/Th2 axis toward the latter. OPP also increased serum antioxidant activity to normal levels.
CONCLUSION: This study suggests that OPP may possibly attenuate atherosclerosis and other forms of cardiovascular disease.
MATERIALS AND METHODS: This was a cross-sectional, single center study. A total of 110 subjects between 18 to 65 years of age and diagnosed with OSA following sleep study examinations were recruited. Exclusion criteria included seropositive Hepatitis B or Hepatitis C, and significant alcohol intake.
RESULT: The prevalence of NAFLD was 81.8%. The mean CIMT (0.08±0.03 vs 0.06±0.01 cm, p = 0.001), ICAM-1 (334.53±72.86 vs 265.46±102.92 ng/mL, p = 0.001) and Lp(a) (85.41±52.56 vs 23.55±23.66 nmol/L, p<0.001) were significantly higher in the NAFLD group compared to the non-NAFLD group. Comparisons between the different groups showed significantly increasing levels of CIMT, ICAM-1 and Lp(a), lowest within the non-NAFLD, followed by the NAFLD 1 and NAFLD 2+3 groups. There was a significant positive correlation between degree of steatosis and the severity of OSA (r = 0.453, p<0.001). Logistic regression analysis revealed that patients with apnea/hypopnea index (AHI) of >30 were 52.77 (CI 6.34, 439.14) times more likely to have NAFLD compared to those with mild AHI (p<0.001).
CONCLUSION: The prevalence of NAFLD is alarmingly high in this group of OSA patients. The degree of steatosis in patients with NAFLD was significantly correlated with severity of OSA, CIMT measurements, ICAM-1 and Lp(a). Our findings underscore screening for NAFLD in patients with OSA to ensure prompt risk stratification and management.
AIM OF THE STUDY: The present study was performed to determine underlying mechanism of G. procumbens ethanol extract and its fractions such as aqueous, chloroform, ethyl acetate and hexane affect macrophage derived foam cell formation.
MATERIALS AND METHODS: Lipid droplets accumulation in treated macrophages were visualized by Oil Red O staining while the total cholesterol present in the treated macrophages were measured using Cholestryl Ester quantification assay kit. Enzyme-Linked Immunosorbent Assay (ELISA) were used to detect TNF-α and IL-1β secretion in the supernatant of treated macrophages. Gene expression of Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and ATP-binding cassette transporter A-1 (ABCA-1) in treated macrophages were analyzed using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR).
RESULTS: G. procumbens ethanol extract and its fractions reduced lipid droplet accumulation and total cholesterol in oxLDL-treated macrophages together with significantly reduction of TNF-α and IL-1β secretions in supernatant oxLDL-treated macrophages. LOX-1 gene expression was significantly reduced when G. procumbens ethanol extract and its fractions were added in oxDL-treated macrophages. In contrast, G. procumbens ethanol extract and its fractions significantly increased the expression of ABCA-1 gene in oxLDL-treated macrophages.
CONCLUSION: In conclusion, G. procumbens ethanol extract and its fractions inhibit the formation of macrophage derived foam cell by reducing TNF-α and IL-1β expression, which usually highly expressed in atherosclerotic plaques, suppressing scavenger receptor LOX-1 gene that binds oxLDL but induced ABCA-1 gene that mediate lipid efflux from macrophages.
METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months.
RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group.
CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).
AIM: The study aimed to investigate the effect of P.s on atherosclerotic changes in hypercholesterolemic rabbits.
METHODS: Forty two male New Zealand white rabbits were divided into seven groups. C - control group fed normal rabbit chow, CH - cholesterol diet (1% cholesterol), W1 - 1% cholesterol with water extract of P.s (62.5 mg/kg), W2 - 1% cholesterol with water extract of P.s (125 mg/kg), W3 - 1% cholesterol with water extract of P.s (250 mg/kg), W4 - 1% cholesterol with water extract of P.s (500 mg/kg) and Smv - 1% cholesterol supplemented with simvistatin drug (1.2 mg/kg). All rabbits were treated for 10 weeks. Following 10 weeks of supplementation, the animals were sacrificed and the aortic tissue was taken for histological study.
RESULTS: Rabbits fed only with high cholesterol diet 1% cholesterol (CH) showed focal fatty streak lesions compared to the C group and 1% cholesterol supplemented with simvistatin drug (Smv) group. Atherosclerotic lesions in the 1% cholesterol group supplemented with P.s (500 mg/kg) i.e. W4 group showed significant reduction (30 + or - 6.0%, p < 0.05) in fatty streak compared to the high cholesterol group (85.6 + or - 4.1%) under Sudan IV stain. The atherosclerotic lesions under transmission electron microscope showed reduction in foam cells in the treatment groups compared to the CH groups.
CONCLUSION: Administration of P.s extract has protective effect against atheroscleros.