Biomedical subjects

Kailash Prasad

Publications and source records attributed to Kailash Prasad.

13 recordsLinked to original sources

PubMed2006

Secoisolariciresinol diglucoside: relevance to angiogenesis and cardioprotection against ischemia-reperfusion injury.

Therapeutic angiogenesis represents a novel approach for the prevention and treatment of ischemic heart disease. This study examined a novel method of stimulating myocardial angiogenesis using secoisolariciresinol diglucoside (SDG), a plant lignan isolated from flaxseed. SDG has been shown to decrease serum cholesterol and reduce the extent of atherosclerosis. In the present study, the angiogenic properties of SDG were investigated in three different models. First, in the in vitro model, human coronary arteriolar endothelial cells (HCAEC) treated with SDG (50 and 100 microM) showed a significant increase in tubular morphogenesis compared with control. Western blot analysis indicated an increased expression of vascular endothelial growth factor (VEGF), kinase insert domain-containing receptor (KDR), Flt-1, angiopoietin-1 (Ang-1), Tie-1, and phosphorylated endothelial nitric oxide synthase (p-eNOS) in the SDG-treated cells. Second, in the ex vivo ischemia/reperfusion model, SDG-treated rats (20 mg/kg b.wt./day for 2 weeks orally) showed an increased level of aortic flow and functional recovery after 2 h of reperfusion following 30 min of ischemia compared with the control group [dP/dt (mm Hg/s) of 2110 +/- 35 versus 1752 +/- 62]. SDG reduced infarct size compared with the control group by 32% (38 versus 26%) and also decreased cardiomyocyte apoptosis. Increased protein expression of VEGF, Ang-1, and p-eNOS was also observed in the SDG-treated group. Third, in the in vivo myocardial infarction model, SDG increased capillary density and myocardial function as evidenced by increased fractional shortening and ejection fraction. In conclusion, these results suggest that SDG has potent angiogenic and antiapoptotic properties that may contribute to its cardioprotective effect in ischemic models.

Animals↗

PubMed2006

Suppression of hypercholesterolemic atherosclerosis by pentoxifylline and its mechanism.

Reactive oxygen species (ROS) have been implicated in the development of hypercholesterolemic atherosclerosis. Hypercholesterolemia increases the levels of platelet activating factor (PAF) and cytokines which are known to stimulate granulocytes and endothelial cells to produce ROS. Pentoxifylline (PTX) is an inhibitor of cytokines and PAF and would reduce the generation of ROS by granulocytes and endothelial cells. PTX therefore would be expected to reduce the development of hypercholesterolemic atherosclerosis. New Zealand white female rabbits were assigned to four groups: Group I (n=12), control; Group II (n=5), PTX control (40 mg/kg body weight daily orally); Group III (n=13), 0.5% cholesterol; Group IV (n=9), 0.5% cholesterol+PTX (40 mg/kg body weight daily orally). Blood samples were collected before (0 time) and after 1 and 2 months on experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), LDL-C, HDL-C and serum malondialdehyde (MDA), a lipid peroxidation product. At the end of 2 months the aorta was removed for measurement of atherosclerotic plaques, MDA, and aortic tissue chemiluminescence (Ao-CL), a marker for antioxidant reserve. Rabbits in Group III developed atherosclerosis (56.61+/-6.90% of the intimal surface of aorta was covered with atherosclerotic plaques) which was associated with an increase in the serum TG, TC, LDL-C, HDL-C, TC/HDL-C, MDA and aortic MDA and antioxidant reserve. PTX reduced the development of atherosclerosis by 38.1% and this was associated with decreases in serum MDA by 32%, aortic MDA by 37%, and antioxidant reserve by 17.3% without changes in the serum lipids. These results suggest that ROS generated during hypercholesterolemia via cytokines and PAF may in part contribute to the development of hypercholesterolemic atherosclerosis and that suppression of production and activity of cytokines and PAF may reduce the development of hypercholesterolemic atherosclerosis.

Animals↗

PubMed2006

C-reactive protein (CRP)-lowering agents.

C-reactive protein (CRP) plays a role in the pathogenesis of cardiovascular disease. It is a marker and predictor of cardiovascular disease. CRP possesses numerous cardiovascular effects (clotting, generation of oxygen radicals, increase in the expression of adhesion molecules and plasminogen activator inhibitor-1, plaque destabilization) that could result in cardiovascular disease. This review describes the effects of various cardiovascular drugs on the levels of CRP in health and disease. Cyclooxygenase inhibitors (aspirin, rofecoxib, celecoxib), platelet aggregation inhibitors (clopidogrel, abciximab), lipid lowering agents (statins, ezetimibe, fenofibrate, niacin, diets), beta-adrenoreceptor antagonists and antioxidants (vitamin E), as well as angiotensin converting enzyme (ACE) inhibitors (ramipril, captopril, fosinopril), reduce serum levels of CRP; while enalapril and trandolapril have not been shown to have the same effect. Angiotensin receptor blockers (ARBs) (valsartan, irbesartan, olmesartan, telmisartan) markedly reduce serum levels of CRP. The findings with other ARBs (losartan and candesartan) were inconsistent. Antidiabetic agents (rosiglitazone and pioglitazone) reduce CRP levels, while insulin is ineffective. Calcium channel antagonists have variable effects on CRP levels. Hydrochlorothiazide and oral estrogen do not affect CRP. The CRP-lowering effect of statins is more pronounced than their lipid lowering effect and is not dependent on their hypolipemic activity. The effect of atorvastatin on CRP seems to be dose-dependent. CRP-lowering effect of statins is likely to contribute to the favorable outcome of statin therapy. The data suggest that lipid lowering agents, ACE inhibitors, ARBs, antidiabetic agents, antiinflammatory and antiplatelet agents, vitamin E, and beta-adrenoreceptor antagonists lower serum or plasma levels of CRP, while vitamin C, oral estrogen and hydrochlorothiazide do not affect CRP levels.

Adrenergic beta-Antagonists↗

PubMed2006

Oxidative stress in renal transplant patients who develop cardiovascular disease.

Cardiovascular disease limits life expectancy of successful renal transplant patients. Reactive oxygen species have been implicated in the development of atherosclerosis, and high levels could be due to increased production or a decrease in antioxidant reserve. Cardiovascular disease in renal transplant recipients could be due to elevated levels of malondialdehyde (an index of levels of reactive oxygen species) and homocysteine and reduced levels of glutathione. Renal transplant recipients with and without cardiovascular disease were studied along with healthy controls. Serum malondialdehyde, plasma homocysteine, and red blood cell glutathione were measured. The results suggest that levels of serum malondialdehyde and plasma homocysteine were higher in patients with or without cardiovascular disease compared with controls; however, the values were similar in both groups of transplant patients. Glutathione levels in red blood cells were similar in all 3 groups. Renal transplant recipients without cardiovascular disease have high levels of oxidative stress and may develop cardiovascular disease with time.

Adult↗

PubMed2005

Hypocholesterolemic and antiatherosclerotic effect of flax lignan complex isolated from flaxseed.

Hypercholesterolemia, low HDL-C and oxygen radicals have been implicated in the development of atherosclerosis. Lignan complex isolated from flaxseed contains secoisolariciresinol diglucoside (SDG), 3-hydroxy-3methylglutaric acid (HMGA) and cinnamic acids. SDG and cinnamic acids are antioxidants, and HMGA is a hypocholesterolemic agent. Antioxidants are known to reduce hypercholesterolemic atherosclerosis. The objectives of this study were to determine if lignan complex reduces (i) serum cholesterol, (ii) oxidative stress, and (iii) atherosclerosis in hypercholesterolemic rabbits. Rabbits were assigned to four groups: Group I, control; Group II, lignan complex control (lignan complex, 40 mg/kg body weight daily orally); Group III, 0.5% cholesterol; Group IV, 0.5% cholesterol diet+lignan complex, (40 mg/kg body weight daily orally). Blood samples were collected before (time 0) and after 1 and 2 months of experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), LDL-C, HDL-C and serum malondialdehyde (MDA), a lipid peroxidation product. At the end of the protocol, the aorta was removed for measurement of atherosclerotic plaques, MDA and aortic tissue chemiluminescence (Aortic CL), a marker of antioxidant reserve. Rabbits in Group III developed atherosclerosis (50.84+/-6.23% of the intimal surface of the aorta was covered with atherosclerotic changes) which was associated with an increase in the serum TG, TC, LDL-C, HDL-C, MDA and aortic MDA and antioxidant reserve. Lignan complex reduced the development of atherosclerosis by 34.37% and this was associated with a decrease in serum TC by 20%, LDL-C by 14%, TC/HDL-C by 34%, serum MDA by 35% and aortic MDA by 58%. Serum HDL-C was elevated by 30% in hypercholesterolemic rabbits and by 25% in normocholesterolemic rabbits with lignan complex. Lignan complex did not affect the TC and LDL-C and serum MDA in the normocholesterolemic rabbits. However, it increased the aortic MDA in the normocholesterolemic rabbits. These results suggest that lignan complex isolated from flaxseed reduced the extent of hypercholesterolemic atherosclerosis and this effect was associated with marked decreases in oxidative stress, serum total cholesterol, LDL-C and risk ratio, and elevation of serum HDL-C. Lignan complex may, therefore, be beneficial in preventing atherosclerosis, and reducing risk factors for coronary artery disease and stroke.

Animals↗

PubMed2005

Effect of chronic administration of lignan complex isolated from flaxseed on the hemopoietic system.

Lignan complex has been isolated from flaxseed. It has been shown to reduce serum lipids and the extent of hypercholesterolemic atherosclerosis. However, it is not known whether the chronic use of lignan complex has any adverse effects on the hemopoietic system. The effects of lignan complex (40 mg/kg body wt orally daily for 2 months) on the red blood cells (RBC) count, mean corpuscular volume (MCV), red cell distribution width (RDW), hematocrit (Hct), hemoglobin (Hb), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and counts of white blood cell (WBC), granulocytes, lymphocytes, monocytes and platelet, and platelet volume were investigated in normo- and hypercholesterolemic rabbits. The results show that lignan complex had no adverse effects of counts of RBC, WBC, granulocytes, lymphocytes, monocytes and platelet in both the normo- and hyper-cholesterolemic rabbits. The values for MCV, RDW, Hct, Hb, MCH, MCHC, and platelet volume were similar in lignan complex-treated or untreated normo- and hypercholesterolemic rabbits. It is concluded that chronic use of lignan complex had no adverse effects on the hemopoietic system.

Analysis of Variance↗

PubMed2005

Effect of flaxseed consumption on blood pressure, serum lipids, hemopoietic system and liver and kidney enzymes in healthy humans.

BACKGROUND: Effects of flaxseed on serum lipids have been studied in humans, but the results are variable. Flaxseed is ineffective in lowering blood pressure in rats. Its effect on blood pressure in humans is not known. It is also not known if long-term use of flaxseed in humans has deleterious effects on the hemopoietic system, serum glucose, and renal and kidney function. We investigated the effect of short-term use of flaxseed in humans on arterial pressure and serum lipids (triglycerides, total cholesterol; high-, low-, and very-low-density-lipoprotein cholesterol [HDL-C, LDL-C, VLDL-C], hemopoietic system (red blood cells, neutrophils, hemoglobin) and the various biochemical parameters, such as serum protein, albumin, total bilirubin, aspartate aminotransferase, alkaline phosphatase, creatinine, urea, related to hepatic and renal function, and serum glucose. METHODS: Fifteen healthy men, aged 22 to 47 years, consumed three muffins daily containing 32.7 g of total flaxseed for 4 weeks, in addition to their normal daily diet. Blood pressure and blood samples for various biochemical measurements were collected before and after 4 weeks of flaxseed diet. RESULTS: Blood pressures, heart rate, hemoglobin, and counts of red blood cells, white blood cells, and neutrophils remained unaltered after flaxseed diet. Serum total cholesterol, HDL-C, LDL-C, and VLDL-C remained unchanged, but serum triglycerides levels were elevated. Serum total bilirubin, aspartate aminotransferase, alkaline phosphatase, protein, albumin, glucose, and urea remained unaltered, but serum levels of creatinine decreased. CONCLUSION: These results suggest that 4 weeks use of flaxseed does not have deleterious effects on the hemopoietic system or renal and hepatic function and does not lower blood pressure and serum lipids. However, the level of serum triglyceride level was elevated.

Adult↗

PubMed2004

C-reactive protein increases oxygen radical generation by neutrophils.

C-reactive protein (CRP) has been suggested to play a role in the pathogenesis of atherosclerosis. Neutrophil respiratory burst and levels of CRP are increased during infection. The increase in the neutrophil respiratory burst may be due to factors that are elevated in infection, such as cytokines, tumor necrosis factor, platelet-activating factor, and CRP. The direct effect of CRP on the release of oxygen radicals by neutrophils is not known. This investigation was made to determine if CRP affects the generation of oxygen radicals by neutrophils and if this effect is blocked by antioxidants. The effect of various concentrations (1 to 200 microg/mL blood) of CRP on the generation of oxygen radicals by neutrophils was measured as luminol-dependent chemiluminescence (chemiluminescent activity) on a luminometer (Auto Lumat LB953, EG & G Berthold, Gaithersburg, MD). The unit of chemiluminescent activity is the relative light unit and was expressed as relative light unit/white blood cell (RLU/WBC). Chemiluminescent activity of blood without CRP was slightly higher than that of buffer with or without CRP. CRP markedly increased the chemiluminescent activity of blood. There was no significant change in the chemiluminescent activity of WBCs with 1 microg/mL of CRP. The chemiluminescent activity increased significantly with higher concentrations of CRP. The percent increases in the chemiluminescent activity with 2, 5, 10, 25, 50, 100 and 200 microg/mL of CRP were 45%, 72%, 50%, 70%, 52%, 67%, and 68% respectively. Antioxidants (superoxide dismutase, catalase, and dimethylthiourea) blocked CRP-induced oxygen radicals by WBCs. These results suggest that CRP increases the generation of oxygen radicals from the WBCs. CRP-induced atherosclerosis may be mediated through generation of oxygen radicals by neutrophils.

Animals↗

PubMed2003

Effects of flaxseed oil on serum lipids and atherosclerosis in hypercholesterolemic rabbits.

OBJECTIVE: Flaxseed oil has very high content of alpha-linolenic acid (C18:3n-3, omega-3 [n-3] fatty acid). Based on the usefulness of n-3 fatty acid in fish oil against cardiovascular diseases, flaxseed oil is marketed as a health food. The n-3 fatty acid in flaxseed oil is different than that of fish oil. Indirect evidence suggests that the omega-3 fatty acid in flaxseed oil is not effective in lowering serum lipids and hypercholesterolemic atherosclerosis. The effects of flaxseed oil on serum lipids and hypercholesterolemic atherosclerosis are not known. An investigation, therefore, was made of flaxseed oil on high-cholesterol diet-induced atherosclerosis, serum lipids (triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, risk ratio of total cholesterol to high-density lipoprotein cholesterol), serum and aortic malondialdehyde, an index of levels of reactive oxygen species, aortic chemiluminescence (a measure of antioxidant reserve), and reactive oxygen species-producing activity of white blood cell chemiluminescence in rabbits. METHODS: The rabbits were assigned to four groups: Group I, regular diet (control); Group II, 5% flaxseed oil in regular diet; Group III, 0.5% cholesterol diet; Group IV, diet containing 0.5% cholesterol and 5% flaxseed oil. Blood samples were collected before and after 4 and 8 weeks of experimental diets for measurement of serum lipids, serum malondialdehyde, and white blood cell chemiluminescence. At the end of 8 weeks of the experimental diet, aortas were removed for measurement of atherosclerotic plaques, aortic malondialdehyde, and antioxidant reserve. RESULTS: Serum total cholesterol, triglycerides, and low-density and high-density lipoprotein cholesterol, and risk ratio of total cholesterol to high-density lipoprotein cholesterol, were elevated to a similar extent in Groups III and IV compared to Groups I and II. The extent of atherosclerosis in Groups III and IV was similar (56.74% +/- 11.14% vs 58.01% +/- 10.95%). Groups III and IV both had similar increases in serum and aortic malondialdehyde and antioxidant reserve. Reactive oxygen species-producing activity of white blood cells increased in Group III, and flaxseed oil prevented the cholesterol-induced increase in white blood cell chemiluminescence in Group IV. CONCLUSION: These results suggest that flaxseed oil does not produce an alteration in serum lipids or in the extent of hypercholesterolemic atherosclerosis; however, it decreases white blood cell chemiluminescence. The ineffectiveness of flaxseed oil was associated with its ineffectiveness in altering the levels of oxidative stress.

Animals↗

PubMed2003

Elevated levels of plasma homocysteine in hypertensive patients with diabetes mellitus.

BACKGROUND: Homocysteine generates oxygen radicals (superoxide anion and hydrogen peroxide) that are known to produce vasoconstriction. Hypertension is a common problem in individuals with diabetes mellitus. It is possible that hypertension in diabetic patients may be due to increased levels of plasma homocysteine. We investigated the plasma levels of homocysteine, factors involved in homocysteine metabolism (serum folic acid and vitamin B12) and lipid peroxidation product in the serum of diabetic patients with hypertension. METHODS AND RESULTS: The studies were conducted in three groups: 1) healthy controls, and diabetic patients who were 2) normotensive and 3) hypertensive. Plasma homocysteine, serum malondialdehyde (a lipid peroxidation product), vitamin B12, and folic acid were measured in these patients. Plasma homocysteine and serum malondialdehyde levels were elevated in diabetic patients compared to the control group. Plasma levels of homocysteine and serum levels of malondialdehyde were higher in the hypertensive diabetic patients than in those who were normotensive. Levels of serum folate were lower in hypertensive diabetic patients compared to the normotensive group. Levels of serum vitamin B12 were similar in both the normotensive and hypertensive diabetic patients. CONCLUSIONS: Levels of plasma homocysteine and serum malondialdehyde are elevated in hypertensive diabetic patients. Hyperhomocysteinemia may be involved in the induction and sustaining of hypertension in diabetic patients.

Adult↗

PubMed2003

Suppression of oxidative stress as a mechanism of reduction of hypercholesterolemic atherosclerosis by aspirin.

BACKGROUND: Hypercholesterolemia increases the formation of arachidonic acid and thereby synthesis of prostaglandins and leukotrienes. During synthesis of these eicosanoids, oxyradicals are produced. Oxyradicals have been implicated in the development of hypercholes-terolemic atherosclerosis. Aspirin, an inhibitor of synthesis of prostaglandins, would prevent the generation of oxyradicals and hence would prevent the development of atherosclerosis. The purpose of the investigation was to determine if aspirin attenuates the development of hypercholesterolemic atherosclerosis, and if this attenuation is associated with a decrease in the oxidative stress. METHODS AND RESULTS: Three groups of rabbits were used for this study: Group I, control; Group II, 0.5% cholesterol; Group III, 0.5% cholesterol plus 0.068% aspirin. Blood samples were collected before and after 1 and 2 months of experimental diets for measurement of serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, serum malondialdehyde, and white blood cell chemiluminescence, a measure of oxyradicals produced by white blood cells. Aortas were removed at the end of the protocol for the measurement of atherosclerotic plaques, malondialdehyde and aortic chemiluminescence, a measure of antioxidant reserve. Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and ratio of total cholesterol to high-density lipoprotein cholesterol increased to a similar extent in Groups II and III compared to Group I. Serum triglycerides increased in both Groups II and III; however, the increase was greater in Group III than in Group II. Levels of serum and aortic malondialdehyde, and white blood cell-chemiluminescence were higher in Group II compared to Group I. Aspirin decreased the levels of these parameters. Antioxidant reserve increased in both Groups II and III, the increase being greater in the latter than the former. White blood cell-chemiluminescence increased in Group II compared to Group I, but remained unaltered in Group III compared to Group I. Aspirin treatment reduced the development of atherosclerosis by approximately 47%. CONCLUSION: These results suggest that aspirin, an inhibitor of cyclooxygenase, reduced the development of hypercholesterolemic atherosclerosis, and this effect was associated with a decrease in the oxidative stress.

Animals↗

PubMed2002

Relaxant effect of oxygen free radicals on rabbit tracheal smooth muscle.

We investigated the effect of exogenously generated superoxide anions (O(2)(-)), hydrogen peroxide (H(2)O(2)) and hydroxyl radicals (.OH) on isolated rabbit tracheal smooth muscle suspended in Krebs-Ringer solution. The ability of oxygen free radicals (OFRs) to affect acetyicholine (Ach)-induced contraction in these muscles was also investigated. OFRs, in general, produced a concentration-dependent relaxation of the tracheal smooth muscle in the doses used. However, in large concentrations, O(2)(-) and H(2)O(2) produced effects which were smaller than those obtained with lower concentrations. The relaxant effects of these oxyradicals were progressive and lasted throughout the 20min observation period. At all concentrations used, the OFRs tended to abolish or reduce Ach-induced contraction in a concentration-dependent manner. O(2)(-) was more potent than H(2)O(2) or DHF in relaxing the Ach-precontracted muscle and in inhibiting the response of the muscle to Ach. OFR-induced relaxation of the Ach-contracted muscle was not due to inactivation of the Ach by OFRs. Relaxation produced by OFRs was greater in preparations with intact epithelium than in those denuded of epithelium. The relaxant effects were blocked by indomethacin, a cyclooxygenase inhibitor. OFRs in the presence of indomethacin produced contraction only in the preparations with intact epithelium, suggesting a release of contractile factor(s) from epithelium. These results suggest that OFRs relax rabbit tracheal smooth muscle. The relaxation appears to be mediated through the synthesis and release of prostaglandins from the epithelium and smooth muscles.

Analysis of Variance↗

PubMed2002

Hyperhomocysteinemia and venous thrombosis.

Deep vein thrombosis (DVT) leads to venous ulcers in later life. Venous ulcers are the majority of chronic lower extremity wounds. Recent evidence suggests that hyperhomocysteinemia is an independent risk factor for venous thrombosis. Other evidence suggests that dietary supplementation with folic acids and vitamins helps to change hyperhomocysteinemia. This may be the key to wound management in future.

Journal Article↗