Inhibitory effect of metalloporphyrins in conjunction with cholesterol on hepatic phospholipase A2 activityin vivo in rats

We investigated the effect of cholesterol and the metalloporphyrins cobalt mesoporphyrin (CoMP) and chromium protoporphyrin (CrPP) on phospholipase A₂ (PLA₂) activity and the consequent hepatic mitochondrial stability as well as on lipid concentrations. Our studies revealed that on administration of cholesterol, CrPP, CoMP as well as simultaneous adminstration of cholesterol and CrPP, there was an inhibition of PLA₂ activity. These moieties may therefore, be agents for preventing destabilisation of the mitochondrial membrane and the consequent pathological conditions which may arise due to membrane lysis. Our results revealed that cholesterol administration increased phospholipid concentration, albeit by modest amounts. Although the independent administration of metalloporphyrins led only to minor elevations in phospholipid concentration, the simultaneous administration of cholesterol and CrPP generated a steep elevation in the concentration of total phospholipid. Since cholesterol inhibits PLA₂ activity it has the potential of being therapeutic agent for preventing the pathological conditions which may arise due to membrane lysis.     

Moderately high altitude habitation modulates lipid profile and alkaline phosphatase activity in aged <Emphasis Type="Italic">Khasis</Emphasis> of Meghalaya

The indigenous Khasis inhabit different geographical and climatic locations of Meghalaya. In this study, we intended to find out whether habitation in moderately high altitude place has any effect on the lipid and liver profile amongst the aged Khasis. The level of various serum parameters under lipid and liver profile were analyzed and compared from aged (65–70 years) male Khasi residents of moderately high (Shillong city) and low (Byrnihat) altitude places. Results obtained from the lipid profile data show decreased total serum cholesterol (29%), triglyceride (27%) and LDL-cholesterol (42%) level in the old Khasis of Shillong compared to Byrnihat. Furthermore, the alkaline phosphatase activity was significantly raised (47%) in the old Khasis from Shillong as against Byrnihat. The decreased level of total cholesterol, triglyceride and LDL-cholesterol in old Khasis from Shillong may be due to living and acclimatization in high altitude with low annual temperature. Moderately high elevation could have acted as a stressor, thereby reducing the level of serum cholesterol, triglyceride and LDL-cholesterol, which may put them at a lower risk of cardiovascular diseases. In comparison, old residents of Byrnihat with high cholesterol, triglyceride and LDL-cholesterol levels may elevate their risk of coronary complications. The raised alkaline phosphatase activity amongst the old Khasis of Shillong could be due to increased bone and/or intestinal turnover as a result of living in high altitude, which, however, may elevate the risk of osteoporosis. Taken together, we conclude that low cholesterol, triglyceride and LDL-cholesterol levels, accompanied with high alkaline phosphatase activity amongst the old Khasis of Shillong, could be due to the influence of high altitude and mild climatic conditions that prevails.     

Effect of ethanol on liver antioxidant defense systems: Adose dependent study

Alcohol induced oxidative stress is linked to the metabolism of ethanol. In this study it has been observed that administration of ethanol in lower concentration caused gain in body and liver weight. while higher concentration of ethanol caused lesser gain in body and liver weight. Ethanol treatment enhanced lipid peroxidation significantly, depletion in levels of hepatic glutathione and ascorbate, accompanied by a decline in the activities of glutathione peroxidase and glutathione reductase, and increased in hepatic glutathione s-transferase activity. Interestingly catalase activity increases in lower concentration of ethanol exposure, and decreased in higher concentration. Superoxide dismutase activity was also increased on ethanol exposure. But, ethanol feeding did not show any effect on glucose-6-phosphate dehydrogenase activity. Ethanol ingestion perturbs the antioxidant system in a dose and time dependent manner.     

Evidence for oxidative stress in osteoarthritis

Evidence of increased oxidative stress in patients of osteoarthritis in comparison with healthy control subjects was investigated by measuring the thiobarbituric acid reactive substances (TBARS), vitamin C, reduced glutathione (GSH) and the activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in erythrocytes. It was observed that osteoarthritis patients were more susceptible to oxidative damage than controls as evident from increased TBARS and decreased ascorbic acid, GSH, catalase and GPx in erythrocytes. Significant increase in SOD activity found in patients might be an adaptive response. With the understanding of the role of antioxidants in arthritis, it is becoming increasingly clear that these agents seem to be beneficial in osteoarthritis.     

Preliminary studies on serum lipids, apolipoprotein-B and oxidative stress in xanthelasma

Serum lipid profile, apolipoprotein-B (apo-B), malondialdehyde levels(MDA) and superoxide dismutase (SOD) activity were assessed in 12 cases of xanthelasma with and without coronary artery disease (CAD)/hypertension (HTN) and results are compared with healthy controls. Dyslipidemia was found in 65% cases of xanthelasma as compared to 20% healthy controls. Xanthelasma patients had significantly high malondialdehyde (MDA) levels (p<0.01) and significantly decreased (p<0.05) SOD activity as compared to controls. Among xanthelasma patients, xanthelasma with CAD/HTN showed higher total cholesterol (236±32.7 vs 188±24.7 mg/dl), low density lipoprotein cholesterol (157±35.5 vs 113±16 mg/dl) and Apo-B (120.5±9.4 vs 114±19.2 mg/dl) levels as compared to xanthelasma without CAD/HTN. Results of our study indicate that xanthelasma patients with increased apo-B, MDA and decreased SOD need cardiovascular monitoring.     

Serum lipid profile and lipoprotein lipase activity in patients of ischaemic heart disease

Total lipids, cholesterol, phospholipids, free fatty acids, total glycerides and lipoprotein lipase (LPL) activity of 26 patients of Ischaemic Heart Disease (IHD) and similar number of age and sex matched control individuals were studied to find out abnormality in lipid metabolism. Incidence of IHD was more common amongst males as compared to females. Significant low levels of serum LPL activity and higher levels of other parameters was thus evident in patients of IHD and this may explain the altered lipid metabolism and hypertriglyceridemia in patients of IHD.     

Oxidative injury and antioxidant vitamins E and C in Schizophrenia

Susceptibility of Schizophrenic patients to lipid peroxidation relative to healthy control subjects was investigated by measuring the malondialdehyde (MDA) levels in plasma. The main finding was that Schizophrenic patients were more susceptible than control subjects to oxidative damage as evident from increased MDA levels in plasma. Antioxidant levels are also depleted in Schizophrenic patients when compared to normal subjects as evident from decreased levels of vitamins E and C in the plasma. Impaired antioxidant defense and increased lipid peroxidation suggests that treatment with antioxidants (Vitamin E, Vitamin C, beta carotene) at the initial stages of illness may prevent further oxidative injury and deterioration of associated neurological deficits in Schizophrenia.     

Phospholipid and cholesterol levels in serum and bile in cholelithiasis

Cholesterol and phospholipids were estimated in serum and bile from hepatic duct and gallbladder of twenty five patients of gallstone with functioning gallbladder (Group-I) and an equal number of patients having diseases other than of hepatobiliary system acting as control (Group-II). Group-I patients showed high serum cholesterol and low serum phospholipid levels as compared to those of Group-II. Cholesterol levels in hepatic duct and gallbladder bile were higher in Group-I than in Group-II whereas the phospholipid levels in the bile of Group-I were lower than in Group-II. The phospholipid: cholesterol ratios in hepatic duct and gallbladder bile of Group-I were 2.76 and 3.03 respectively as compared to 5.62 and 5.92 in Group-II.     

Differential Expressions of p53, p53R2, hRRM2 and PBR in Chronic Lymphocytic Leukemia: A Correlation with Intracellular Cholesterol

Regulation of intracellular cholesterol homeostasis exists under balance between intracellular biosynthesis and uptake from extracellular origin by cell surface transport proteins. Expected role of cholesterol on either tumor suppressor gene and/or DNA synthesis has been aimed in the present study to explore intracellular cholesterol homeostasis in CLL subjects. Higher expressions of p53R2 (p53 dependent subunit of ribonucleotide reductase) and p53 were found in lymphocytes of chronic human lymphocytic leukemia as comparison to their normal counterparts. Inverse relation was found with p53 independent R2 subunit (in human hRRM2) of ribonucleotide reductase, which was found to be decreased from its control group. More expression of peripheral type benzodiazepine receptor, a cholesterol transporter, was noticed in isolated nuclear fraction with simultaneous increase of cholesterol concentration in cytoplasmic and nuclear compartments. A parallel increase of cholesterol in cell nucleus with increased p53R2 expression shows priority of the involvement of cholesterol in the process of cell replication.     

Cholesterol synthesis and its regulation in acute myocardial infarction

Cholesterol synthesis and its suppression by LDL was measured in freshly isolated leucocytes from patients with acute myocardial infarction and healthy controls. Cells incubated for different time intervals in lipoprotein-deficient serum exhibited increased cholesterol synthesis. The magnitude of this increase was far greater in leucocytes of hyperlipemic patients than in normolipemic patients. Addition of LDL to the incubation medium produced suppression of cholesterol synthesis. This reduction was less in hyperlipemic patients as compared to normolipemic patients. These observations may imply reduced suppression of HMG-CoA reductase activity with high endogenous cholesterol synthesis in patients suffering with acute myocardial infarction.     

Studies on the effect of monosodium glutamate (MSG) administration on the activity of xanthine oxidase, superoxide dismutase and catalase in hepatic tissue of adult male mice

Subcutaneous administration of monosodium glutamate (MSG), to normal adult male mice, for six consecutive days at dose levels of 4 and 8 mg/g body weight, significantly increased the level of free radical initiating enzyme, xanthine oxidase, whereas the activity of free radical scavenging enzymes, like catalase and superoxide dismutase was significantly decreased in hepatic tissue. These observations suggested that ingestion of MSG at dose level of 4 mg/g body weight and above, induced oxidative stress in the hepatic tissue of adult male mice.     

Study of lipid peroxide and lipid profile in diabetes mellitus

The study was designed to find out the correlation between lipid peroxidation, lipoprotein levels to severity and complication of diabetes mellitus. Degree of lipid peroxidation was measured in terms of malondialdehyde (MDA) along with lipid profile and blood glucose in diabetes mellitus. It is categorised into insulin dependent diabetes mellitus (IDDM), non insulin dependent diabetes mellitus (NIDDM) and diabetes mellitus(DM) with complication. Total 112 known diabetic patients and 52 non-diabetic controls were studied. These patients were grouped as per the concentration of fasting blood glucose level i.e. controlled, poorly controlled, and uncontrolled group. There are significant increase in the lipid peroxide (MDA) and lipid profile except HDL cholesterol which is decreased, has been found in all groups as compared to controls In NIDDM group lipid peroxidation was markedly increased than IDDM group and it was higher in DM with complications. Other finding observed was that the level of lipid peroxide increased as per the increase in concentration of blood glucose. The increase lipid peroxidation in the hyperglycemic condition may be explained, as the superoxide dismutase enzyme which is antioxidant becomes inactive due the formation of superoxide radical within the cell. Maximum lipid peroxidation leads to the damage of the tissue and organs which results into complication in diabetic patients. High levels of total cholesterol appear due to increased cholesterol synthesis. The triglyceride levels changes according to the glycemic, control. The increase may be due to overproduction of VLDL-TG. It is concluded that good metabolic control of hyperglycemia will prevent in alteration in peroxidation and the lipid metabolism, which may help in good prognosis and preventing manifestation of vascular and secondary complication in diabetes mellitus.     

Hypolipidemic Effect of <Emphasis Type="Italic">Celastrus paniculatus</Emphasis> in Experimentally Induced Hypercholesterolemic Wistar Rats

The objective of the present study was to evaluate hypolipidemic effect of methanolic extract of Celastrus paniculatus in experimentally induced hypercholesterolemic rats. Hypercholesterolemia was induced by feeding the animals with high fat diet. Oral administration of methanolic seed extract (50%) of Celastrus paniculatus at the optimized dose of 65 mg/kg body weight, substantially reduced the plasma total cholesterol, triglycerides and LDL cholesterol in comparison with induced hypercholesterolemic animal group and the results were comparable with the standard hypocholesterolemic drug and almost similar to the control group. Atherogenic index and liver weight of treated animals also showed significant decrease compared to the hypercholesterolemic animals. It substantially increased the HDL cholesterol level as compared to control group. A significant increase in the activities of lipoprotein lipase and plasma LCAT enhanced hepatic bile acid synthesis and thereby, increased degradation of cholesterol to neutral sterols. Furthermore, the activities of HMG-CoA reductase, glucose 6-phosphate dehydrogenase and malate dehydrogenase were significantly reduced. Histological studies showed less cholesterol deposits in the aorta of animals fed with seed extract of C. paniculatus compared to the induced hypercholesterolemic animals not given C. paniculatus supplement.     

Anti-Atherosclerotic and Anti-Inflammatory Effects of Curcumin on Hypercholesterolemic Male Rabbits

Curcumin has a potent antioxidant and anti-inflammatory properties that may suppress inflammatory component of atherosclerosis. It has been demonstrated that curcumin derivatives can reduce the formation of arterial fatty streaks in cholesterol-fed rabbits. Therefore in this study we evaluated the protective effects of Curcumin on the progression of atherosclerosis. 20 mature rabbits were included for this study; they were randomly divided into four groups each of 5. Group 1: (normal control) were fed corn pellets diet and tab water, group 2: (high cholesterol diet control) were kept on cholesterol rich diet (2% cholesterol) and tab water. Group 3: (cholesterol and rosuvastatin treated group) were kept on cholesterol rich diet (2% cholesterol) and 2.5 mg/kg/day Rosuvastatin dispersed in DW and given orally, group 4: (cholesterol and curcumin treated group) were kept on cholesterol rich diet (2% cholesterol) and 0.2% curcumin added with corn pellets. The study continued for 12 weeks then assessment of serum level of high sensitive C-reactive protein, ICAM1, VCAM1 and PCSK9 was carried out at the end of the study. Total antioxidant activity of curcumin was also determined. Histopathological examination of aortic tissues for atherosclerotic changes was also carried out. Atherogenic (cholesterol rich diet) induced an increment in serum level of TC, LDL, VLDL and TG with concomitant decrement in serum level of HDL and increased atherogenic index. Treatment with curcumin produced substantial reduction in serum TC, LDL, TG with no effect on HDL level thus decreased atherogenic index. Rabbits treated with curcumin showed a significant reduction in the serum level of high sensitive C-reactive protein, ICAM1, VCAM, PCSK9 serum expression and aortic total antioxidant capacity. Curcumin has a potent anti-inflammatory and anti- oxidant effects against atherosclerosis so exerts a protective role by decreasing lipid oxidation and inflammatory markers.     

Immuno-Modulatory Effect and Therapeutic Potential of <Emphasis Type="Italic">Brugia malayi</Emphasis> Cystatin in Experimentally Induced Arthritis

Helminths are known to modulate host’s immune system and understanding this modulation can help in identification of novel therapeutic agents for autoimmune diseases. In this study, we have assessed the immune-modulatory activity and the therapeutic effect of Brugia malayi recombinant cystatin (rBmCys) in methylated BSA (mBSA) induced arthritis using rodent model. Administration of rBmCys has suppressed the severity of mBSA-arthritis in mastomys by reducing paw swelling and other clinical disease parameters as evident from significantly decreased arthritic index. The anti-arthritic effect of rBmCys was also confirmed by decreased histopathological score for synovitis, bone erosion and fibrosis in the tissue sections of paws. Further, this therapeutic effect of cystatin was found to be associated with significantly decreased production of IFN-γ and TNF-α and increased release of IL-4 and IL-10 cytokines. These results implied that rBmCys treatment has alleviated mBSA-induced arthritis and thus can be a promising alternative agent for the treatment of arthritis.     

Circadian Time Structure of Circulating Plasma Lipid Components in Healthy Indians of Different Age Groups

The circadian rhythm of human circulating lipid components was studied under nearnormal tropical conditions in 162 healthy volunteers (103 males and 59 females; 7 to 75 years of age). They followed a diurnal activity from about 06:00 to about 22:00 and nocturnal rest. These volunteers were divided into four groups: Group A (7–20 years), Group B (21–40 years), Group C (41–60 years) and Group D (61–75 years), comprising 42, 60, 35 and 25 participants, respectively. A marked circadian rhythm was demonstrated for each studied variable in each group by population-mean cosinor analysis (almost invariably p < 0.001). Furthermore, circadian rhythm characteristics were compared among the 4 groups by parameter tests and regressed as a function of age, separately for males and females. A second-order polynomial characterized the MESOR of HDL cholesterol, phospholipids and total lipids, as well as the 24-h amplitude of total cholesterol and phospholipids. The 24-h amplitude of total lipids decreased linearly with age. The 24-h acrophase of the oldest age group (Group D) was advanced in the case of total cholesterol, HDL cholesterol, and total lipids, whereas that of phospholipids was delayed. Mapping the circadian rhythm (an important component of the broader time structure or chronome, which includes a. o., trends with age and extra-circadian components) of lipid components is needed to explore their role in the aging process in health.     

Serum LCAT and lipoprotein—Transport cholesterol in hyperthyroid patients

The aim of the present study was to evaluate the serum levels of lecithin cholesterol acyl transferase and lipoprotein cholesterol in hyperthyroid patients. The serum levels of total cholesterol and triacylglycerols were also determined in order to assess the lipid status of these patients. It was observed that serum content of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density liproprotein cholesterol (HDL-C) were significantly lower (P<0.001) in these patients whereas serum triacylglycerols (Tg.) and very low density lipoprotein cholesterol (VLDL-C) (P>0.05) did not show any significant change as compared to control values. However, the serum level of lecithin cholesterol acyl transferase (LCAT) was significantly higher (P<0.001) in these patients. It is concluded that an increased LCAT activity plays a significant role in regulating lipoprotein cholesterol levels in hyperthyroid patients.     

Effect of Growth Hormone on Plasminogen Activator and Inhibitor Activity in Rat

Growth retardation is one of the significant changes in chronic kidney disease (CKD) and is associated with increased morbidity and mortality. Disturbances in growth hormone (GH) are held responsible for several complications in CKD. GH is a protein based peptide hormone which directly or indirectly regulates renal functions to ensure homeostasis. We investigated the effects of growth hormone on plasminogen activators (PA) in rat kidney, PA and plasminogen activator inhibitor (PAI), glucose and fibrinogen in plasma and serum lipid profile. Rats were injected daily with 250 mU GH kg-1 body weight subcutaneously for one week. Growth hormone treatment increased PA activity significantly in rat kidneys as compared to controls. No changes were seen in PA, PAI and fibrinogen levels in the plasma of two groups of rats. There was significant decrease in plasma glucose, total cholesterol and LDL-cholesterol levels in serum of treated group resulting in the decrease of HDL/LDL and total cholesterol/cholesterol ratios. However, triglycerides and VLDL showed significant higher activity in the serum of treated group as compared to controls. Our data suggests that GH administration might improve renal function by increasing PA activity in kidney as well as by reducing the cholesterol content in blood. GH may be effective in improving growth failure as it helps to maintain the normal homeostatic balance.     

Antioxidant Effect of Caffeic Acid on Oxytetracycline Induced Lipid Peroxidation in Albino Rats

Caffeic acid is a well-known phenolic compound widely present in plant kingdom. The aim of this study was to investigate the possible protective effect of caffeic acid (CA) against oxytetracycline (OXT) induced hepatotoxicity in male Albino Wistar rats. A total of 30 rats weighing 150–170 g were randomly divided into five groups of six rats in each group. Oral administration of OXT (200 mg/kg body weight/day) for 15 days produced hepatic damage as manifested by a significant increase in serum hepatic markers namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin and increased plasma and hepatic lipid peroxidation indices (TBARS and hydroperoxide). The present finding shows that the levels of enzymatic antioxidants namely superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were significantly decreased in OXT intoxicated rats. Upon oral administration of caffeic acid (40 mg/kg body weight/day) there were decreased hepatic marker activities, bilirubin and lipid peroxidation and increased enzymatic antioxidants in OXT + Caffeic acid group compared to Normal + OXT group(P < 0.05). Our study suggests that caffeic acid has antioxidant property and hepatoprotective ability against OXT induced toxicity.     

Hypolipidemic Activity of Cassia tora Seeds in Hyperlipidemic Rats

The hypolipidemic activity of Cassia tora (Chakvat, Chakunda) (Family: Caesalpiniaceae) seeds extract have been studied in two models of hyperlipidemia in rats. In an acute model, hyperlipidemia was induced by injecting a single dose of Triton WR-1339 (400 mg/kg, b.w.) intraperitonially in rats. Feeding with C. tora seed extract at the dose of 500 mg/kg, b.w. exerted significant lipid lowering effect as assessed by the reversal of plasma levels of total cholesterol, phospholipids, triglyceride and reactivation of post heparin lipolytic activity. In the chronic model, hyperlipidemia was induced by feeding with cholesterol rich-HFD in rats. The treatment with seeds extract of C. tora (500 mg/kg, b.w.) simultaneously for 15 days also caused lowering of lipid levels in plasma and liver following reactivation of plasma post heparin lipolytic activity and hepatic lipoprotein lipase activity in animals. The hypolipidemic activity of C. tora seeds was compared with a standard drug guggulipid (200 mg/kg, b.w.) in both models.