Magadi Gopalakrishna Sridhar

Antioxidants preserve redox balance and inhibit c-Jun-N-terminal kinase pathway while improving insulin signaling in fat-fed rats: evidence for the role of oxidative stress on IRS-1 serine phosphorylation and insulin resistance

The oxidative stress-sensitive c-Jun-N-terminal kinase (JNK) pathway is known to be activated in diabetic condition and is involved in the progression of insulin resistance. However, the effect of antioxidants on JNK pathway and insulin resistance has not been investigated. The present study was aimed to investigate the effect of antioxidants on redox balance, insulin sensitivity, and JNK pathway in high-fat-fed rats. Male Wistar rats were divided into four groups: the control group - received a rodent chow; control+antioxidant group - fed with rodent chow supplemented with 0.2% (w/w) vitamin E, 0.3% (w/w) vitamin C, and 0.5% (w/w) alpha-lipoic acid; high-fat group - received high-fat diet; and high fat+antioxidant group - fed with high-fat diet supplemented with above antioxidants. Fat feeding to rats for 9 weeks significantly increased IRS-1 serine phoshorylation, reduced insulin-stimulated IRS-1 tyrosine phosphorylation and insulin sensitivity. High-fat diet also impaired redox balance and activated the redox-sensitive serine kinase - JNK pathway. Antioxidant supplementation along with high-fat diet preserved the free radical defense system, inhibited the activation of JNK pathway, and improved insulin signaling and insulin sensitivity. The present study shows for the first time that antioxidants inhibit JNK pathway and IRS-1 serine phosphorylation while improving insulin sensitivity in fat-fed rats. These findings implicate the beneficial effect of antioxidants in obesity-/dyslipidemia-induced insulin resistance in humans.

Increased Glycation of Hemoglobin in Chronic Renal Failure Patients and Its Potential Role of Oxidative Stress

Among the various mechanisms proposed, the process of non-enzymatic glycation of proteins is believed to play an important role in the pathogenesis of chronic complications associated with renal failure. The two traditional factors found to modulate the early glycation of proteins are the prevailing concentration of glucose and half life of the protein. Among the various proteins that are known to undergo nonenzymatic glycation in vivo, hemoglobin has been the most thoroughly investigated. Determination of glycated hemoglobin in diabetic patients is currently acknowledged as the most reliable indicator for assessment of retrospective glycemic control and the planning of clinical management. The clinical utility of glycated hemoglobin measurements, however, in renal failure is controversial, given the numerous earlier studies showing no correlation between glycated hemoglobin and other indicators of blood glucose control in uremic subjects. With few exceptions, previous studies have suggested that the concentration of glycated hemoglobin was increased in uremic patients. There is documented evidence that increased glycated hemoglobin levels are found in certain non-diabetic states. So it stands to reason that hyperglycemia, although clearly being the culprit in diabetes, does not provide the complete answer to the etiology of increased early glycated products in non-diabetic conditions including chronic renal failure. This article reviews available evidence supporting increased glycation of hemoglobin in patients with chronic renal failure. Potential mechanisms for this increase are examined with special emphasis on the potential role of oxidative stress.

Cardiac enzyme levels in myocardial dysfunction in newborns with perinatal asphyxia

ObjectiveTo study the usefulness of cardiac enzymes in evaluating myocardial damage in perinatal asphyxia.MethodsThirty term babies with perinatal asphyxia and without any congenital malformations were selected as cases. They were compared with thirty healthy term babies without asphyxia. Myocardial dysfunction was evaluated using clinical, electrocardiography, echocardiography and cardiac enzymes i.e, troponin-T and CK-MB levels.ResultsAmong the 30 cases 23 had evidence of myocardial involvement while one baby in the control group had ECG evidence compatible with cardiac involvement. Cardiac enzymes were significantly increased in babies with perinatal asphyxia. The mean level of C-troponin-T among cases and controls were 0.22±0.28 and 0.003±0.018 while CK-MB levels were 121±77.4 IU/L and 28.8 ± 20.2 IU/L respectively. C-troponin-T had higher sensitivity and specificity compared to CK-MB levels. Moreover, C troponin-T levels correlated well with severity and outcome in babies with perinatal asphyxia.ConclusionC-Tropopnin assay is useful in evaluating the severity of myocardial damage and outcome in perinatal asphyxia.

Curcumin prevents inflammatory response, oxidative stress and insulin resistance in high fructose fed male Wistar rats: Potential role of serine kinases.

Emerging evidence suggests that high fructose consumption may be a potentially important factor responsible for the rising incidence of insulin resistance and diabetes worldwide. The present study investigated the preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high fructose fed male Wistar rats at the molecular level. Fructose feeding for 10 weeks caused oxidative stress, inflammation and insulin resistance. Curcumin treatment attenuated the insulin resistance by decreasing IRS-1 serine phosphorylation and increasing IRS-1 tyrosine phosphorylation in the skeletal muscle of high fructose fed rats. It also attenuated hyperinsulinemia, glucose intolerance and HOMA-IR level. Curcumin administration lowered tumor necrosis factor alpha (TNF-α), C reactive protein (CRP) levels and downregulated the protein expression of cyclo-oxygenase 2 (COX-2), protein kinase theta (PKCθ). In addition, inhibitor κB alpha (IκBα) degradation was prevented by curcumin supplementation. Treatment with curcumin inhibited the rise of malondialdehyde (MDA), total oxidant status (TOS) and suppressed the protein expression of extracellular kinase ½ (ERK ½), p38 in the skeletal muscle of fructose fed rats. Further, it enhanced Glutathione Peroxidase (GPx) activity in the muscle of fructose fed rats. At the molecular level, curcumin inhibited the activation of stress sensitive kinases and inflammatory cascades. Our findings conclude that curcumin attenuated glucose intolerance and insulin resistance through its antioxidant and anti-inflammatory effects. Thus, we suggest the use of curcumin as a therapeutic adjuvant in the management of diabetes, obesity and their associated complications.

Amelioration of oxidative stress and insulin resistance by soy isoflavones (from Glycine max) in ovariectomized Wistar rats fed with high fat diet: The molecular mechanisms

Estrogen deficiency after menopause accelerates the redox imbalance and insulin signaling, leading to oxidative stress (OS) and insulin resistance (IR). The molecular mechanisms by which the loss of ovarian hormone leads to OS and IR remain unclear. In the present study we found that rats when subjected to ovariectomy (OVX) resulted in reduction of whole blood antioxidants and elevation of oxidant markers. The expression of anti-oxidant enzymes, superoxide dismutase (SOD1) and glutathione peroxidase (GPX1) was suppressed whereas the pro-oxidative enzyme NADPH oxidase (NOX4) and mitogen activated protein (MAP) kinases ERK 1/2 and p38 were increased at different tissues. Treatment with soy (SIF, 150 mg/kg BW for 12 weeks) extract markedly reversed these metabolic changes and improved OS. Ovariectomized rats also displayed glucose intolerance (GI) and IR as evident from the impaired glucose tolerance test, and reduced expression of adipose and hepatic insulin receptor beta (IRβ) and adipose tissue GLUT4. Treatment with SIF reversed the ovariectomy induced GI and IR. On the other hand, all these metabolic changes were further augmented when ovariectomy was followed by a high fat diet, and these changes were also reversed by SIF. Taken together, these findings emphasized the antioxidant property and anti-diabetic effects of soy isoflavones suggesting the use of this natural phytoestrogen as a strategy for relieving oxidative stress and insulin resistance in postmenopausal women.

Formulation of questions followed by small group discussion as a revision exercise at the end of a teaching module in biochemistry

Undergraduate medical students get fewer opportunities to clarify their doubts and to reinforce their understanding of concepts after lecture classes. There is no information available in the literature that addresses the question of usefulness of prior formulation of questions followed by small group discussion by undergraduate medical students as a revision exercise. The purpose of this work is to evaluate the effect of formulation of objective type short answer questions by undergraduate medical students followed by small group discussion on the answers of the questions prepared as a revision exercise on their understanding of the topic “amino acid metabolism” and the retention of the gain after 15 days. At the end of a regular teaching module on the topic of amino acid metabolism, undergraduate medical students were asked to prepare 16 objective type short answer questions on the various aspects of the topic as homework. Small group discussions involving 12–14 students in each group and lasting one hour were conducted on the questions and answers prepared by them in the presence of a faculty member. The effects on low, medium, and high achievers were evaluated with multiple choice questions by pre‐test and post‐tests before and after the group discussion. Formulation of questions was highly effective in improving understanding on the topic for all the students. The overall mean post‐test scores after the formulation of questions (12.6) and after the small group discussion that followed (14.7) were significantly higher than the mean pre‐test score (8.5). For high achievers, the gain from formulation of questions was higher than the gain from small group discussion. Small group discussion was highly effective for all students. The gain from small group discussion was higher among the low and medium achievers in comparison with the high achievers. The gain from the exercise was retained among the low, medium, and high achievers after 15 days. In conclusion, formulation of short answer questions followed by small group discussion on the answers of the questions prepared by the undergraduate medical students is an effective revision exercise for improving their understanding on a selected topic.

Protective Effect of Soy Isoflavones (from Glycine max) on Adipose TissueOxidative Stress and Inflammatory Response in an Experimental Model ofPost-menopausal Obesity: The Molecular Mechanisms

Obesity, adiposity mediated oxidative stress and inflammatory response has been identified to have an etiological origin for most of the complications associated with ageing populace. However, there are limited studies addressing the metabolic role of adipose tissue in the pathobiology of postmenopausal complications with respect to oxidative stress and inflammation. Numerous studies have reported the beneficial effects of soy isoflavones on postmenopausal complications; however, its efficacy these complications in postmenopausal model of obesity remain unclear. In the present study we found that the both ovariectomy and high fat diet (30 per cent fat) in isolation and in combination developed adipose tissue oxidative stress as evidenced by the reduced level of total antioxidant status (TAS) in association with elevated levels of adipose tissue malondialdehyde (MDA) and MDA/TAS ratio. These rats also displayed with inflammation as showed by increased levels of plasma tumor necrosis factor alpha (TNFα) and high sensitive C – reactive protein (hsCRP). The expression of adipose tissue inflammatory proteins; cyclo-oxygenase 2 (COX2), monocyte chemo attractant protein (MCP1) and protein kinase C alpha (PKCα) were heightened in response to both ovariectomy and high fat diet. All these metabolic changes were further augmented when ovariectomy was followed by high fat diet. This suggests that there was a synergism between the postmenopausal state and intake of fat rich diet in the development of adipose tissue oxidative stress and inflammatory response. Treatment with soy isoflavones significantly inhibited these metabolic changes improved adipose tissue oxidative stress and inflammatory response suggesting the use of this natural phytoestrogen as an anti-oxidant and anti-inflammatory agent for relieving metabolic consequences associated with postmenopausal women.

Electrocardiographic and echocardiographic changes in perinatal asphyxia

ObjectiveTo study the usefulness of cardiac enzymes in evaluating myocardial damage in perinatal asphyxia.MethodsThirty term babies with perinatal asphyxia and without any congenital malformations were selected as cases. They were compared with thirty healthy term babies without asphyxia. Myocardial dysfunction was evaluated using clinical, electrocardiography, echocardiography and cardiac enzymes i.e, troponin-T and CK-MB levels.ResultsAmong the 30 cases 23 had evidence of myocardial involvement while one baby in the control group had ECG evidence compatible with cardiac involvement. Cardiac enzymes were significantly increased in babies with perinatal asphyxia. The mean level of C-troponin-T among cases and controls were 0.22±0.28 and 0.003±0.018 while CK-MB levels were 121±77.4 IU/L and 28.8 ± 20.2 IU/L respectively. C-troponin-T had higher sensitivity and specificity compared to CK-MB levels. Moreover, C troponin-T levels correlated well with severity and outcome in babies with perinatal asphyxia.ConclusionC-Tropopnin assay is useful in evaluating the severity of myocardial damage and outcome in perinatal asphyxia.

Curcumin inhibits hyperlipidemia and hepatic fat accumulation in high-fructose-fed male Wistar rats

Abstract Context: Curcumin, an active principal of Curcuma longa Linn. (Zingiberaceae), has potent antioxidant and anti-inflammatory properties. Objectives: This study investigated the effects of curcumin on hyperlipidemia and hepatic steatosis in high-fructose-fed Wistar rats. Materials and methods: Forty male Wistar rats were divided into four groups with 10 rats in each. Two groups were fed with standard rodent diet and the other two with 60% high-fructose diet for 10 weeks. Curcumin (200 mg/kg body weight) was administered along with the diets simultaneously to each of the aforementioned diet groups. After 10 weeks of experiment, blood samples were collected from tail vein. Liver, adipose and epididymal tissues were collected after sacrifice of the animals and stored for further analyses. Results: Administration of curcumin reduced body weight (280.6 ± 7.4 g), liver weight (2.5 ± 0.2 g/100 g BW), adipose weight (1.4 ± 0.3 g/100 g BW), plasma levels of TAG (86.1 ± 13.5 mg/dL), VLDL-C (17.2 ± 2.7 mg/dL), lipid ratios and increased HDL-C (28.4 ± 4.5 mg/dL) in fructose-fed rats. Curcumin supplementation significantly lowered TAG content and decreased the protein expression of LXR-α (43%) and SREBP1c (59%) in the liver. Furthermore, curcumin suppressed the expression of lipogenic enzymes, ACLY (95%), ACC (50%) and FAS (77%) in rats fed with high-fructose diet. No significant change was found in the expression of PPAR-α. Discussion and conclusion: Curcumin prevented the high-fructose induced hyperlipidemia and hepatic steatosis.

A Randomized Controlled Trial to Study the Effect of Yoga Therapy on Cardiac Function and N Terminal Pro BNP in Heart Failure

AIMS The purpose of this study was to evaluate whether yoga training in addition to standard medical therapy can improve cardiac function and reduce N terminal pro B-type natriuretic peptide (NT pro BNP) in heart failure (HF). METHODS 130 patients were recruited and randomized into two groups: Control Group (CG) (n = 65), Yoga Group (YG). In YG, 44 patients and in CG, 48 patients completed the study. Cardiac function using left ventricular ejection fraction (LVEF), myocardial performance index (Tei index), and NT pro BNP, a biomarker of HF, was assessed at baseline and after 12 weeks. RESULT Improvement in LVEF, Tei index, and NT pro BNP were statistically significant in both the groups. Furthermore, when the changes in before and after 12 weeks were in percentage, LVEF increased 36.88% in the YG and 16.9% in the CG, Tei index was reduced 27.87% in the YG and 2.79% in the CG, NT pro BNP was reduced 63.75% in the YG and 10.77% in the CG. The between group comparisons from pre to post 12 weeks were significant for YG improvements (LVEF, P < 0.01, Tei index, P < 0.01, NT pro BNP, P < 0.01). CONCLUSION These results indicate that the addition of yoga therapy to standard medical therapy for HF patients has a markedly better effect on cardiac function and reduced myocardial stress measured using NT pro BNP in patients with stable HF.