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Oral Metformin Treatment Prevents Enhanced Insulin Demand and Placental Dysfunction in the Pregnant Rat Fed a Fructose-Rich Diet  [PDF]
Ana Alzamendi,Hector Del Zotto,Daniel Castrogiovanni,Jose Romero,Andres Giovambattista,Eduardo Spinedi
ISRN Endocrinology , 2012, DOI: 10.5402/2012/757913
Abstract: The intake of a fructose-rich diet (FRD) in the normal female rat induces features similar to those observed in the human metabolic syndrome phenotype. We studied the impact of FRD administration to mothers on pregnancy outcome. On gestational day (Gd) zero rats were assigned to either group: ad libitum drinking tap water alone (normal diet, ND) or containing fructose (10% w/vol; FRD) through pregnancy; all rats were fed a Purina chow diet ad libitum ND and FRD rats were daily cotreated or not with metformin (60?mg/Kg/day oral; ND + MF and FRD + MF) and submitted to a high glucose load test on Gd 14. Additionally, placentas from different groups were studied on Gd 20. Data indicated that: (1) although FRD rats well tolerated glucose overload, their circulating levels of insulin were significantly higher than in ND rats; (2) the mesometrial triangle blood vessel area was significantly lower in placentas from FRD than ND dams; (3) the detrimental effects of FRD administration to mothers were ameliorated by metformin cotreatment. Our study suggests that excessive intake of fructose during pregnancy enhanced the risk for developing gestational diabetes and subsequent preeclampsia, and that metformin prevented the poor pregnancy outcome induced by FRD. 1. Introduction The prevalence of gestational diabetes mellitus (GDM) has significantly increased during the last decades [1], and offspring born to mothers with GDM present a significantly increased risk of developing obesity and type 2 diabetes mellitus (T2DM) [2, 3]. Maternal anthropometric factors (e.g., prepregnancy body weight (BW), adiposity weight gain during pregnancy) account for the variance in offspring BW and adiposity at birth [1, 4], and on other risk factors as well [5, 6]. However, maternal nutrition is a highly important conditioning factor of fetal growth. GDM is characterized by impaired glucose tolerance/decreased insulin sensitivity, and mothers with GDM have an increased risk of developing preeclampsia (PE) [7, 8]. Although the pathogenesis of PE still remains unclear, it is accepted that PE is an endothelial cell disorder associated with marked maternal and neonatal morbidity [9]. On the other hand, insulin effectiveness and angiogenesis [10–12] are key factors for the control of endothelial cell function. Consequently, the presence of decreased insulin sensitivity in the mother may enhance the defects in angiogenic function [13, 14], leading to an increased risk of PE. Maternal nutritional disturbances during critical developmental periods [15–17] are known to raise the offspring’s
Lipid peroxidation and antioxidants in hyperlipidemia and hypertension
MORIEL,PATRICIA; PLAVNIK,FRIDA L; ZANELLA,MARIA T; BERTOLAMI,MARCELO C; ABDALLA,DULCINEIA SP;
Biological Research , 2000, DOI: 10.4067/S0716-97602000000200010
Abstract: lipid peroxidation and lipid-derived oxidized products have been implicated in the pathogenesis of a variety of human diseases. to clarify the role of oxidative stress in essential hypertension and hypercholesterolemia the in vitro oxidative susceptibility of ldl, the antioxidant status and the lipid peroxide content of blood plasma were examined in hypercholesterolemic (hc), hypertensive (h), hypercholesterolemic/hypertensive (hh) and normolipidemic/normotensive subjects (n). plasma ascorbate and lipid-soluble antioxidants were lower, while ldl oxidizability, ce-ooh and tl-ooh were higher in h, hc, and hh groups than in the n group. no difference was observed among groups for pl-ooh and isoprostanes. in summary, the results show that: 1) lipid- and water-soluble antioxidants are lower in hypercholesterolemic and hypertensive patients as compared to normal subjects, whereas the lipid peroxide content and the ldl susceptibility to oxidation were higher; 2) total cholesterol, ldl-cholesterol, apob and ce-ooh were negatively correlated with the content of a-tocopherol; 3) there was a positive correlation between the content of lipid-soluble antioxidants and the resistance of ldl to oxidation; and 4) ce-ooh and tl-ooh were positively correlated with total cholesterol and ldl-cholesterol.
Lipid peroxidation and antioxidants in hyperlipidemia and hypertension  [cached]
PATRICIA MORIEL,FRIDA L PLAVNIK,MARIA T ZANELLA,MARCELO C BERTOLAMI
Biological Research , 2000,
Abstract: Lipid peroxidation and lipid-derived oxidized products have been implicated in the pathogenesis of a variety of human diseases. To clarify the role of oxidative stress in essential hypertension and hypercholesterolemia the in vitro oxidative susceptibility of LDL, the antioxidant status and the lipid peroxide content of blood plasma were examined in hypercholesterolemic (HC), hypertensive (H), hypercholesterolemic/hypertensive (HH) and normolipidemic/normotensive subjects (N). Plasma ascorbate and lipid-soluble antioxidants were lower, while LDL oxidizability, CE-OOH and TL-OOH were higher in H, HC, and HH groups than in the N group. No difference was observed among groups for PL-OOH and isoprostanes. In summary, the results show that: 1) lipid- and water-soluble antioxidants are lower in hypercholesterolemic and hypertensive patients as compared to normal subjects, whereas the lipid peroxide content and the LDL susceptibility to oxidation were higher; 2) total cholesterol, LDL-cholesterol, apoB and CE-OOH were negatively correlated with the content of a-tocopherol; 3) there was a positive correlation between the content of lipid-soluble antioxidants and the resistance of LDL to oxidation; and 4) CE-OOH and TL-OOH were positively correlated with total cholesterol and LDL-cholesterol.
Effect of L-Carnitine on Skeletal Muscle Lipids and Oxidative Stress in Rats Fed High-Fructose Diet  [PDF]
Panchamoorthy Rajasekar,Carani Venkatraman Anuradha
Experimental Diabetes Research , 2007, DOI: 10.1155/2007/72741
Abstract: There is evidence that high-fructose diet induces insulin resistance, alterations in lipid metabolism, and oxidative stress in rat tissues. The purpose of this study was to evaluate the effect of L-carnitine (CAR) on lipid accumulation and peroxidative damage in skeletal muscle of rats fed high-fructose diet. Fructose-fed animals (60 g/100 g diet) displayed decreased glucose/insulin (G/I) ratio and insulin sensitivity index (ISI0,120) indicating the development of insulin resistance. Rats showed alterations in the levels of triglycerides, free fatty acids, cholesterol, and phospholipids in skeletal muscle. The condition was associated with oxidative stress as evidenced by the accumulation of lipid peroxidation products, protein carbonyls, and aldehydes along with depletion of both enzymic and nonenzymic antioxidants. Simultaneous intraperitoneal administration of CAR (300 mg/kg/day) to fructose-fed rats alleviated the effects of fructose. These rats showed near-normal levels of the parameters studied. The effects of CAR in this model suggest that CAR supplementation may have some benefits in patients suffering from insulin resistance.
Increased Methylglyoxal Formation with Upregulation of Renin Angiotensin System in Fructose Fed Sprague Dawley Rats  [PDF]
Indu Dhar, Arti Dhar, Lingyun Wu, Kaushik M. Desai
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0074212
Abstract: The current epidemic of obesity and type 2 diabetes is attributed to a high carbohydrate diet, containing mainly high fructose corn syrup and sucrose. More than two thirds of diabetic patients have hypertension. Methylglyoxal is a highly reactive dicarbonyl generated during glucose and fructose metabolism, and a major precursor of advanced glycation end products (AGEs). Plasma methylglyoxal levels are increased in hypertensive rats and diabetic patients. Our aim was to examine the levels of methylglyoxal, mediators of the renin angiotensin system and blood pressure in male Sprague-Dawley rats treated with a high fructose diet (60% of total calories) for 4 months. The thoracic aorta and kidney were used for molecular studies, along with cultured vascular smooth muscle cells (VSMCs). HPLC, Western blotting and Q-PCR were used to measure methylglyoxal and reduced glutathione (GSH), proteins and mRNA, respectively. Fructose treated rats developed a significant increase in blood pressure. Methylglyoxal level and protein and mRNA for angiotensin II, AT1 receptor, adrenergic α1D receptor and renin were significantly increased, whereas GSH levels were decreased, in the aorta and/or kidney of fructose fed rats. The protein expression of the receptor for AGEs (RAGE) and NF-κB were also significantly increased in the aorta of fructose fed rats. MG treated VSMCs showed increased protein for angiotensin II, AT1 receptor, and α1D receptor. The effects of methylglyoxal were attenuated by metformin, a methylglyoxal scavenger and AGEs inhibitor. In conclusion, we report a strong association between elevated levels of methylglyoxal, RAGE, NF-κB, mediators of the renin angiotensin system and blood pressure in high fructose diet fed rats.
Effects of EPA and Vitamin E on Serum Enzymatic Antioxidants and Peroxidation Indices in Patients with Type II Diabetes Mellitus
SH Sarbolouki,M Djalali,AR Dorosty,MR Eshraghian
Iranian Journal of Public Health , 2010,
Abstract: Background: Diabetes mellitus is associated with chronic changes in peripheral arteries because of oxidative stress and insufficient antioxidative defense mechanism. Omega-3 fatty acid supplementation could be effective in some diabetes complications; however, polyunsaturated fatty acids may increase lipid peroxidation. This study aimed to determine whether eicosapentaenoic acid alone or in conjunction with vitamin E had differential effects on serum antioxidants and peroxidation indices."nMethods: This double-blind, placebo-controlled trial was carried out on 136 patients with type II diabetic mellitus (age 48.8±4.4 yr, BMI 27.8±1.7 kg/m2). The four groups of the study either received two grams of omega-3 fatty acids, 400 IU of vitamin E, a combination of the two or placebo for three months. Their serum total antioxidant capacity, enzymatic antioxidants and peroxidation indices were assessed."nResult: Fasting serum TAC increased in EPA+E (10.7%, P< 0.001) and E groups (7.5%, P< 0.05). SOD, G-PX and G-RD increased in EPA group (7.3%, 5.1%, and 8.4%, P< 0.05, respectively). MDA and protein carbonyl decreased in EPA and E groups (respectively, 12.5%, 7.6% P< 0.05, P< 0.05; 13%, 15.3% P< 0.001, P< 0.05). After adjustment for baseline values, age, sex, BMI and duration of diagnosed diabetes, protein carbonyl decreased in EPA+E and E group (30.7%, 15.3%; P< 0.05 respectively) relative to the placebo group."nConclusion: EPA, by itself has a statistically significant effect on serum total antioxidant capacity, enzymatic antioxidants and peroxidation indices in diabetic patients compared to EPA+E or E alone. Trial registration: ClinicalTrials.gov NCT00817622
Garlic improves insulin sensitivity and associated metabolic syndromes in fructose fed rats
Raju Padiya, Tarak N Khatua, Pankaj K Bagul, Madhusudana Kuncha, Sanjay K Banerjee
Nutrition & Metabolism , 2011, DOI: 10.1186/1743-7075-8-53
Abstract: Male Sprague Dawley rats weighing 200-250 gm body weight were divided into 3 groups (n = 7 per group) and fed diet containing 65% cornstarch (Control group) and 65% fructose (Diabetic group) for 8 weeks. The third group (Dia+Garl group) was fed both 65% fructose and raw garlic homogenate (250 mg/kg/day) for 8 weeks. Whole garlic cloves were homogenized with water to make a fresh paste each day.At the end of 8 weeks, serum glucose, insulin, triglyceride and uric acid levels, as well as insulin resistance, as measured by glucose tolerance test, were significantly (p < 0.01) increased in fructose fed rats (Diabetic group) when compared to the cornstarch fed (Control) rats. Administration of raw garlic to fructose fed rats (Dia+Garl group) significantly (p < 0.05) reduced serum glucose, insulin, triglyceride and uric acid levels, as well as insulin resistance when compared with fructose fed rats. Garlic also normalised the increased serum levels of nitric oxide (NO) and decreased levels of hydrogen sulphide (H2S) after fructose feeding. Although body weight gain and serum glycated haemoglobin levels of fructose fed rats (Diabetic group) were not significantly different from control rats, significant (p < 0.05) reduction of these parameters was observed in fructose fed rats after garlic administration (Dia+Garl group). Significant (p < 0.05) increase in TBARS and decrease in GSH was observed in diabetic liver. Catalase was not significantly affected in any of the groups. Administration of raw garlic homogenate normalised both hepatic TBARS and GSH levels.Our study demonstrates that raw garlic homogenate is effective in improving insulin sensitivity while attenuating metabolic syndrome and oxidative stress in fructose-fed rats.Type 2 diabetes mellitus is the most common form of diabetes comprising 80% of all diabetic population. The World Health Organization has predicted that developing countries would have to bear the major burden of this disease. It has been estimated
HYPOGLYCEMIC EFFECT OF 2-HYDROXYCHALCONE ON HIGH FRUCTOSE FED DIABETIC RAT
K. Jegatheesan et al.
International Journal of Pharmaceutical Sciences and Research , 2012,
Abstract: The objective of the project work was to study the effect of Hypoglycemic and Hypolipidemic activity of 2- hydroxychalcone on high fructose diet induced insulin resistance in male Wister Albino rats. Rats were rendered insulin resistant by feeding 66% (w/w) fructose and 1.1% (v/w) coconut oil mixed with normal pellet diet (NPD) for 3 weeks. Insulin resistance high fructose diabetic rats receiving hydroxychalcone intraperitoneally (i.p.) at the dose of 25mg/kg body weight daily for 7 consecutive days. At the end of the study blood glucose, serum insulin, glycosylated haemoglobin was estimated. The tissue was used for the assay of enzyme activity of Hexokinase, Glycogen, Glu-6-phosphatase and fru-1, 6 bis phosphatase were also estimated. Fructose diet with 2-hydroxychalcone significantly reduced the blood glucose, insulin, glu-6-phosphatase, fru-1, 6 bis phosphatase and significantly increase the hexokinase and glycogen activity. The flavonoid present in the cinnamon 2-hydroxychalcone were found to exhibit a significant Hypoglycemic activity in fructose fed insulin resistant rats.
Lipid Peroxidation Alterations in Type 2 Diabetic Patients
A. Marjani
Pakistan Journal of Biological Sciences , 2010,
Abstract: It was studied that type 2 diabetes mellitus is connected with increased plasma lipid peroxidation (lipid peroxidation expressed as malondialdehyde). This review aimed to evaluate the state of lipid peroxidation among type 2 diabetic subjects. Present finding showed that lipid peroxidation increased in type 2 diabetes mellitus. Increased lipid peroxidation maybe is associated with some diseases such as cancer, cardiovascular diseases and diabetes mellitus. Lipid peroxidation has an important role in the pathogenesis and the complications of diabetes. Antioxidants have been found to prevent the progression and occurrence of diabetes. There are several mechanisms that may cause lipid peroxidation affront in diabetic subjects, although, their precise contributions are not completely clear. We proposed that production of free radicals can be reduced by preventing high blood glucose levels and by the control of instabilities in blood glucose levels. A contributor to these instabilities in blood glucose is glycaemic control by using of fast blood sugar test. Furthermore, the earlier assessment of the advancement of diabetes that firmly control of blood glucose can be obtained; the greater will be the decrease in diabetic complications. Patients with type 2 diabetes may have very high physiological antioxidants requirements.
Changes in Antioxidants and Lipid Peroxidation in Workers of A Pesticide Production Factory
H.R Joshaghani,A.R Ahmadi
Journal of School of Public Health and Institute of Public Health Research , 2008,
Abstract: Background and Aim: Organophosphate compoounds are cholinesterase activity inhibitors. Contact with them cause changes in the blood antioxidant enzyme levels and lipid peroxidation. The aim of this research was to investigate the simultaneous changes in cholinesterase, total serum antioxidant levels, and activities of some of the erythrocyte antioxidant enzymes and find possible correlations among these variables in pesticide factory workers. Materials and Methods: This research was a cohort study carried out, during 2006, on the employees of a pesticide factory in Golestan Province, Iran. Blood samples were taken at the beginning (n=81 subjects) and after 3 months (n=63, of the initial 81). Erythrocyte glutathione peroxidase (GPx), superoxide dismutase (SOD) and total antioxidant levels were determined enzymatically (Randox, UK) and serum SOD was measured by the ELISA method (IBL, Germany). For the determination of malondialdehyde (MDA) a chemical method (based on thiobarbituric acid) was used. Confidence interval was 95% for all statistical tests.Results: Levels of serum and erythrocyte SOD, serum MDA, and both serum and eryhthrocyte GPx significantly increased (paired t-test, p<0.05), while the serum total antioxidant level decreased (paired t-test, p<0.05). No statistically significnt correlation was seen between cholinesterase and changes in the other variables. Conclusion: Contact with organophosphorus compounds will cause increases in lipid peroxidation and decreases in total antioxidants. It is suggested that, while more severe physical protective measures are taken, nutritional supplements be taken by the personnel to increase protection against hazardous materials.
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