Cardiac Oxidative Stress And Matrix Metalloproteinases Activities In Streptozotocin-Induced Metabolic Syndrome And Diabetes Mellitus In Wistar Male Rats

Diabetes mellitus (DM) is one of the most common diseases in the world. Among its effects are an increase in the risk of cognitive impairment, including Alzheimer’s disease, and blood-brain barrier (BBB) dysfunction. DM is characterized by high blood glucose levels that are caused by either lack of insulin (Type I) or resistance to the actions of insulin (Type II). The phenotypes of these two types are dramatically different, with Type I animals being thin, with low levels of leptin as well as insulin, whereas Type II animals are often obese with high levels of both leptin and insulin. The best characterized change in BBB dysfunction is that of disruption. The brain regions that are disrupted, however, vary between Type I vs Type II DM, suggesting that factors other than hyperglycemia, perhaps hormonal factors such as leptin and insulin, play a regionally diverse role in BBB vulnerability or protection. Some BBB transporters are also altered in DM, including P-glycoprotein, lowdensity lipoprotein receptor-related protein 1, and the insulin transporter as other functions of the BBB, such as brain endothelial cell (BEC) expression of matrix metalloproteinases (MMPs) and immune cell trafficking. Pericyte loss secondary to the increased oxidative stress of processing excess glucose through the Krebs cycle is one mechanism that has shown to result in BBB disruption. Vascular endothelial growth factor (VEGF) induced by advanced glycation endproducts can increase the production of matrix metalloproteinases, which in turn affects tight junction proteins, providing another mechanism for BBB disruption as well as effects on P-glycoprotein. Through the enhanced expression of the redox-related mitochondrial transporter ABCB10, redox-sensitive transcription factor NF-E2 related factor-2 (Nrf2) inhibits BEC-monocyte adhesion. Several potential therapies, in addition to those of restoring euglycemia, can prevent some aspects of BBB dysfunction. Carbonic anhydrase inhibition decreases glucose metabolism and so reduces oxidative stress, preserving pericytes and blocking or reversing BBB disruption. Statins or N-acetylcysteine can reverse the BBB opening in some models of DM, fibroblast growth factor-21 improves BBB permeability through an Nrf2-dependent pathway, and nifedipine or VEGF improves memory in DM models. In summary, DM alters various aspects of BBB function through a number of mechanisms. A variety of treatments based on those mechanisms, as well as restoration of euglycemia, may be able to restore BBB functions., including reversal of BBB disruption.

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Oxidative stress and inflammation, two features associated with a high percentage body fat, and that may lead to diabetes mellitus and metabolic syndrome

BioFactors ◽

10.1002/biof.1459 ◽

2018 ◽

Vol 45 (1) ◽

pp. 35-42 ◽

Cited By ~ 13

Author(s):

Susan Darroudi ◽

Narges Fereydouni ◽

Maryam Tayefi ◽

Mahsa Ahmadnezhad ◽

Parvin Zamani ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Metabolic Syndrome ◽

Body Fat ◽

Percentage Body Fat

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Renoprotective and blood pressure-lowering effect of dietary soy protein via protein kinase C βII inhibition in a rat model of metabolic syndrome

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y09-110 ◽

2010 ◽

Vol 88 (1) ◽

pp. 28-37 ◽

Cited By ~ 11

Author(s):

Nallasamy Palanisamy ◽

Periyasamy Viswanathan ◽

Mambakkam Katchapeswaran Ravichandran ◽

Carani Venkataraman Anuradha

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Metabolic Syndrome ◽

Renal Function ◽

Protein Kinase C ◽

Insulin Sensitivity ◽

Protein Kinase ◽

Soy Protein ◽

Male Rats ◽

Kinase C

We studied whether substitution of soy protein for casein can improve insulin sensitivity, lower blood pressure (BP), and inhibit protein kinase C βII (PKCβII) activation in kidney in an acquired model of metabolic syndrome. Adult male rats were fed 4 different diets: (i) starch (60%) and casein (20%) (CCD), (ii) fructose (60%) and casein (20%) (FCD), (iii) fructose (60%) and soy protein (20%) (FSD), and (iv) starch (60%) and soy protein (20%) (CSD). Renal function parameters, BP, pressor mechanisms, PKCβII expression, oxidative stress, and renal histology were evaluated after 60 days. FCD rats displayed insulin resistance and significant changes in body weight, kidney weight, urine volume, plasma and urine electrolytes accompanied by significant changes in renal function parameters compared with CCD rats. Elevated BP, plasma angiotensin-converting enzyme (ACE) activity, renal oxidative stress, and reduced nitrite (NO) and kallikrein activity were observed. Western blot analysis revealed enhanced renal expression of membrane-associated PKCβII in the FCD group. Histology showed fatty infiltration and thickening of glomeruli while urinary protein profile revealed a 5-fold increase in albumin. Substitution of soy protein for casein improved insulin sensitivity, lowered BP and PKCβII activation and restored renal function. Antioxidant action, inhibitory effect on ACE and PKCβII activation, and increased availability of kinins and NO could be contributing mechanisms for the benefits of dietary soy protein.

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The effects of gasotransmitters inhibition on biochemical and haematological parameters and oxidative stress in propofol-anaesthetized Wistar male rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0029 ◽

2019 ◽

Vol 97 (11) ◽

pp. 1073-1079 ◽

Cited By ~ 1

Author(s):

M. Djuric ◽

T. Nikolic Turnic ◽

S. Kostic ◽

S. Stankovic ◽

K. Radonjic ◽

...

Keyword(s):

Oxidative Stress ◽

Bolus Injection ◽

Troponin T ◽

Protoporphyrin Ix ◽

Male Rats ◽

High Density Lipoproteins ◽

Zinc Protoporphyrin ◽

Synthase Inhibitor ◽

And Oxidative Stress ◽

Wistar Male Rats

This study aimed to investigate the effects of propofol through evaluating its interaction with nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO). Wistar male rats were divided in 4 groups: (1) bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (2) Nω-nitro-l-arginine methyl ester (L-NAME; NO synthase inhibitor, 60 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (3) DL-propargylglycine (DL-PAG; H2S synthase inhibitor, 50 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (4) zinc protoporphyrin IX (ZnPPIX; CO synthase inhibitor, 50 μmol/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.). Increased levels of albumins, low-density lipoproteins, alkaline phosphatase, amylase, high-sensitivity Troponin T, and fibrinogen were found in L-NAME + propofol group. Platelet crit, platelet count, total cholesterol, and high-density lipoproteins were elevated in ZnPPIX + propofol group. Hydrogen peroxide was increased in all groups treated with gasotransmitters inhibitors. Reduced glutathione was reduced in all groups, superoxide dismutase activity only in L-NAME + propofol. The effect of propofol on various biochemical, haematological, and oxidative stress markers may be at least in part mediated through interaction with 3 estimated gasotransmitters.

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Cardiovascular function in male and female JCR:LA-cp rats: effect of high-fat/high-sucrose diet

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00535.2016 ◽

2017 ◽

Vol 312 (4) ◽

pp. H742-H751 ◽

Cited By ~ 10

Author(s):

Ian Hunter ◽

Amanda Soler ◽

Gregory Joseph ◽

Brenda Hutcheson ◽

Chastity Bradford ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Syndrome ◽

Cardiovascular Function ◽

Western Diet ◽

Female Rats ◽

Male Rats ◽

High Fat ◽

Male And Female ◽

Normal Chow ◽

High Sucrose

Thirty percent of the world population is diagnosed with metabolic syndrome. High-fat/high-sucrose (HF/HS) diet (Western diet) correlates with metabolic syndrome prevalence. We characterized effects of the HF/HS diet on vascular (arterial stiffness, vasoreactivity, and coronary collateral development) and cardiac (echocardiography) function, oxidative stress, and inflammation in a rat model of metabolic syndrome (JCR rats). Furthermore, we determined whether male versus female animals were affected differentially by the Western diet. Cardiovascular function in JCR male rats was impaired versus normal Sprague-Dawley (SD) rats. HF/HS diet compromised cardiovascular (dys)function in JCR but not SD male rats. In contrast, cardiovascular function was minimally impaired in JCR female rats on normal chow. However, cardiovascular function in JCR female rats on the HF/HS diet deteriorated to levels comparable to JCR male rats on the HF/HS diet. Similarly, oxidative stress was markedly increased in male but not female JCR rats on normal chow but was equally exacerbated by the HF/HS diet in male and female JCR rats. These results indicate that the Western diet enhances oxidative stress and cardiovascular dysfunction in metabolic syndrome and eliminates the protective effect of female sex on cardiovascular function, implying that both males and females with metabolic syndrome are at equal risk for cardiovascular disease. NEW & NOTEWORTHY Western diet abolished protective effect of sex against cardiovascular disease (CVD) development in premenopausal animals with metabolic syndrome. Western diet accelerates progression of CVD in male and female animals with preexisting metabolic syndrome but not normal animals. Exacerbation of baseline oxidative stress correlates with accelerated progression of CVD in metabolic syndrome animals on Western diet.

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The Connection of Periodontal Disease and Diabetes Mellitus: The Role of Matrix Metalloproteinases and Oxidative Stress

Serbian Journal of Experimental and Clinical Research ◽

10.2478/sjecr-2019-0051 ◽

2019 ◽

Vol 0 (0) ◽

Cited By ~ 2

Author(s):

Dragana Stanisic ◽

Radmila Obradovic ◽

Sanja Vujovic ◽

Milica Jovanovic ◽

Vladimir Zivkovic

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Matrix Metalloproteinases ◽

Periodontal Disease ◽

Membrane Receptors ◽

World Health ◽

Dental Biofilm ◽

Periodontal Tissues ◽

And Oxidative Stress

Abstract Diabetes mellitus, a chronic disease considered by the World Health Organization to be an epidemic, is now recognized as one of the factors behind the onset of periodontal disease. The connection between periodontal disease, which is an irreversible inflammatory disease of the supporting tissue of the teeth, and systemic diseases is reflected in the existence of common risk factors, subgingival dental biofilm, as a constant source of proinflamma-tory cytokines synthesized intensely in inflammatory periodontium. Diabetes mellitus leads to increased oxidative stress in periodontal tissues causing worsening of the disease and periodontopathy exacerbates deficiency of pancreatic β-cells. The most important role in primary inflammatory response in the pathogenesis of periodontopathy is played by neutrophils. Neutrophils cause periodontium destruction by the release of enzymes (matrix metalloproteinases), cytotoxic substances (free radicals, reactive oxygen and nitrogen species) and the expression of membrane receptors. Matrix metalloproteinases within the “protease network” are critical to many physiological and pathological processes, including immunity, inflammation, bone resorption and wound healing. Matrix metalloproteinases levels are elevated in patients with metabolic syndrome and diabetes mellitus, which may contribute to more frequent complications. In this paper, the review of available literature data shows the correlation between periodontal disease and diabetes mellitus, as well as the role of matrix metalloproteinases and oxidative stress in these. In this regard, determining the value of matrix metalloproteinases may be helpful in the diagnosis of periodontal disease complicated by diabetes mellitus. Also, the parameters of oxidative stress could help to clarify the mechanisms of pathogenesis and etiology of periodontal disease, or indicate the potential benefit of antioxidant supplementation in these individuals. As the role of matrix metalloproteinases has not been fully clarified in the pathogenesis of periodontopathy, additional studies will be needed to indicate their importance.

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Oxidative stress and tissue hypoxia as factors contributing to the development of prostate and bladder dysfunction in metabolic syndrome

Experimental and Сlinical Urology ◽

10.29188/2222-8543-2021-14-2-14-22 ◽

2021 ◽

Vol 14 (2) ◽

pp. 14-22

Author(s):

V.I. Kirpatovsky ◽

◽

S.A. Golovanov ◽

V.V. Drozhzheva ◽

L.V. Kudryavtseva ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Metabolic Syndrome ◽

Confocal Microscopy ◽

Functional State ◽

Oxidant Stress ◽

Reactive Oxygen ◽

Tissue Hypoxia ◽

Male Rats ◽

Oxygen Species

Introduction. The development of oxidative stress and nonspecific inflammation is one of the leading factors in the development of benign prostatic hyperplasia (BPH) and associated urination disorders in metabolic syndrome (MS). However, the specific mechanisms of these processes are not entirely clear. The purpose of the study. To study the activity of reactive oxygen species production and the functional state of mitochondria in the prostate and bladder and their role in the dysfunction of these organs using an experimental model of MS induction in rats. Material and methods. In 10 adult mongrel male rats MS was induced by keeping them on a high-calorie diet with an increased content of carbohydrates and fats for 3 months. 10 rats kept on a standard vivarium diet served as controls. The development of MS was confirmed by characteristic changes in the biochemical analysis of blood (hyperglycemia, hyperuricemia, dyslipidemia, hyperinsulinemia). In both series of rats, sections of the native prostate and bladder were examined by laser confocal microscopy and stained with fluorescent probes that characterize the activity of the production of reactive oxygen species (dichlorofluorescein-DCF) and the functional state of the mitochondria (tetramethylrodamine ether – TMRE). The activity of a number of intracellular enzymes (AST, ALT. Alkaline phosphatase, LDH) was investigated in the tissues and urine. Results. In rats with MS, the development of BPH and hypertrophy of the bladder were revealed, confirmed histologically. The study of sections of both organs by confocal microscopy revealed a significant increase in the production of reactive oxygen species by their cells and a decrease in the functional activity of mitochondria, which indicated the development of oxidant stress and tissue hypoxia. In the prostate, this was accompanied by a decrease in the secretory activity of the prostate glands, and in the bladder – the release of cytoplasmic enzymes from damaged cells into the urine, indicating cell damage. Conclusion. The causes of the development of a non-specific inflammatory process in the prostate and bladder, leading to dysfunction of these organs in MS, are increased production of reactive oxygen species and the development of tissue hypoxia.

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