Paradoxical Effects of Green Tea (Camellia Sinensis) and Antioxidant Vitamins in Diabetic Rats

Mustata, Georgian T.; Roșca, Mariana G.; Biemel, Klaus M.; Reihl, Oliver; Smith, Mark A.; Viswanathan, Ashwini; Strauch, Christopher; Du, Yunpeng; Tang, Jie; Kern, Timothy S.; Lederer, Markus O.; Brownlee, Michael; Weiss, Miriam F.; Monnier, Vincent M.

doi:10.2337/diabetes.54.2.517

Cited by 126 publications

(88 citation statements)

References 39 publications

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“…67,[85][86][87][88][93][94][95][97][98][99]156 Finally, in experimental diabetes, the use of green tea was associated with an improvement in diabetic nephropathy and retinopathy and associated with a reduction in oxidative stress. 91, 157 The usefulness of these dietary approaches in diabetic patients with hypertension and nephropathy or retinopathy that are on standard treatment deserves to be tested in larger clinical trials. Finally, a better understanding and identification of the basic mechanism of action of different antioxidants in diabetes can lead to better optimization of renal and retinal protection.…”

Section: Discussionmentioning

confidence: 99%

The contribution of hypertension to diabetic nephropathy and retinopathy: the role of inflammation and oxidative stress

2011

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Diabetes and hypertension frequently coexist and constitute the most notorious combination for the pathogenesis of diabetic nephropathy and retinopathy. Large clinical trials have clearly demonstrated that tight control of glycemia and/or blood pressure significantly reduces the incidence and progression of diabetic retinopathy (DR) and nephropathy. However, the mechanism by which hypertension interacts with diabetes to induce and/or exacerbate nephropathy and retinopathy is very unclear. Substantial evidence implicates the involvement of chronic inflammation and oxidative stress in the pathogenesis of DR and nephropathy. In addition, hypertension causes oxidative stress and inflammation in the kidney and retina. In the present review, we summarized data obtained from our research along with those from other groups to better understand the role of hypertension in the pathogenesis of diabetic nephropathy and retinopathy. It is suggested that oxidative stress and inflammation may be common denominators of kidney and retinal damage in the concomitant presence of diabetes and hypertension.

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Section: Discussionmentioning

confidence: 99%

The contribution of hypertension to diabetic nephropathy and retinopathy: the role of inflammation and oxidative stress

2011

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“…3, A-C). In a recent study measuring various antioxidant effects in diabetic and control rats (37), levels of these ODIC cross-links were found to be a mirror image of glucosepane formation in tendon collagen, thereby strongly suggesting that glucosepane and the ODIC cross-links compete for the same modification sites on the collagen molecule, explaining why the much more predominant glucosepane masks the minor cross-links.…”

Section: Table I Spearman Correlation Coefficients (R) Of Measured Skmentioning

confidence: 99%

Glucosepane Is a Major Protein Cross-link of the Senescent Human Extracellular Matrix

Sell

Biemel

Reihl

et al. 2005

Journal of Biological Chemistry

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185

143

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The extracellular matrix in most tissues is characterized by progressive age-related stiffening and loss of proteolytic digestibility that are accelerated in diabetes and can be duplicated by the nonenzymatic reaction of reducing sugars and extracellular matrix proteins. However, most cross-links of the Maillard reaction described so far are present in quantities too low to account for these changes. Here we have determined in human skin and glomerular basement membrane (GBM) collagen the levels of the recently discovered lysinearginine cross-links derived from glucose, methylglyoxal, glyoxal, and 3-deoxyglucosone, i.e. glucosepane, MODIC, GODIC, and DOGDIC, respectively. Insoluble preparations of skin collagen (n ‫؍‬ 110) and glomerular basement membrane (GBM, n ‫؍‬ 28) were enzymatically digested, and levels were measured by isotope dilution technique using liquid chromatography/mass spectrometry. In skin, all cross-links increased with age (p < 0.0001) except DOGDIC (p ‫؍‬ 0.34). In nondiabetic controls, levels at 90 years were 2000, 30, and 15 pmol/mg for glucosepane, MODIC, and GODIC, respectively. Diabetes, but not renal failure, increased glucosepane to 5000 pmol/mg (p < 0.0001), and for all others, increased it to <60 pmol/mg (p < 0.01). In GBMs, glucosepane reached up to 500 pmol/mg of collagen and was increased in diabetes (p < 0.0001) but not old age. In conclusion, glucosepane is the single major cross-link of the senescent extracellular matrix discovered so far, accounting for up to >120 mole% of triple helical collagen modification in diabetes. Its presence in high quantities may contribute to a number of structural and cell matrix dysfunctions observed in aging and diabetes.Reducing sugars react nonenzymatically with proteins to form adducts and cross-links referred to as advanced glycation end products (1). Their accumulation is particularly high in long-lived proteins, such as lens crystallins and collagen, and results in intra-and intermolecular cross-linking. The latter has been hypothesized to result in an age-and diabetes-related stiffening of collagenous tissues and is believed to play an important role in the etiology of atherosclerosis and cardiovascular disease (3) as well as the loss of elasticity in lungs, joints, and skin (4 -6). These age-related processes are markedly accelerated by diabetes and are associated with morbidity and mortality in diabetic individuals (7,8). In skin, protein crosslinking is associated with an age-related loss of elasticity, increased stiffening, and wrinkling (9). However, this process occurs ubiquitously with age, suggesting a fundamental underlying mechanism.Although most of the age-related changes in the extracellular matrix could be duplicated by incubating reducing sugars with proteins, Eble et al. (10) suggested that the major cross-links are not stable to conventional conditions of acid hydrolysis. Indeed, Biemel et al. (11) recently showed that glucose and sugar-derived dicarbonyl intermediates react with human serum albumin to form various acid...

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“…Trolox is a water soluble analog of vitamin E with potent antioxidant properties. Trolox is shown to partially prevent the loss of pericytes in diabetic rats via reducing membrane lipid peroxidation [131]. Another antioxidant, calcium dobesilate, decreased retinal permeability, stabilized BRB, and reduced overexpression of VEGF in diabetic rats [132].…”

Section: Inhibition Of Ros Antioxidants and Hexosamine Pathway As Ementioning

confidence: 99%

Molecular mechanisms of Diabetic Retinopathy, general preventive strategies and novel therapeutic targets

Safi¹,

Qvist²,

Kumar³

et al. 2013

Exp Clin Endocrinol Diabetes

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The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors.

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Paradoxical Effects of Green Tea (Camellia Sinensis) and Antioxidant Vitamins in Diabetic Rats

Cited by 126 publications

References 39 publications

The contribution of hypertension to diabetic nephropathy and retinopathy: the role of inflammation and oxidative stress

The contribution of hypertension to diabetic nephropathy and retinopathy: the role of inflammation and oxidative stress

Glucosepane Is a Major Protein Cross-link of the Senescent Human Extracellular Matrix

Molecular mechanisms of Diabetic Retinopathy, general preventive strategies and novel therapeutic targets

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