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

Improved Retinopathy and Renal Mitochondrial Defects but Deterioration of Collagen Matrix Glycoxidation and Cross-Linking

Georgian T. Mustata¹, Mariana Rosca², Klaus M. Biemel³, Oliver Reihl³, Mark A. Smith¹, Ashwini Viswanathan¹, Christopher Strauch¹, Yunpeng Du², Jie Tang², Timothy S. Kern², Markus O. Lederer^3,, Michael Brownlee⁴, Miriam F. Weiss², and Vincent M. Monnier^1,5

¹ Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio
² Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio
³ Institut für Lebensmittelchemie, Universität Hohenheim, Stuttgart, Germany
⁴ Albert Einstein College of Medicine, Bronx, New York
⁵ Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, Ohio

We tested the hypothesis that green tea prevents diabetes-related tissue dysfunctions attributable to oxidation. Diabetic rats were treated daily with tap water, vitamins C and E, or fresh Japanese green tea extract. After 12 months, body weights were decreased, whereas glycated lysine in aorta, tendon, and plasma were increased by diabetes (P < 0.001) but unaffected by treatment. Erythrocyte glutathione and plasma hydroperoxides were improved by the vitamins (P < 0.05) and green tea (P < 0.001). Retinal superoxide production, acellular capillaries, and pericyte ghosts were increased by diabetes (P < 0.001) and improved by green tea and the vitamins (P variable). Lens crystallin fluorescence at 370/440 nm was ameliorated by green tea (P < 0.05) but not the vitamins. Marginal effects on nephropathy parameters were noted. However, suppressed renal mitochondrial NADH-linked ADP-dependent and dinitrophenol-dependent respiration and complex III activity were improved by green tea (P variable). Green tea also suppressed the methylglyoxal hydroimidazolone immunostaining of a 28-kDa mitochondrial protein. Surprising, glycoxidation in tendon, aorta, and plasma was either worsened or not significantly improved by the vitamins and green tea. Glucosepane cross-links were increased by diabetes (P < 0.001), and green tea worsened total cross-linking. In conclusion, green tea and antioxidant vitamins improved several diabetes-related cellular dysfunctions but worsened matrix glycoxidation in selected tissues, suggesting that antioxidant treatment tilts the balance from oxidative to carbonyl stress in the extracellular compartment.

Abbreviations: AGE, advanced glycation end product; CML, carboxymethyl-lysine; DNP, dinitrophenol; ERC, electron respiratory chain; HPLC, high-performance liquid chromatography; TCC, tricarboxylic acid cycle

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