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. Lederer3†,
- Michael Brownlee4,
- Miriam F. Weiss2 and
- Vincent M. Monnier15
- 1Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio
- 2Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio
- 3Institut für Lebensmittelchemie, Universität Hohenheim, Stuttgart, Germany
- 4Albert Einstein College of Medicine, Bronx, New York
- 5Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, Ohio
- Address correspondence and reprint requests to Vincent M. Monnier, Case Western Reserve University, Department of Pathology, School of Medicine, 2085 Adelbert Rd., Cleveland, OH 44106. E-mail: vmm3{at}po.cwru.edu
Abstract
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.
- AGE, advanced glycation end product
- CML, carboxymethyl-lysine
- DNP, dinitrophenol
- ERC, electron respiratory chain
- HPLC, high-performance liquid chromatography
- TCC, tricarboxylic acid cycle
Footnotes
- †
† Deceased.
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- Accepted September 21, 2004.
- Received May 11, 2004.
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