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

  1. Georgian T. Mustata1,
  2. Mariana Rosca2,
  3. Klaus M. Biemel3,
  4. Oliver Reihl3,
  5. Mark A. Smith1,
  6. Ashwini Viswanathan1,
  7. Christopher Strauch1,
  8. Yunpeng Du2,
  9. Jie Tang2,
  10. Timothy S. Kern2,
  11. Markus O. Lederer3,
  12. Michael Brownlee4,
  13. Miriam F. Weiss2 and
  14. Vincent M. Monnier15
  1. 1Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio
  2. 2Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio
  3. 3Institut für Lebensmittelchemie, Universität Hohenheim, Stuttgart, Germany
  4. 4Albert Einstein College of Medicine, Bronx, New York
  5. 5Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, Ohio
  1. 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}


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.


  • Deceased.

    • Accepted September 21, 2004.
    • Received May 11, 2004.
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