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Abstract: PO0926

Esculin Restores Kidneys Mitochondrial Function in the Early Stage of Experimental Diabetic Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Serralha, Robson Souza, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Rodrigues, Inri, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Bertolini, Angela, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Lima, Deyse, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Nascimento, Moises, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Mouro, Margaret G., Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Punaro, Giovana, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Visoná, Iria, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Rodrigues, Adelson, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Higa, Elisa Mieko Suemitsu, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil

Group or Team Name

  • Laboratory of Nitric Oxide and Oxidative Stress
Background

Diabetes mellitus (DM) is a chronic disease which progresses with many complications such as diabetic nephropathy (DN). Mitochondria are the main producer of reactive oxygen species (ROS) in a hyperglycemic condition, consuming oxygen without providing ATP to the cell. In turn, ROS act as a trigger to activation of inflammatory processes. Coumarin derivatives, as esculin, reduced oxidative damage seen in intestinal inflammation, arthritis and cognitive impairment related to diabetes. The aim of this study was to evaluate the effects of esculin on mitochondrial function and on the kidneys cortex in the DN development in rats.

Methods

DM was induced in 7-week-old male Wistar rats, using a single dose of streptozocin (60 mg/kg; i.v) and confirmed with blood glucose ≥ 200mg/dL. The animals received daily doses of esculin (50 mg/kg, p.o.) or its vehicle, during 8 weeks. After this period they were euthanized under anesthesia and the kidneys cortex were collected for histology and mitochondria isolation, to be analyzed by high resolution respirometry. Statistical analysis was performed in GraphPad Prism 6. The results are described as mean ± SEM, significance defined for p < 0.05.

Results

Esculin reduced 24 hs proteinuria in DM rats. The histological analysis of kidneys cortex showed the presence of intense inflammatory lymphomononuclear infiltrate, mild fibrosis and interstitial atrophy characterized by collagen IV deposition in diabetic animals, that were not observed in any of those treated with esculin. In addition, esculin restored mitochondrial function in the kidneys cortex of diabetic rats as analyzed by glycolysis (3.08 ± 0.17 vs 2.39 ± 0.08; p < 0.05) and β-oxidation substrates (4.75 ± 0.08 vs 3.68 ± 0.20; p < 0.05).

Conclusion

Esculin restored mitochondrial function in DM rats and probably through ROS control, reduced the kidney lesions. We suggest the use of esculin as an adjuvant therapy to control the development of DN.

Funding

  • Government Support - Non-U.S.