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Abstract: PO0711

Oxidative Stress on the Kidney and Heart of Rats with Diabetic Nephropathy Treated with Esculin

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Rodrigues, Inri Faria, Universidade Federal de Sao Paulo Escola Paulista de Medicina, Sao Paulo, SP, Brazil
  • Punaro, Giovana, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Lima, Deyse Yorgos, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • De Bessa, Tiphany Coralie, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Mouro, Margaret G., Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Bertolini, Angela, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Serralha, Robson Souza, 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 is a chronic disease which progresses with complications such as diabetic nephropathy (DN) and diabetic cardiomyopathy. Esculin (ESC) and its metabolite, esculetin, are coumarin derivatives, belonging to the Oleaceae family, found also in some more known species in the southern hemisphere, such as the pink lemon (Citrus limonia). ESC has been related to antioxidant (AO), anti-inflammatory and anti-apoptotic actions. The aim of the present study was to verify the role of oxidative stress (OS) on the kidney and the heart of rats with DN, and the ESC effect on them.

Methods

We used adult male Wistar rats (N=20), Ethics Committee # 3511260318. Normal rats (CTL) or with blood glucose> 200mg/dL, diabetic (DM, treated with streptozotocin 60 mg/kg, IV, single dose), received ESC (50 mg/ kg, via gavage, for 8 weeks). After this period, we collected blood, 24-hr urine, the kidney and heart of these animals. The organs were homogenized for TBARS (OS marker) and Western blotting of OS and apoptosis markers.

Results

Renal function assessed by urea and creatinine was reduced in DM x CTL. Proteinuria and TBARS increased in plasma and urine in DM rats, with a reduction in DM+ESC group (p< 0.05). In DM heart, there were no alterations in TBARS; glutathione, a pro-oxidant, was elevated. In the heart, Nrf-2, responsible for the transcription of several AO, was elevated in the DM, both in its cytoplasmic form and in its active, phosphorylated form. Catalase, an enzymatic AO, and caspase-3 were elevated in DM (p< 0.05).

Conclusion

ESC protected the diabetic kidneys reducing proteinuria and OS. Unlike the kidney, the hearts of DM did not present OS, although glutathione and apoptosis were increased. It is important to note, however, that the increase in AO proteins such as Nrf2 and catalase, suggests that at this early stage of DN, they are still able to protect the cardiac tissue against OS. We believe that the monitoring of this disease evolution can better clarify the role of Redox balance/ imbalance in the heart of diabetic rats. This would be very useful in the approach of prevention and treatment of cardiomyopathy, including the possible use of esculin, with its important antioxidant, anti-inflammatory and anti-apoptotic effects, as an adjuvant therapy.

Funding

  • Government Support – Non-U.S.