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Abstract
Objective: To investigate the effect of 2-chloroadenosine (2CADO) and 1,3-dipropyl-8-sulfophenylxanthine (DPSPX) on renal oxidative stress of diabetic Wistar and SHR rats. Design and Methods: On day 0, male Wistar (240–300 g) and SHR (12 weeks) rats were i.p. injected with streptozotocin (65 mg/Kg; STZ) or vehicle (SHAM). On day 14, osmotic mini-pumps were i.p. implanted for 2CADO (5 mg/Kg/d; CADO) or DPSPX (90 μg/Kg/h; DPSPX) administration for 7 days. Catheters were implanted for systolic blood pressure (SBP) measurement. Plasma, kidney and 24h-urine samples were collected at the end of the study. Glucose and hydrogen peroxide (H2O2) were quantified with commercial kits. Catalase (Cat) activity was measured by a spectrophotometric assay and thiobarbituric acid reactive substances (TBARS) by a colorimetric assay. Statistical comparisons were made by Student t-test and ANOVA followed by Dunnett's Multiple Comparison test as appropriate. Results: Results are summarized in the Table below. Diabetes increased plasma glucose in both strains. Treatment with 2CADO or DPSPX decreased plasma glucose in STZ-Wistar rats. Diabetes increased both Cat activity and H2O2 production in the medula of Wistar rats and treatment with 2CADO attenuated this increase. In SHR rats, medulary production of H2O2 was decreased after induction of diabetes and even further after 2-CADO administration. Urinary excretion of H2O2 did not change in both strains, with either treatment. Urinary TBARS increased with the induction of diabetes and this increase was attenuated in both strains by 2CADO. SBP decreased in SHR rats after diabetes induction and treatment with 2-CADO caused a further decrease. Conclusions: STZ-induced diabetes is associated with increased renal oxidative stress in Wistar and SHR rats. Treatment with 2CADO reduced oxidative stresse in Wistar but not SHR rats, although this protective effect seems to be mediated by different mechanisms. Further studies will help to clarify the differences observed between the two strains.
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