ABSTRACT
Background: Oxidative stress induces renal dysfunction in diabetes, in which renal mitochondrial disturbance was implicated. Vitamin C (VC) supplementation may ameliorate the renal dysfunction in diabetics. However, it is not clear whether VC supplementation is effective for renal mitochondrial disturbances in diabetes. Objective: Investigate whether long-term continuous VC supplementation could ameliorate the renal mitochondrial disturbances in streptozotocin (STZ)-induced diabetic rats. Methods: Thirty-five male Sprague-Dawley rats were used, and diabetes was induced by an injection of STZ. The rats were divided into three groups: control rats (CON), STZ-induced diabetic rats (STZ), and diabetic rats supplemented by vitamin C (STZ-VC). The CON and STZ rats were given tap water, while STZ-VC rats received VC (1 g/L) every day for eight, 24 and 52 weeks. The kidney was isolated and homogenized. Oxygen comsumption (Vo2) was measured in mitochondria homogenate using an oxygen consumption monitor. Based on Vo2 tracings, the respiration control index (RCI) and P/O ratio (= ADP/ O ratio) were measured at week 8, 24 and 52. Results: At week eight, using either glutamate plus malate (for site I) or succinate (for site II) as substrates, both RCI and P/O ratio were not significantly different among three groups. The P/O ratio in STZ and STZ-VC rats increased from eight to 52 weeks after VC supplementation. At week 24, the P/O ratio at site II was normalized in STZ-VC rat. The increased P/O ratio (only site I) and the increased RCI (only site II) of STZ-VC rats were slower than those of STZ rats. Conclusion: Short-term VC supplementation might not influence the renal mitochondrial activity. The long-term VC supplementation could ameliorate the mitochondrial disturbances induced in STZ-induced diabetic rats.
ABSTRACT
Background: Deficiency of vitamin C (L-ascorbic acid; AA) may induce renal glomular dysfunction in diabetes. Few data are available for the role of continuous upplementation of AA on glomerular dysfunction and pathologyinduced during diabetes. Objective: To investigate long-term effects of AA supplementation on glomerular changes in streptozotocin (STZ)-induced diabetic rats. Methods: Diabetes was induced in Sprague-Dawley rats (180-220 g) by injection of STZ (55 mg/kg bw, iv). The rats were divided into controls (CON), AA-supplemented controls (CON-AA), diabetic (STZ) and AA-supplemented diabetic rats (STZ-AA). AA (1 g/L) was continuously supplemented to the rats for 4, 8, 16 and 24 weeks. The glomerular filtration rate (GFR), effective renal plasma flow (ERPF), renal vascular resistance (RVR) malondialdehyde (MDA) and transforming growth factor-β1 (TGF-β1) levels were measured in the renal cortex. Glomerular morphology was examined histologically. Renal hypertrophic index was calculated using kidney-to-body weight ratio (KW/BW). Results: Decreases in GFR and ERPF were ameliorated at week 16 and deteriorated at week 24 after AA supplementation in STZ-AA rats. High blood glucose concentration was attenuated only at week 16. MAD and TGF-β1 levels in renal cortex decreased significantly in STZ-AA rats at week 16 but not at week 24. The number of abnormal glomeruli and KW/BW decreased significantly at week 16 in STZ-AA rats. Conclusion: Long-term supplementation of AA may ameliorate the glomerular changes induced by diabetes.