title: Adaptive changes in renal mitochondrial redox status in diabetic nephropathy.
abstract: Nephropathy is a serious and common complication of diabetes. In the streptozotocin (STZ)-treated rat model of diabetes, nephropathy does not typically develop until 30 to 45days post-injection, although hyperglycemia occurs within 24h. We tested the hypothesis that chronic hyperglycemia results in a modest degree of oxidative stress that is accompanied by compensatory changes in certain antioxidants and mitochondrial redox status. We propose that as kidneys progress to a state of diabetic nephropathy, further adaptations occur in mitochondrial redox status. Basic parameters of renal function in vivo and several parameters of mitochondrial function and glutathione (GSH) and redox status in isolated renal cortical mitochondria from STZ-treated and age-matched control rats were examined at 30days and 90days post-injection. While there was no effect of diabetes on blood urea nitrogen, measurement of other, more sensitive parameters, such as urinary albumin and protein, and histopathology showed significant and progressive worsening in diabetic rats. Thus, renal function is compromised even prior to the onset of frank nephropathy. Changes in mitochondrial respiration and enzyme activities indicated existence of a hypermetabolic state. Higher mitochondrial GSH content and rates of GSH transport into mitochondria in kidneys from diabetic rats were only partially due to changes in expression of mitochondrial GSH carriers and were mostly due to higher substrate supply. Although there are few clear indicators of oxidative stress, there are several redox changes that occur early and change further as nephropathy progresses, highlighting the complexity of the disease.
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Putt
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhong
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Lash
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D005978:Glutathione / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications; D007672:Kidney Cortex / Q000473:pathology*; D007677:Kidney Function Tests; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013997:Time Factors
chemical_list: D013311:Streptozocin; D005978:Glutathione