Abstract
Diabetic nephropathy (DN) is the most frequent cause of the end-stage renal disease (ESRD) in about 33% of diabetic patients. The present study aimed to explore the renoprotective effects of simvastatin (SV) and rosuvastatin (RSU) on the kidney of streptozotocin (STZ)-induced diabetic Sprague-Dawley (SD) rat model. As a result of induction of diabetes, serum [cystatin C, transforming growth factor-beta (TGF-β), and 8-hydroxy-2' -deoxyguanosine (8-OHdG)] and tissue [interleukin 1 beta (IL-1β), interleukin 10 (IL-10), prostaglandin E2 (PGE2), cytochrome c, malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), GSH/GSSG ratio) markers showed significant increase than negative controls except tissue total glutathione (tGSH). Both SV and RSU significantly shifted the levels back toward near non-diabetic values. Both exerted the same renoprotective effect indicated by a significant decrease in cystatin C. However, SV significantly lowered IL-10, GSH/GSSG ratio, MDA, and 8-OHdG than RSU. Similarly, RSU significantly lowered cytochrome c and GSSG than SV. In conclusion, SV and RSU have differential renoprotective effects via alteration of growth factor, inflammatory, oxidative stress, DNA damage, and apoptotic signaling pathways.
Highlights
The impact of diabetes on health resides in a series of complications that characterize this disease [1].Hyperglycemia-induced microvascular complications are the main cause of diabetic nephropathy (DN)
All animal procedures were performed according to an approved protocol and following regulations of the local committee on the care and use of experimental animals of Alexandria University according to the guidelines of the National Institutes of Health (NIH)
Induction of diabetes was confirmed by a test for blood glucose level >200 mg/dL, 48 hours after STZ injection [6]
Summary
The impact of diabetes on health resides in a series of complications that characterize this disease [1]. Hyperglycemia-induced microvascular complications are the main cause of diabetic nephropathy (DN). One-third of all diabetic patients will develop DN [2, 3], which constitutes the most frequent cause of the end-stage renal disease (ESRD) [1]. Reactive Oxygen Species (ROS) and subsequent cellular damage trigger induction of glucose homeostasis transcriptional factors, the proinflammatory cytokines (such as IL-1β), and growth factors (such as TGF-β1) [4,5,6]. The mechanism by which oxidative stress can induce apoptosis may involve increased peroxidation of membrane lipids, increased oxidative injury to macromolecules, changes in cellular redox potential, or depletion of glutathione [7, 8].
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