Preventive effect of exercise training on diabetic kidney disease in ovariectomized rats with type 1 diabetes

Abstract

This study evaluated the effects of moderate regular physical exercise on lipid peroxidation, inflammation and renal function and structure in streptozotocin (STZ)-induced ovariectomized diabetic rats. Twenty-four Wistar rats were anesthetized and submitted to bilateral ovariectomy. The rats were divided into four experimental groups: ovariectomized control (OC), ovariectomized trained control (OTC), ovariectomized diabetic (OD), ovariectomized trained diabetic (OTD). The OTD and OTC groups were submitted to treadmill running for four weeks before to diabetes mellitus (DM) induction with STZ (40 mg/kg, i.v) or vehicle injection, respectively, and continued the training for another eight weeks after the injections. Urine samples were collected 24 h after the last training session, and blood samples and kidneys were collected after euthanasia. Our results showed that physical exercise attenuated the loss of body weight and postprandial glucose and improved physical capacity in the OTD group. Lower serum creatinine levels, glycosuria, and proteinuria were also observed in this group. There was no difference in 17β-estradiol levels between the experimental groups. The glomerular and tubulointerstitial changes were attenuated in the OTD group. Expressions of macrophages, lymphocytes, fibronectin, TGF-β1, and NF-κB were reduced in the glomeruli of OTD group. Exercise also reduced macrophages, lymphocytes, and TGF-β1 expression in the tubulointerstitial compartment of the renal cortex of this group. In addition, increased levels of TBARS in the renal cortex of diabetic rats were prevented by exercise in the OTD group. In conclusion, our study shows that physical exercise exerted a renoprotective effect against the progression of diabetic kidney disease in ovariectomized rats. Impact statement To date, no studies have been found evaluating the effects of physical exercise on renal function and structure changes in ovariectomized rats with type 1 diabetes. Therefore, this work emerges with an important tool for strengthening and expanding innovative research on exercise with potential for the prevention of renal diseases in ovariectomized diabetic rats, and future development of studies that seek to increase scientific knowledge about the beneficial effects of physical exercise on renal diseases in humans.

Influence of exercise training on diabetic kidney disease: A brief physiological approach

“…81 Studies have shown that low to moderate intensity aerobic exercise seems to exert renoprotective effects in patients with T1DM and T2DM 18,82–84 and in experimental models of DM. 7,8,85,86 Moderate aerobic exercise improved the insulin sensitivity, glucose uptake 83,87–89 lipid levels, endothelial function, pancreatic beta cell function, and decreased insulin resistance 70,90 , tubular injury, and microalbuminuria in patients with T2DM. 18 Additionally, a recent study has shown that a calorie-restricted diet associated with this type of exercise reduced inflammation and oxidative stress delayed the development of renal failure by postponing renal fibrosis in patients with T2DM in stage 3 DKD.…”

“…30 Evidence suggests that increased expression of ECM proteins in the diabetic kidney is mainly mediated by profibrogenic cytokine TGF-β1. The progressive accumulation of ECM is a critical factor in the progression of DKD, present in both humans 31,32 and experimental animals, 7,8 and contributes to the development of glomerulosclerosis and tubulointerstitial fibrosis. 33,34 Under normal conditions, the main mesangial ECM proteins are fibronectin, laminin, type IV collagen (α1 and α2 chains), and proteoglycans.…”

“…53–56 Studies have shown that renal injury was associated with increased expression of NF-кB in STZ-induced diabetic rats. 8,19,57 Activation of NF-кB in renal cells results in increased chemokine CCL2, also known as MCP-1, which is related to macrophage migration to the site of inflammation into kidney tissue. 50,51 This chemokine has also its production increased from renal tubulointerstitial lesions and hyperglycemic environments in response to oxidative stress and the presence of AII.…”

“…Experimental studies have shown that early stages of DKD are characterized by glomerular hyperfiltration, adaptive renal hypertrophy, and microalbuminuria, which may be attributed to DM-induced hemodynamic and metabolic disorders. 6–8 The perpetuation of these conditions leads to dense proteinuria, loss of nephron, and progressive fall in glomerular filtration rate (GFR). 9,10 Hyperfiltration is an initial common stage observed in patients with type 1 diabetes mellitus (T1DM), which predisposes to the development of micro or macroalbuminuria.…”

“…7 Also, our most recent studies suggest that a reduction of oxidative stress and inflammation induced by exercise can contribute to this process. 8,19…”