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Sodium Glucose Cotransporter-2 Inhibitor Empagliflozin Increases Antioxidative Capacity and Improves Renal Function
Habib Yaribeygi1, Mohammad Amin Hemmati2, Fatemeh Nasimi1
1Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran.
Introduction:
There are several pathologic mechanisms involved in diabetic nephropathy, but the role of oxidative stress seems to be one of the most important. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs that might also have some other effects in addition to lowering glucose. The aim of this study was to evaluate the possible effects of the SGLT2 inhibitor empagliflozin on oxidative stress and renal function in diabetes.
Methods:
Male Wistar rats were randomly divided into four groups: control, control-treated, diabetic, and diabetic-treated (n = 8 per group). Diabetes was induced by a single intraperitoneal dose of streptozotocin (50 mg/kg). The treated animals received empagliflozin for 5 weeks (20 mg/kg/day/po). All groups were sacrificed on the 36th day, and blood and tissue samples were collected. Serum levels of urea, uric acid, creatinine, and glucose levels were determined. The level of malondialdehyde (MDA) and glutathione (GLT), as well as the activity of catalase (CAT) and superoxide dismutase (SOD), was measured in all groups. Data were analyzed using one-way Anova and paired T-tests, and p ≤ 0.05 was considered significant.
Results:
Diabetes significantly increased urea (p < 0.001), uric acid (p < 0.001), and creatinine (p < 0.001) in the serum, while the activities of CAT (p < 0.001) and SOD (p < 0.001) were reduced. GLT was also reduced (p < 0.001), and MDA was increased (p < 0.001) in non-treated animals. Treatment with empagliflozin improved renal function, as shown by a reduction in the serum levels of urea (p = 0.03), uric acid (p = 0.03), and creatinine (p < 0.001). Empagliflozin also increased the antioxidant capacity by increasing CAT (p = 0.035) and SOD (p = 0.02) activities and GLT content (p = 0.01) and reduced oxidative damage by lowering MDA (p < 0.001).
Conclusions:
It seems that uncontrolled diabetes induces renal insufficiency by decreasing antioxidant defense mechanisms and inducing oxidative stress. Empagliflozin might have additional benefits in addition to lowering glucose--reversing these processes, improving antioxidative capacity, and improving renal function.
Insights
Empagliflozin treatment improved renal function and reduced oxidative stress in diabetic rats. This suggests SGLT2 inhibitors may offer additional benefits beyond glucose control for diabetic nephropathy.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Diabetic nephropathy involves oxidative stress as a key pathologic mechanism.
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of antidiabetic drugs with potential additional effects.
- Empagliflozin is an SGLT2 inhibitor investigated for its impact on oxidative stress and kidney function in diabetes.
Purpose of the Study:
- To evaluate the effects of empagliflozin on oxidative stress markers and renal function in a rat model of diabetes.
- To determine if empagliflozin can mitigate diabetes-induced renal damage.
Main Methods:
- Male Wistar rats were divided into control, control-treated, diabetic, and diabetic-treated groups (n=8).
- Diabetes was induced with streptozotocin; treated groups received empagliflozin (20 mg/kg/day) for 5 weeks.
- Serum urea, uric acid, creatinine, and tissue oxidative stress markers (MDA, GLT, CAT, SOD) were measured.
Main Results:
- Diabetes significantly increased serum urea, uric acid, and creatinine, while decreasing antioxidant enzymes (CAT, SOD) and glutathione (GLT), and increasing malondialdehyde (MDA).
- Empagliflozin treatment significantly reduced serum urea, uric acid, and creatinine.
- Empagliflozin treatment increased antioxidant capacity (CAT, SOD, GLT) and reduced oxidative damage (MDA).
Conclusions:
- Uncontrolled diabetes leads to renal insufficiency via reduced antioxidant defenses and increased oxidative stress.
- Empagliflozin demonstrates potential benefits beyond glucose lowering, including reversing oxidative stress and improving renal function in diabetic nephropathy.
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