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Comparative evaluation of torasemide and furosemide on rats with streptozotocin-induced diabetic nephropathy
Somasundaram Arumugam1, Remya Sreedhar1, Shizuka Miyashita1
1Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City 956-8603, Japan.
Abstract:
Nephropathy is one of the complications of diabetes mellitus in human and experimental animals. There are various pathological renal remodeling processes leading to diabetic nephropathy because of the chronic hyperglycemia during diabetes mellitus. Various reports suggest the involvement of oxidative stress, inflammation and fibrosis during this progression. As antihypertensive drugs are reported to provide renoprotection in various animal models and clinical studies, we have carried out this study to identify the effect of torasemide, a loop diuretic, against streptozotocin-induced diabetic nephropathy and compare with furosemide. Here we have performed the measurement of blood and urine parameters and renal protein expression levels for measuring the disease severity in streptozotocin-induced diabetic rats treated torasemide or furosemide and compared with the vehicle treated rats. Furosemide treatment significantly increased the urinary protein excretion when compared with the normal rats. Torasemide treatment has reduced the expression of mineralocorticoid receptor and oxidative stress marker p67phox levels with improved mRNA levels of heme oxygenase-1 in the kidneys. In addition, torasemide treated diabetic rats showed significantly reduced expression of renal fibrosis related proteins when compared with the vehicle treated diabetic rats. Although furosemide treatment has produced improvement, its effects are comparably less than that of torasemide. Thus with the present results, we can suggest that torasemide treatment can improve the diabetic kidney disease in this rat model and which is superior to furosemide against renal fibrotic remodeling.
Insights
Torasemide treatment improved diabetic kidney disease in rats by reducing fibrosis and oxidative stress. This loop diuretic showed superior renoprotective effects compared to furosemide in this diabetic nephropathy model.
Area of Science:
- Nephrology
- Pharmacology
- Diabetology
Background:
- Diabetic nephropathy is a major complication of diabetes mellitus.
- Chronic hyperglycemia drives pathological renal remodeling, involving oxidative stress, inflammation, and fibrosis.
- Antihypertensive drugs may offer renoprotection in diabetic kidney disease.
Purpose of the Study:
- To investigate the renoprotective effect of torasemide against streptozotocin-induced diabetic nephropathy in rats.
- To compare the efficacy of torasemide with furosemide in mitigating diabetic kidney disease progression.
Main Methods:
- Induction of diabetic nephropathy in rats using streptozotocin.
- Treatment with torasemide, furosemide, or vehicle.
- Measurement of blood and urine parameters.
- Assessment of renal protein and mRNA expression levels related to disease severity, oxidative stress, and fibrosis.
Main Results:
- Torasemide reduced mineralocorticoid receptor and p67phox expression, and increased heme oxygenase-1 mRNA levels.
- Torasemide significantly decreased renal fibrosis-related proteins compared to vehicle.
- Furosemide increased urinary protein excretion and showed less improvement than torasemide.
Conclusions:
- Torasemide demonstrates significant renoprotective effects in a rat model of diabetic nephropathy.
- Torasemide is superior to furosemide in ameliorating renal fibrotic remodeling associated with diabetic kidney disease.
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