Evaluation of the Effect of an α-Adrenergic Blocker, a PPAR-γ Receptor Agonist, and a Glycemic Regulator on Chronic Kidney Disease in Diabetic Rats

Int J Mol Sci. 2024 Oct 23;25(21):11372. doi: 10.3390/ijms252111372.

Abstract

Diabetic nephropathy (DN) is a globally widespread complication of diabetes mellitus (DM). Research indicates that pioglitazone and linagliptin mitigate the risk of DN by reducing inflammation, oxidative stress, and fibrosis. The role of tamsulosin in DN is less studied, but it may contribute to reducing oxidative stress and inflammatory responses. The protective effects of combining pioglitazone, linagliptin, and tamsulosin on the kidneys have scarcely been investigated. This study examines the individual and combined effects of these drugs on DN in Wistar rats. Diabetic rats were treated with tamsulosin, pioglitazone, and linagliptin for six weeks. We assessed food and water intake, estimated glomerular filtration rate (eGFR), histological markers, urea, creatinine, glucose, NF-κB, IL-1, IL-10, TGF-β, and Col-IV using immunofluorescence and qPCR. The DN group exhibited hyperglycaemia, reduced eGFR, and tissue damage. Tamsulosin and linagliptin improved eGFR, decreased urinary glucose, and repaired tissue damage. Pioglitazone and its combinations restored serum and urinary markers and reduced tissue damage. Linagliptin lowered serum creatinine and tissue injury. In conclusion, tamsulosin, linagliptin, and pioglitazone demonstrated renoprotective effects in DN.

Keywords: chronic kidney disease; diabetic nephropathy; hyperglycaemia; linagliptin; pioglitazone; tamsulosin.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental* / complications
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetic Nephropathies* / drug therapy
  • Diabetic Nephropathies* / metabolism
  • Diabetic Nephropathies* / pathology
  • Glomerular Filtration Rate / drug effects
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Linagliptin* / pharmacology
  • Linagliptin* / therapeutic use
  • Male
  • PPAR gamma* / agonists
  • PPAR gamma* / metabolism
  • Pioglitazone* / pharmacology
  • Pioglitazone* / therapeutic use
  • Rats
  • Rats, Wistar*
  • Renal Insufficiency, Chronic / drug therapy
  • Renal Insufficiency, Chronic / metabolism
  • Renal Insufficiency, Chronic / pathology
  • Tamsulosin / pharmacology
  • Tamsulosin / therapeutic use

Substances

  • PPAR gamma
  • Pioglitazone
  • Linagliptin
  • Tamsulosin
  • Blood Glucose
  • Hypoglycemic Agents