Malaysian Propolis and Metformin Synergistically Mitigate Kidney Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Rats

Molecules. 2021 Jun 5;26(11):3441. doi: 10.3390/molecules26113441.

Abstract

Diabetic nephropathy is reported to occur as a result of the interactions between several pathophysiological disturbances, as well as renal oxidative stress and inflammation. We examined the effect of Malaysian propolis (MP), which has anti-hyperglycemic, antioxidant and anti-inflammatory properties, on diabetes-induced nephropathy. Diabetic rats were either treated with distilled water (diabetic control (DC) group), MP (300 mg/kg b.w./day), metformin (300 mg/kg b.w./day) or MP + metformin for four weeks. We found significant increases in serum creatinine, urea and uric acid levels, decreases in serum sodium and chloride levels, and increase in kidney lactate dehydrogenase activity in DC group. Furthermore, malondialdehyde level increased significantly, while kidney antioxidant enzymes activities, glutathione level and total antioxidant capacity decreased significantly in DC group. Similarly, kidney immunoexpression of nuclear factor kappa B, tumor necrosis factor-α, interleukin (IL)-1β and caspase-3 increased significantly, while IL-10 immunoexpression decreased significantly in DC group relative to normal control group. Histopathological observations for DC group corroborated the biochemical data. Intervention with MP, metformin or both significantly mitigated these effects and improved renal function, with the best outcome following the combined therapy. MP attenuates diabetic nephropathy and exhibits combined beneficial effect with metformin.

Keywords: Malaysian propolis; diabetes; inflammation; metformin; nephropathy; oxidative stress.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / administration & dosage*
  • Antioxidants / pharmacology
  • Creatinine / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / metabolism
  • Drug Synergism
  • L-Lactate Dehydrogenase / metabolism
  • Male
  • Metformin / administration & dosage*
  • Metformin / pharmacology
  • Oxidative Stress / drug effects
  • Propolis / administration & dosage*
  • Propolis / pharmacology
  • Rats
  • Streptozocin
  • Up-Regulation
  • Urea / blood
  • Uric Acid / blood

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Uric Acid
  • Streptozocin
  • Urea
  • Propolis
  • Metformin
  • Creatinine
  • L-Lactate Dehydrogenase