Luteolin Attenuates Glycerol-Induced Acute Renal Failure and Cardiac Complications Through Modulation of Kim-1/NF-κB/Nrf2 Signaling Pathways

J Diet Suppl. 2021;18(5):543-565. doi: 10.1080/19390211.2020.1811442. Epub 2020 Sep 16.

Abstract

Acute renal failure (ARF) has been documented as a life-threatening disease with high morbidity and mortality. We investigated the protective effect of Luteolin against ARF. In this study, forty-male Wistar albino rats were randomly divided into four groups (n = 10). Group A received normal saline. Group B received glycerol (10 ml/kg BW, 50% v/v in sterile saline, i.m.). Groups C and D were pretreated with Luteolin 100 and 200 mg/kg for 7 days, and thereafter administered Glycerol (10 ml/kg BW, 50% v/v in sterile saline, i.m.). Administration of glycerol significantly increased systolic blood pressure, diastolic blood pressure and mean arterial pressure. Renal protein carbonyl and xanthine oxidase increased significantly while significant reduction in the activity of renal glutathione peroxidase, glutathione S-transferase and glutathione reductase was observed in the glycerol intoxicated rats. Furthermore, administration of glycerol led to significant increases in serum creatinine and blood urea nitrogen together with reduction in nitric oxide (NO) bioavailability. Immunohistochemistry revealed that glycerol intoxication enhanced expressions of kidney injury molecule 1, nuclear factor kappa beta and cardiac troponin (CTnI). However, Luteolin pretreatment normalized blood pressure, reduced markers of oxidative stress, renal damage, and improved NO bioavailability. Luteolin also downregulated the expressions of kidney injury molecule 1, nuclear factor kappa beta and cardiac troponin. Together, Luteolin might open a novel therapeutic window for the treatment of acute renal failure and cardiac complication.

Keywords: Acute renal failure; Luteolin; glycerol; phytochemicals.

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / drug therapy
  • Acute Kidney Injury* / metabolism
  • Animals
  • Cell Adhesion Molecules
  • Glycerol / metabolism
  • Kidney / metabolism
  • Luteolin / metabolism
  • Luteolin / pharmacology
  • Male
  • NF-E2-Related Factor 2* / metabolism
  • NF-kappa B
  • Oxidative Stress
  • Rats
  • Rats, Wistar
  • Signal Transduction*

Substances

  • Cell Adhesion Molecules
  • Havcr1protein, rat
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Luteolin
  • Glycerol