Sulforaphane prevents maleic acid-induced nephropathy by modulating renal hemodynamics, mitochondrial bioenergetics and oxidative stress

Food Chem Toxicol. 2018 May:115:185-197. doi: 10.1016/j.fct.2018.03.016. Epub 2018 Mar 13.

Abstract

Maleic acid (MA)-induced nephropathy that is characterized by proteinuria, glycosuria, phosphaturia and a deficient urinary acidification and concentration. Sulforaphane (SF) is an indirect antioxidant that shows nephroprotective effects. The aim of the present work was to test the pre-treatment with SF against the MA-induced nephropathy. Wistar rats (230-260 g) were separated in the following groups: control, MA (which received 400 mg/kg of MA), SF + MA (which received MA and 1 mg/kg of SF each day for four days) and SF (which only received SF). MA induced proteinuria, an increase in urinary excretion of N-acetyl-β-d-glucosaminidase, and a decrease in plasma glutathione peroxidase activity, renal blood flow, and oxygenation and perfusion of renal cortex. All these impairments correlated with higher levels of oxidative damage markers and exacerbated superoxide anion production on renal cortex. Moreover, MA impaired mitochondrial bioenergetics associated to complex I, mitochondrial membrane potential and respiratory control index and increased the mitochondrial production of hydrogen peroxide. Further it disrupted mitochondrial morphology. SF prevented all the above-described alterations. In conclusion, the protective effect of SF against MA-induced nephropathy is associated with preservation of mitochondrial bioenergetics, amelioration of oxidative stress and improvement of renal hemodynamics and renal cortex oxygenation.

Keywords: Acute kidney injury; Kidney; Maleate; Maleic acid; Renal; Sulforaphane.

MeSH terms

  • Animals
  • Energy Metabolism / drug effects
  • Hemodynamics
  • Humans
  • Isothiocyanates / administration & dosage*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney Diseases / chemically induced
  • Kidney Diseases / metabolism
  • Kidney Diseases / prevention & control*
  • Male
  • Maleates / adverse effects*
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects*
  • Plant Extracts / administration & dosage*
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Sulfoxides

Substances

  • Isothiocyanates
  • Maleates
  • Plant Extracts
  • Reactive Oxygen Species
  • Sulfoxides
  • maleic acid
  • sulforaphane