Curcumin prevents cisplatin-induced renal alterations in mitochondrial bioenergetics and dynamic

Food Chem Toxicol. 2017 Sep;107(Pt A):373-385. doi: 10.1016/j.fct.2017.07.018. Epub 2017 Jul 8.

Abstract

Cisplatin is widely used as chemotherapeutic agent for treatment of diverse types of cancer, however, acute kidney injury (AKI) is an important side effect of this treatment. Diverse mechanisms have been involved in cisplatin-induced AKI, such as oxidative stress, apoptosis and mitochondrial damage. On the other hand, curcumin is a polyphenol extracted from the rhizome of Curcuma longa L. Previous studies have shown that curcumin protects against the cisplatin-induced AKI; however, it is unknown whether curcumin can reduce alterations in mitochondrial bioenergetics and dynamic in this model. It was found that curcumin prevents cisplatin-induced: (a) AKI and (b) alterations in the following mitochondrial parameters: bioenergetics, ultrastructure, hydrogen peroxide production and dynamic. In fact, curcumin prevented the increase of mitochondrial fission 1 protein (FIS1), the decrease of optic atrophy 1 protein (OPA1) and the decrease of NAD+-dependent deacetylase sirtuin-3 (SIRT3), a mitochondrial dynamic regulator as well as the increase in the mitophagy associated proteins parkin and phosphatase and tensin homologue (PTEN)-induced putative kinase protein 1 (PINK1). In conclusion, the protective effect of curcumin in cisplatin-induced AKI was associated with the prevention of the alterations in mitochondrial bioenergetics, ultrastructure, redox balance, dynamic, and SIRT3 levels.

Keywords: Bioenergetics; Cisplatin; Curcumin; Kidney; Mitochondria.

MeSH terms

  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / physiopathology
  • Animals
  • Antineoplastic Agents / adverse effects*
  • Apoptosis / drug effects
  • Cisplatin / adverse effects*
  • Curcuma / chemistry
  • Curcumin / administration & dosage*
  • Energy Metabolism / drug effects
  • Humans
  • Hydrogen Peroxide / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Male
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Mitophagy / drug effects
  • Oxidative Stress / drug effects
  • Plant Extracts / administration & dosage*
  • Proteins / genetics
  • Proteins / metabolism
  • Rats
  • Rats, Wistar
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Antineoplastic Agents
  • FIS1 protein, mouse
  • Mitochondrial Proteins
  • Opa3 protein, mouse
  • Plant Extracts
  • Proteins
  • Hydrogen Peroxide
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Curcumin
  • Cisplatin