Renal damage induced by cadmium and its possible therapy by mitochondrial transplantation

Chem Biol Interact. 2022 Jul 1:361:109961. doi: 10.1016/j.cbi.2022.109961. Epub 2022 Apr 30.

Abstract

Cadmium (Cd) is one of the most toxic metals without biological function, and its accumulation in living organisms has been reported. The kidney is a target organ in Cd toxicity; it has been observed that Cd causes kidney damage even at low concentrations, and Cd damage can quickly progress to chronic kidney disease. The mitochondria play a fundamental role in the nephrotoxicity of Cd; Cd enters the mitochondria and affects the electron transport system (ETS), increases the production of reactive oxygen species (ROS), decreases the mitochondrial membrane potential (Δψm), alters mitochondrial dynamics, induces mutations in mitochondrial deoxyribonucleic acid (mtDNA) and decreased biogenesis leading to increased mitophagy, autophagy, and inevitably apoptosis. Existing therapies to treat Cd nephrotoxicity are currently based on antioxidant and chelating compounds, but despite their promising effects, they have some limitations; therefore, Cd nephrotoxicity continues to represent a global health problem. Mitochondrial transplantation is a new experimental approach with positive results by reversing mitochondrial alterations in cardiac and kidney dysfunction mainly caused by oxidative stress. Hence, the current review discusses the role of mitochondria in Cd-induced toxicity in the kidney and proposes mitochondrial transference as a novel therapy based on transplanting healthy mitochondria to cells with Cd-compromised mitochondria. This review is the first to propose mitochondrial transplantation as a treatment for heavy metal-induced kidney damage.

Keywords: Cadmium; Kidney injury; Mitochondrial dysfunction; Mitochondrial transplantation; Oxidative stress.

Publication types

  • Review

MeSH terms

  • Apoptosis
  • Cadmium* / toxicity
  • Humans
  • Kidney
  • Kidney Diseases* / chemically induced
  • Mitochondria / metabolism
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species
  • Cadmium