On the oxidative damage by cadmium to kidney mitochondrial functions

Abstract

In the kidney, the accumulation of heavy metals such as Cd2+ produces mitochondrial dysfunctions, i.e., uncoupling of the oxidative phosphorylation, inhibition of the electron transport through the respiratory chain, and collapse of the transmembrane electrical gradient. This derangement may be due to the fact that Cd2+ induces the transition of membrane permeability from selective to nonselective via the opening of a transmembrane pore. In fact, Cd2+ produces this injury through the stimulation of oxygen-derived radical generation, inducing oxidative stress. Several molecules have been used to avoid or even reverse Cd2+-induced mitochondrial injury, for instance, cyclosporin A, resveratrol, dithiocarbamates, and even EDTA. The aim of this study was to explore the possibility that the antioxidant tamoxifen could protect mitochondria from the deleterious effects of Cd2+. Our results indicate that the addition of 1 μmol/L Cd2+ to mitochondria collapsed the transmembrane electrical gradient, induced the release of cytochrome c, and increased both the generation of H2O2 and the oxidative damage to mitochondrial DNA (among other measured parameters). Of interest, these mitochondrial dysfunctions were ameliorated after the addition of tamoxifen.

Microcystin-LR Combined with Cadmium Exposures and the Risk of Chronic Kidney Disease: A Case–Control Study in Central China

“…A previous animal study also found that subchronic low-dose Cd exposure may cause renal injury, including decreased renal function, destruction of the renal structure, and inflammation, in a dose-dependent manner . The mechanism of Cd-induced kidney injury is relatively clear, including oxidative stress, DNA damage, inflammation, mitochondrial dysfunction, apoptosis, and autophagy. , In addition, it has been proposed that Cd exposure can eliminate reserves of kidney function, which may increase an individual’s susceptibility to other risk factors of kidney failure …”

“…37 The mechanism of Cd-induced kidney injury is relatively clear, including oxidative stress, DNA damage, inflammation, mitochondrial dysfunction, apoptosis, and autophagy. 38,39 In addition, it has been proposed that Cd exposure can eliminate reserves of kidney function, which may increase an individual's susceptibility to other risk factors of kidney failure. 33 MC-LR and Cd coexist widely in the aquatic ecosystem with the aggravation of environmental pollution and the continuous discharge of industrial, agricultural, and domestic sewage.…”

Cadmium-Induced Kidney Injury: Oxidative Damage as a Unifying Mechanism

“…Cadmium can enter mitochondria and accumulate therein [ 113 , 114 ]. This is likely facilitated by mitochondrial membrane channels, and solute molecule carriers and receptors [ 114 ].…”

Choline dehydrogenase interacts with SQSTM1 to activate mitophagy and promote coelomocyte survival in <i>Apostichopus japonicus</i> following <i>Vibrio splendidus</i> infection

“…While mitochondria are the primary sites of ROS generation, excessive ROS accumulation can impair mitochondrial membrane potential, leading to irreversible oxidative damage and cell death ( Huang et al, 2019 ; Murphy et al, 2016 ; Orrenius et al, 2007 ; Wang et al, 2020 ). However, a reduction in membrane potential can also lead to the recruitment of mitochondrial receptors, which can combine with autophagy adapters and LC3 to activate mitophagy ( Pavón et al, 2019 ). Although most studies on the regulatory mechanisms of mitophagy have focused on the PINK1-PRKN pathway, emerging evidence suggests that this pathway is not the sole mechanism, and mitophagy can still occur in the absence of parkin ( Villa et al, 2018 ).…”