title: New mechanistic approach of inorganic palladium toxicity: impairment in mitochondrial electron transfer.
abstract: Human activities have increased the levels of palladium (Pd) that are progressively accumulating in the environment. The growing evidence of Pd toxicity has become the focus of serious concern for the environment, organisms and humans, with little data on the mechanism of Pd toxicity. Recent studies have suggested that mitochondria have a key role in Pd toxicity via mitochondrial membrane potential collapse and depletion of the cellular glutathione (GSH) level. Therefore, it was decided to determine the mechanistic toxicity of Pd towards isolated mitochondria via new and reliable methods. Isolated liver and kidney mitochondria were obtained by differential ultracentrifugation and incubated with different concentrations of Pd (100-400 μM). Our results showed that Pd induced mitochondrial dysfunction via an increase in mitochondrial ROS production and membrane potential collapse, which correlated to cytochrome c release. Also, increased disturbance in oxidative phosphorylation was also shown by the increase in ADP/ATP ratio in Pd-treated mitochondria, which indicates mitochondrial dysfunction in isolated liver and kidney mitochondria. Our results suggest that Pd-induced toxicity is the result of a disruptive effect on the mitochondrial respiratory chain, increasing the chance of cell death signaling. In addition, it is supposed that kidney tissue is more susceptible to Pd exposure than liver tissue.
authors.affiliation: Zanjan Applied Pharmacology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran and Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, P. O. Box: 45139-56184, Zanjan, Iran. jamal_hossini@yahoo.com.
authors.forename: M-J
authors.initials: MJ
authors.lastname: Hosseini
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, P. O. Box: 45139-56184, Zanjan, Iran. jamal_hossini@yahoo.com.
authors.forename: I
authors.initials: I
authors.lastname: Jafarian
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, P. O. Box: 45139-56184, Zanjan, Iran. jamal_hossini@yahoo.com.
authors.forename: S
authors.initials: S
authors.lastname: Farahani
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, P. O. Box: 45139-56184, Zanjan, Iran. jamal_hossini@yahoo.com.
authors.forename: R
authors.initials: R
authors.lastname: Khodadadi
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, P. O. Box: 45139-56184, Zanjan, Iran. jamal_hossini@yahoo.com.
authors.forename: S H
authors.initials: SH
authors.lastname: Tagavi
authors.affiliation: Zanjan Applied Pharmacology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: P
authors.initials: P
authors.lastname: Naserzadeh
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Mohammadi-Bardbori
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, P. O. Box: 45139-56184, Zanjan, Iran. jamal_hossini@yahoo.com.
authors.forename: N
authors.initials: N
authors.lastname: Arghavanifard
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D045304:Cytochromes c / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D010165:Palladium / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010165:Palladium; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D045304:Cytochromes c