The heavy metals lead and cadmium are cytotoxic to human bone osteoblasts via induction of redox stress


Autoři: Ayat Al-Ghafari aff001;  Ekramy Elmorsy aff002;  Emad Fikry aff002;  Majed Alrowaili aff005;  Wayne G. Carter aff004
Působiště autorů: Biochemistry Department, Faculty of Science, King AbdulAziz University, Jeddah, Saudi Arabia aff001;  Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, Mansoura City, Egypt aff002;  Department of Pathology, Faculty of Medicine, Northern Border University, Arar; Saudi Arabia aff003;  School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby, United Kingdom aff004;  Department of Surgery, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia aff005
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225341

Souhrn

The heavy metals (HMs) lead and cadmium are persistent environmental pollutants capable of inducing ill-health in exposed individuals. One of the primary sites of accumulation and potential damage from HMs is bone, and we therefore examined the acute effects of lead and cadmium on human bone osteoblasts in vitro over a concentration range of 0.1 μM to 1mM, and for 3, 6, 12, 24, and 48 hour exposures. Incubation of osteoblasts with either lead or cadmium reduced cell viability in a concentrations and exposure durations dependent manner, as measured using MTT and LDH assays. Cytotoxicity was significant from 0.1 μM concentrations after 48 hour exposures. Both HMs damaged cellular bioenergetics with reductions of ATP production, mitochondrial complex activities, and aerobic respiration. There was a concomitant elevation of reactive oxygen species, with induction of redox stress measured as increased lipid peroxidation, and depleted cellular redox defense systems via reduced superoxide dismutase and catalase activity and cellular glutathione levels. Both HMs induced nuclear activation of Nrf2, presumably to increase transcription of antioxidant responsive genes to combat oxidative stress. Incubation of osteoblasts with HMs also compromised the secretion of procollagen type 1, osteocalcin, and alkaline phosphatase. Pre-incubation of osteoblasts with reduced glutathione prior to challenge with HMs lessened the cytotoxicity of the HMs, indicative that antioxidants may be a beneficial treatment adjunct in cases of acute lead or cadmium poisoning.

Klíčová slova:

Cadmium – Glutathione – Metallic lead – Mitochondria – MTT assay – Oxidation-reduction reactions – Reactive oxygen species – Osteoblasts


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