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

Al-Ghafari, Ayat; Elmorsy, Ekramy; Fikry, Emad; Alrowaili, Majed; Carter, Wayne Grant


Ayat Al-Ghafari

Ekramy Elmorsy

Emad Fikry

Majed Alrowaili


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 2 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.


Al-Ghafari, A., Elmorsy, E., Fikry, E., Alrowaili, M., & Carter, W. G. (2019). The heavy metals lead and cadmium are cytotoxic to human bone osteoblasts via induction of redox stress. PLoS ONE, 14(11),

Journal Article Type Article
Acceptance Date Nov 15, 2019
Online Publication Date Nov 22, 2019
Publication Date Nov 22, 2019
Deposit Date Nov 21, 2019
Publicly Available Date Nov 22, 2019
Journal PLoS ONE
Electronic ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 14
Issue 11
Article Number e0225341
Keywords Antioxidants; Bone; Cadmium; Lead; Osteoblasts; Redox stress
Public URL
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