Abstract
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.
Highlights
Heavy metals (HMs) such as lead, cadmium, mercury, and arsenic are worldwide environmental pollutants with multiple adverse health effects [1]
There is a need to establish the threshold lead or cadmium exposure that triggers osteoblast damage, and delineate the mechanisms of toxicity. To address this we have considered the cytotoxic effects of lead and cadmium after direct application to human osteoblasts in vitro
Human osteoblasts were incubated with the HMs, lead (Pb) or cadmium (Cd) over a broad concentration range of 0.1 μM to 1 mM, and the level of cytotoxicity quantified after 3, 6, 12, 24, and 48 hours using MTT and LDH assays
Summary
Heavy metals (HMs) such as lead, cadmium, mercury, and arsenic are worldwide environmental pollutants with multiple adverse health effects [1]. Humans may experience occupational or environmental exposure to HMs usually via inhalation, dermal, or ingestion routes, primarily via contaminated air, soil, water, or foodstuffs, respectively [2]. For some HMs, bone can be a primary target for HM accumulations and toxic damage. Bones may sequester and store lead, which can be subsequently remobilized during childhood or pregnancy, with. Osteoblasts and lead and cadmium neurotoxic or teratogenic properties, respectively [3,4,5]. Higher bone mineral density (BMD) has been attributed to higher lead exposure in children [6], reduced BMD correlated with lead exposure in certain adult cohorts [7]
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