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. 2024 Dec 19;13(6):tfae218.
doi: 10.1093/toxres/tfae218. eCollection 2024 Dec.

Fucoxanthin alleviates the cytotoxic effects of cadmium and lead on a human osteoblast cell line

Ekramy M Elmorsy  1   2 , Ayat B Al-Ghafari  3   4 , Huda A Al Doghaither  3
Affiliations

Fucoxanthin alleviates the cytotoxic effects of cadmium and lead on a human osteoblast cell line

Ekramy M Elmorsy et al. Toxicol Res (Camb). .

Abstract

Objective: Cadmium (Cd) and lead (Pb) are non-biodegradable heavy metals (HMs) that persistently contaminate ecosystems and accumulate in bones, where they exert harmful effects. This study aimed to investigate the protective effect of fucoxanthin (FX) against the chemical toxicity induced by Cd and Pb in human bone osteoblasts in vitro, using various biochemical and molecular assays.

Methods: The effect of metals and FX on osteoblasts viability was assayed by MTT, then the effect of Pb, Cd, and FX on the cells' mitochondrial parameters was studied via assays for ATP, mitochondrial membrane potential (MMP), mitochondrial complexes, and lactate production. Also, the effect of metals on oxidative stress was assessed by reactive oxygen species, lipid peroxidation and antioxidant enzymes assays. Also the effect of FX and metals on apoptosis caspases and related genes was assessed.

Results: When Cd and Pb were added to human osteoblast cultures at concentrations ranging from 1-20 μM for 72 h, they significantly reduced osteoblast viability in a time and concentration-dependent manner. The cytotoxic effect of Cd on osteoblasts was greater than that of Pb, with estimated EC50 of 8 and 12 μM, respectively, after 72 h of exposure. FX (10 and 20 μM) alleviated the cytotoxicity of the metals. Bioenergetics assays, including ATP, MMP, and mitochondrial complexes I and III activities, revealed that HMs at 1 and 10 μM concentrations inhibited cellular bioenergetics after 72 h of exposure. Cd and Pb also increased lipid peroxidation and reactive oxygen species while reducing catalase and superoxide dismutase antioxidant activities and oxidative stress-related genes. This was accompanied by increased caspases -3, -8, and - 9 and Bax/bCl-2 ratio. Co-treatment with FX (10 and 20 μM) mitigated the disruption of bioenergetics, oxidative damage, and apoptosis induced by the metals, showing a concentration-dependent pattern to varying extents.

Conclusion: These findings strongly support the role of FX in managing toxicities induced by environmental pollutants in bones and in addressing bone diseases associated with molecular bases of oxidative stress, apoptosis, and bioenergetic disruption.

Keywords: antioxidants; bone; cadmium; fucoxanthin; lead; osteoblasts; redox stress.

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