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Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells.

Alarifi S, Ali D, Alkahtani S, Siddiqui MA, Ali BA - Onco Targets Ther (2013)

Bottom Line: Arsenic trioxide elicited a significant (P < 0.01) reduction in glutathione (15.67% and 26.52%), with a concomitant increase in malondialdehyde level (67.80% and 72.25%; P < 0.01), superoxide dismutase (76.42% and 81.09%; P < 0.01), catalase (73.33% and 76.47%; P < 0.01), and reactive oxygen species generation (44.04% and 56.14%; P < 0.01) after 24 and 48 hours of exposure, respectively.Statistically significant (P < 0.01) induction of DNA damage was observed by the comet assay in cells exposed to arsenic trioxide.The results demonstrate that arsenic trioxide induces apoptosis and genotoxicity in human hepatocellular carcinoma cells through reactive oxygen species and oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Cell and Molecular Laboratory, Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia;

ABSTRACT

Background: Arsenic is a ubiquitous environmental toxicant, and abnormalities of the skin, lung, kidney, and liver are the most common outcomes of long-term arsenic exposure. This study was designed to investigate the possible mechanisms of genotoxicity induced by arsenic trioxide in human hepatocellular carcinoma cells.

Methods and results: A mild cytotoxic response of arsenic trioxide was observed in human hepatocellular carcinoma cells, as evident by (3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) and lactate dehydrogenase assays after 24 and 48 hours of exposure. Arsenic trioxide elicited a significant (P < 0.01) reduction in glutathione (15.67% and 26.52%), with a concomitant increase in malondialdehyde level (67.80% and 72.25%; P < 0.01), superoxide dismutase (76.42% and 81.09%; P < 0.01), catalase (73.33% and 76.47%; P < 0.01), and reactive oxygen species generation (44.04% and 56.14%; P < 0.01) after 24 and 48 hours of exposure, respectively. Statistically significant (P < 0.01) induction of DNA damage was observed by the comet assay in cells exposed to arsenic trioxide. It was also observed that apoptosis occurred through activation of caspase-3 and phosphatidylserine externalization in human hepatocellular carcinoma cells exposed to arsenic trioxide.

Conclusion: The results demonstrate that arsenic trioxide induces apoptosis and genotoxicity in human hepatocellular carcinoma cells through reactive oxygen species and oxidative stress.

No MeSH data available.


Related in: MedlinePlus

(A) Lipid peroxide, (B) glutathione, (C) superoxide dismutase (D) and catalase levels in human hepatocellular carcinoma cells after exposure to arsenic trioxide for 24 and 48 hours.Notes: Each value represents the mean ± standard error of three experiments performed in duplicate. *P < 0.01 versus control.Abbreviations: SOD, Superoxide dismutase; MDA, Malondialdehyde, GSH Glutathione; H2O2, hydrogen per oxide.
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f4-ott-6-075: (A) Lipid peroxide, (B) glutathione, (C) superoxide dismutase (D) and catalase levels in human hepatocellular carcinoma cells after exposure to arsenic trioxide for 24 and 48 hours.Notes: Each value represents the mean ± standard error of three experiments performed in duplicate. *P < 0.01 versus control.Abbreviations: SOD, Superoxide dismutase; MDA, Malondialdehyde, GSH Glutathione; H2O2, hydrogen per oxide.

Mentions: The ability of arsenic trioxide to induce oxidative stress was evaluated by measuring levels of reactive oxygen species, lipid peroxidation, glutathione, superoxide dismutase, and catalase in the hepatocellular carcinoma cells. The results showed that arsenic trioxide induced generation of intracellular reactive oxygen species in a dose-dependent and time-dependent manner (Figure 3A–C). Arsenic trioxide-induced oxidative stress was further evidenced by depletion of glutathione and induction of lipid peroxidation, superoxide dismutase, and catalase with increasing concentrations and duration of arsenic trioxide exposure (Figure 4A–D).


Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells.

Alarifi S, Ali D, Alkahtani S, Siddiqui MA, Ali BA - Onco Targets Ther (2013)

(A) Lipid peroxide, (B) glutathione, (C) superoxide dismutase (D) and catalase levels in human hepatocellular carcinoma cells after exposure to arsenic trioxide for 24 and 48 hours.Notes: Each value represents the mean ± standard error of three experiments performed in duplicate. *P < 0.01 versus control.Abbreviations: SOD, Superoxide dismutase; MDA, Malondialdehyde, GSH Glutathione; H2O2, hydrogen per oxide.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3569381&req=5

f4-ott-6-075: (A) Lipid peroxide, (B) glutathione, (C) superoxide dismutase (D) and catalase levels in human hepatocellular carcinoma cells after exposure to arsenic trioxide for 24 and 48 hours.Notes: Each value represents the mean ± standard error of three experiments performed in duplicate. *P < 0.01 versus control.Abbreviations: SOD, Superoxide dismutase; MDA, Malondialdehyde, GSH Glutathione; H2O2, hydrogen per oxide.
Mentions: The ability of arsenic trioxide to induce oxidative stress was evaluated by measuring levels of reactive oxygen species, lipid peroxidation, glutathione, superoxide dismutase, and catalase in the hepatocellular carcinoma cells. The results showed that arsenic trioxide induced generation of intracellular reactive oxygen species in a dose-dependent and time-dependent manner (Figure 3A–C). Arsenic trioxide-induced oxidative stress was further evidenced by depletion of glutathione and induction of lipid peroxidation, superoxide dismutase, and catalase with increasing concentrations and duration of arsenic trioxide exposure (Figure 4A–D).

Bottom Line: Arsenic trioxide elicited a significant (P < 0.01) reduction in glutathione (15.67% and 26.52%), with a concomitant increase in malondialdehyde level (67.80% and 72.25%; P < 0.01), superoxide dismutase (76.42% and 81.09%; P < 0.01), catalase (73.33% and 76.47%; P < 0.01), and reactive oxygen species generation (44.04% and 56.14%; P < 0.01) after 24 and 48 hours of exposure, respectively.Statistically significant (P < 0.01) induction of DNA damage was observed by the comet assay in cells exposed to arsenic trioxide.The results demonstrate that arsenic trioxide induces apoptosis and genotoxicity in human hepatocellular carcinoma cells through reactive oxygen species and oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Cell and Molecular Laboratory, Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia;

ABSTRACT

Background: Arsenic is a ubiquitous environmental toxicant, and abnormalities of the skin, lung, kidney, and liver are the most common outcomes of long-term arsenic exposure. This study was designed to investigate the possible mechanisms of genotoxicity induced by arsenic trioxide in human hepatocellular carcinoma cells.

Methods and results: A mild cytotoxic response of arsenic trioxide was observed in human hepatocellular carcinoma cells, as evident by (3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) and lactate dehydrogenase assays after 24 and 48 hours of exposure. Arsenic trioxide elicited a significant (P < 0.01) reduction in glutathione (15.67% and 26.52%), with a concomitant increase in malondialdehyde level (67.80% and 72.25%; P < 0.01), superoxide dismutase (76.42% and 81.09%; P < 0.01), catalase (73.33% and 76.47%; P < 0.01), and reactive oxygen species generation (44.04% and 56.14%; P < 0.01) after 24 and 48 hours of exposure, respectively. Statistically significant (P < 0.01) induction of DNA damage was observed by the comet assay in cells exposed to arsenic trioxide. It was also observed that apoptosis occurred through activation of caspase-3 and phosphatidylserine externalization in human hepatocellular carcinoma cells exposed to arsenic trioxide.

Conclusion: The results demonstrate that arsenic trioxide induces apoptosis and genotoxicity in human hepatocellular carcinoma cells through reactive oxygen species and oxidative stress.

No MeSH data available.


Related in: MedlinePlus