As2O3 toxicity in rat hepatocytes: manifestation of caspase-mediated apoptosis

Toxicology and Industrial Health
A RayShelley Bhattacharya

Abstract

In India, arsenic contamination in ground water is of immediate environmental concern affecting a large number of inhabitants in Kolkata. Arsenic is known to be one of the most toxic metalloids naturally occurring in the environment giving rise to severe toxic manifestations including cancer. Because arsenic is also used in chemotherapy of leukemia, it was considered worthwhile to concentrate on the mechanism of toxic action in normal hepatocytes which has not been addressed earlier. Rat hepatocytes were isolated and incubated in As(2)O(3) at concentrations of 10, 20, and 40 microM in a time-dependent manner (0, 15, 30 min and 1, 2, and 4 h). The expression of the common stress proteins HSP 70 and 90 throughout the experimental duration confirmed the magnitude of toxic effect imposed by arsenic. Microscopic observations showed clear apoptotic changes in hepatocytes, which were further characterized by DNA ladder formation in time- and concentration-dependent manners. Apoptosis was triggered by caspase activation and over expression of bax at 10 microM As(2)O(3) and at 20 and 40 microM concentrations of As(2)O(3), MAP kinases were found to mediate the apoptotic pathway. Co-treatment of cells with arsenic and caspase inhibitor (A...Continue Reading

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Citations

May 26, 2009·Archives of Environmental Contamination and Toxicology·Byung-Sun ChoiJung-Duck Park
Mar 19, 2014·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Atish RayShelley Bhattacharya
May 29, 2016·Molecular and Biochemical Parasitology·Guoqiang XingHailong Lv
Oct 4, 2012·Toxicology and Industrial Health·Sarmishtha ChatterjeeShelley Bhattacharya
Oct 28, 2016·Cell Death Discovery·Sonali RoyManobjyoti Bordoloi
Sep 2, 2015·Antimicrobial Agents and Chemotherapy·Bo WangHailong Lv
Aug 2, 2014·Asian Pacific Journal of Cancer Prevention : APJCP·Li-Xia BaiJin-Tao Wang
May 30, 2020·Environmental Toxicology and Pharmacology·Atish RayShibnath Mazumder
Oct 14, 2014·Chemical Research in Toxicology·Sarmishtha ChatterjeeShelley Bhattacharya

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