Zinc protects against arsenic-induced apoptosis in a neuronal cell line, measured by DEVD-caspase activity.
Acute and chronic arsenic exposure results in toxicity in humans and causes many neurological and other manifestations. For the first time the present study reports that zinc decreases arsenic-induced apoptosis and also confirms a single report of apoptosis induced by arsenic in a neuronal cell line. Apoptosis measured by DEVD-caspase activity peaked between 10 microM and 20 microM of arsenic trioxide. Higher concentrations of arsenic up to 40 microM caused increasing cell death with diminishing DEVD-caspase activity. The beneficial effect of zinc was proportional to its concentration with a significant decrease in arsenic-induced DEVD-caspase activity at 50 microM and 75 microM zinc (P < 0.05). This finding may be of therapeutic benefit in people suffering from chronic exposure to arsenic from natural sources, a global problem especially relevant to millions of people on the Indian subcontinent.
Milton
Austin Graham
AG
Department of Medicine, The Queen Elizabeth Hospital, Woodville, South Australia.
Zalewski
Peter David
PD
Ratnaike
Ranjit Nihal
RN
D000818:Animals; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D020169:Caspases / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000378:metabolism; D010087:Oxides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010641:Phenotype; D012978:Sodium Oxybate / Q000494:pharmacology; D013997:Time Factors; D015032:Zinc / Q000737:chemistry*; D019287:Zinc Sulfate / Q000494:pharmacology
D001152:Arsenicals; D004791:Enzyme Inhibitors; D010087:Oxides; D019287:Zinc Sulfate; D012978:Sodium Oxybate; D020169:Caspases; D015032:Zinc; D000077237:Arsenic Trioxide