Host: The Japanese Society of Toxicology
Arsenic is an environmental toxic metalloid responsible for many human diseases and affecting many millions of people all over the world. In the present investigation, the efficacy of curcumin, a naturally occurring polyphenol against arsenic-induced cytotoxic manifestations with insights into biomolecular mechanism/s has been studied in PC12 cells. Results revealed that arsenic (10 μM) treatment in PC12 cells for 24 h induced cytotoxicity by decreasing cell viability and intracellular glutathione level and increasing lactate dehydrogenase activity and DNA fragmentation. Moreover, arsenic-induced apoptotic cell death in PC12 cells, which were confirmed from the flow cytometry results. In addition, arsenic treatment significantly down-regulated the survival proteins; mTOR, Akt, Nrf2, ERK1, Bcl-x, Xiap and up-regulated the cell-death related proteins; ULK, LC3, p53, Bax, cytochrome c, caspase 9, cleaved caspase 3 and ultimately caused autophagic and apoptotic cell death. However, pretreatment of curcumin (2.5 μM) with arsenic (10 μM) protects PC12 cells from arsenic-induced cytotoxicity by increasing cell viability, GSH level and boosting the antioxidant defense system, and limiting the LDH activity and DNA damage. Furthermore, pretreatment of curcumin with arsenic significantly inhibited arsenic-induced toxicity and cell death by reversing the expressions of proteins. Our findings suggested that curcumin showed antioxidant properties through the Nrf2 antioxidant signaling pathway and improves arsenic-induced toxicity in PC12 cells via modulating autophagy/apoptosis.
