Kitima Srisanga. The effects of astaxanthin to rescue the cytotoxic of paraoxon ethyl in human hematopoietic cells. Master's Degree(Bioclinical Sciences). Thammasat University. Thammasat University Library. : Thammasat University, 2017.
The effects of astaxanthin to rescue the cytotoxic of paraoxon ethyl in human hematopoietic cells
Abstract:
Parathion ethyl is widely organophosphate (OPs) that has been used in Thai agriculture. This compound has cytotoxic effects in many tissues especially brain, liver and blood circulation. The inhibition of acetylcholinesterase enzyme and induction of oxidative stress are dramatically toxification of parathion ethyl in animal and human. Since our cells have alternative molecular mechanism for eliminating the oxidative stress by the modulation of antioxidative pathway. However, the imbalanced producing ROS from OPs become a deleterious effect. Many antioxidant compounds have been introduced to attenuate the oxidative stress and toxification of OPs both in vitro and in vivo which have been addressed in various responses and effectiveness. Astaxanthin is believed as one strong antioxidant that found in Haematococcus pluvialis, red yeast Phaffia rhodozyma, and marine creatures. In this study, we elucidate the intracellular defense of astaxanthin on the reduction of paraoxon ethyl induced cytotoxic in human hematopoietic cell line (K562). Our data suggested the IC50 of paraoxon ethyl was 1.533 mM, while the astaxanthin couldnt make any toxicity to K562 cells. The co-treatment of astaxanthin with paraoxon ethyl presented the increasing cell viability and decreased the number of apoptotic cell. The ROS level identification in paraoxon ethyl was increased but slightly reduced in the combination with astaxanthin. Here, the molecular target of astaxanthin for restoring cell survival has been demonstrated on SIRT1 and FOXO3 expression. Interestingly, astaxanthin has ability to induce and restore SIRT1 and FOXO3 protein expression in co-treatment. Nevertheless, SIRT1 and FOXO3 expression are strongly diminished during paraoxon ethyl treatment. Moreover, the exclusion of FOXO3 from nucleus to cytosol under paraoxon ethyl could be observed but its sequestration of FOXO3 into the nucleus has been exhibited under astaxanthin and its co-treated by immunofluorescence assay. These data suggested that astaxanthin could rescue K562 cell survival under paraoxon ethyl induced oxidative stress by recovering the SIRT1 and FOXO3 expression and promote FOXO3 localization into the nucleus for promoting cell survival
Thammasat University. Thammasat University Library