TY - JOUR
T1 - Low dose of arsenic trioxide triggers oxidative stress in zebrafish brain
T2 - Expression of antioxidant genes
AU - Sarkar, Shuvasree
AU - Mukherjee, Sandip
AU - Chattopadhyay, Ansuman
AU - Bhattacharya, Shelley
PY - 2014/9
Y1 - 2014/9
N2 - Occurrence of arsenic in the aquatic environment of West Bengal (India), Bangladesh and other countries are of immediate environmental concern. In the present study, zebrafish (Danio rerio) was used as a model to investigate oxidative stress related enzyme activities and expression of antioxidant genes in the brain to 50·g/L arsenic trioxide for 90 days. In treated fish, generation of reactive oxygen species (ROS), malondialdehyde (MDA) and conjugated diene (CD) showed a triphasic response attaining a peak at the end of the exposure. In addition, a gradual increase in GSH level was noted until 60 days and at 90 days, a sudden fall was recorded which heightened arsenic toxicity. However, GSH level does not correlate well with the glutathione reductase (GR) activity. Generation of ROS in zebrafish brain due to As2O3 exposure was further evidenced by significant alteration of glutathione peroxidase (GPx) and catalase (CAT) activity, which converts H2O2 to water and helps in detoxication. Moreover, enhanced mRNA level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in As2O3 exposed zebrafish indicates a protective role of Nrf2. kelch-like ECH-associated protein 1 (Keap1), a negative regulator of Nrf2, inversely correlates with the mRNA expression of Nrf2. As2O3 induced toxicity was also validated by the alteration in NRF2 and NRF2 dependent expression of proteins such as heme oxygenase1 (HO1) and NAD(P)H dehydrogenase quinone1 (NQO1). The mRNA expression of glutathione peroxidase (Gpx1), catalase (Cat), manganese superoxide dismutase (Mn-Sod), copper/zinc superoxide dismutase (Cu/Zn Sod) and cytochrome c oxidase1 (Cox1) were also up regulated. The expression of uncoupling protein 2 (Ucp2), an important mitochondrial enzyme was also subdued in arsenic exposed zebrafish. The oxidative stress induced by arsenic also cause reduced mRNA expression of B-cell lymphoma 2 (Bcl2) present in the inner mitochondrial membrane and thereby indicating onset of apoptosis in treated fish. It is concluded that even a low dose of arsenic trioxide is toxic enough to induce significant oxidative stress in zebrafish brain.
AB - Occurrence of arsenic in the aquatic environment of West Bengal (India), Bangladesh and other countries are of immediate environmental concern. In the present study, zebrafish (Danio rerio) was used as a model to investigate oxidative stress related enzyme activities and expression of antioxidant genes in the brain to 50·g/L arsenic trioxide for 90 days. In treated fish, generation of reactive oxygen species (ROS), malondialdehyde (MDA) and conjugated diene (CD) showed a triphasic response attaining a peak at the end of the exposure. In addition, a gradual increase in GSH level was noted until 60 days and at 90 days, a sudden fall was recorded which heightened arsenic toxicity. However, GSH level does not correlate well with the glutathione reductase (GR) activity. Generation of ROS in zebrafish brain due to As2O3 exposure was further evidenced by significant alteration of glutathione peroxidase (GPx) and catalase (CAT) activity, which converts H2O2 to water and helps in detoxication. Moreover, enhanced mRNA level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in As2O3 exposed zebrafish indicates a protective role of Nrf2. kelch-like ECH-associated protein 1 (Keap1), a negative regulator of Nrf2, inversely correlates with the mRNA expression of Nrf2. As2O3 induced toxicity was also validated by the alteration in NRF2 and NRF2 dependent expression of proteins such as heme oxygenase1 (HO1) and NAD(P)H dehydrogenase quinone1 (NQO1). The mRNA expression of glutathione peroxidase (Gpx1), catalase (Cat), manganese superoxide dismutase (Mn-Sod), copper/zinc superoxide dismutase (Cu/Zn Sod) and cytochrome c oxidase1 (Cox1) were also up regulated. The expression of uncoupling protein 2 (Ucp2), an important mitochondrial enzyme was also subdued in arsenic exposed zebrafish. The oxidative stress induced by arsenic also cause reduced mRNA expression of B-cell lymphoma 2 (Bcl2) present in the inner mitochondrial membrane and thereby indicating onset of apoptosis in treated fish. It is concluded that even a low dose of arsenic trioxide is toxic enough to induce significant oxidative stress in zebrafish brain.
KW - Arsenic trioxide
KW - Brain
KW - Low dose
KW - MRNA expression
KW - Oxidative stress
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=84901781966&partnerID=8YFLogxK
U2 - 10.1016/j.ecoenv.2014.05.012
DO - 10.1016/j.ecoenv.2014.05.012
M3 - Article
C2 - 24905690
AN - SCOPUS:84901781966
SN - 0147-6513
VL - 107
SP - 1
EP - 8
JO - Ecotoxicology and Environmental Safety
JF - Ecotoxicology and Environmental Safety
ER -