posted on 2021-04-12, 11:03authored byHongjing Zhao, Yu Wang, Yachen Liu, Kai Yin, Dongxu Wang, Baoying Li, Hongxian Yu, Mingwei Xing
Cypermethrin
(CMN) is a man-made insecticide, and its abuse has
led to potential adverse effects, particularly in sensitive populations
such as aquatic organisms. The present study was focused on the toxic
phenotype and detoxification mechanism in grass carp (Ctenopharyngodon idella) after treatment with waterborne
CMN (0.651 μg/L) for 6 weeks in vivo or 6.392 μM for 24
h in vitro. In vivo, we describe the toxic phenotype of the liver
of grass carp in terms of pathological changes, serum transaminase
levels, oxidative stress indexes, and apoptosis rates. RNA-Seq analysis
(2 × 3 cDNA libraries) suggested a compromise of proteasome and
oxidative phosphorylation signaling pathways under CMN exposure. Thus,
these two pathways were chosen for the in vitro study, which suggested
that the CMN intoxication-induced proteasome pathway caused hepatotoxicity
in the liver cell line of grass carp (L8824 cells). Moreover, pretreatment
with MG132, a proteasome inhibitor, displayed protection against the
toxic effects of CMN by enhancing antioxidative and anti-inflammatory
capability by directly inhibiting the proteasomal degradation of nuclear
factor erythroid-2 related factor (Nrf2) and IκB-α, thus
turning on the transcription of downstream genes of Nrf2 and NF-κB,
respectively. Taken together, these results suggest proteasome activity
as a reason for CMN-induced hepatotoxicity.