Simvastatin effects on detoxification mechanisms in Danio rerio embryos

Cunha, V and Santos, MM and Moradas-Ferreira, P and Ferreira, Marta (2016) Simvastatin effects on detoxification mechanisms in Danio rerio embryos. Environmental Science and Pollution Research, 23 (11). pp. 10615-10629. ISSN 0944-1344

PDF - Published Version Restricted to Repository staff only Download (928kB) | Request a copy

Abstract

The transcription and protein activity of defence
mechanisms such as ABC transporters, phase I and II of cellular
detoxification and antioxidant enzymes can be altered in
the presence of emerging contaminants such as pharmaceuticals
impacting the overall detoxification mechanism. The
present work aimed to characterise the effects of simvastatin
on the detoxification mechanisms of embryonic stages of
Danio rerio. In a first approach, constitutive transcription of
key genes involved in detoxification was determined.
Embryos were collected at different developmental stages,
and transcription patterns of genes coding for ABC
transporters, phase I and II and oxidative stress were analysed.
With exception of abcc2, all genes seem to be from maternal
transfer (0–2 hpf). Embryos were then exposed to different
concentrations of simvastatin (5 and 50 μg/L), verapamil
and MK571 (10 μM; ABC protein inhibitors) and a combination
of simvastatin and ABC inhibitors. mRNA expression
levels of abcb4, abcc1, abcc2, abcg2, cyp1a, cyp3a65, gst,
sod, cat was evaluated. Accumulation assays tomeasure ABC
proteins activity and activity of EROD, GST, CAT and Cu/
ZnSOD, were also undertaken. Simvastatin acted as a weak
inhibitor of ABC proteins and increased EROD and GST activity,
whereas Cu/ZnSOD and CAT activity were decreased.
Simvastatin up-regulated abcb4 and cyp3a65 transcription
(both concentrations), as well as abcc1 and abcc2 at
50 μg/L, and down-regulated gst, sod, cat at 5 μg/L. In conclusion,
our data revealed the interaction of simvastatin with
detoxification mechanisms highlighting the importance of
monitoring the presence of this emerging contaminant in
aquatic environments.

Item Type:	Journal Article
Subjects:	Q Science > Q Science (General)
Divisions:	Faculty of Science, Technology and Environment (FSTE) > School of Marine Studies
Depositing User:	Marta Ferreira
Date Deposited:	19 Sep 2016 02:09
Last Modified:	19 Sep 2016 02:09
URI:	https://repository.usp.ac.fj/id/eprint/8883

Actions (login required)

View Item