authors pointed to the possibility that unspecific serum cholinesterases, present in the
blood of the fish, may have been overexpressed as a consequence of paracetamol
exposure. However, it is important to point that despite the type of interaction
(inhibition or enhancement) in some cases, paracetamol seems to disturb the correct
functioning of the central nervous system, affecting behavior. A conjugation of
biochemical, developmental, behavioral, and epigenetic effects in the freshwater
model fish Danio rerio after paracetamol exposure was reported by Nogueira et al.
[70]. Paracetamol exposure resulted in the increase of embryos with deformations, in
an increase in the locomotor activity, increase in DNA methylation (especially
around the head and near the eyes of exposed embryos), increase in acetylcholinesterase activity, and higher levels of catalase, glutathione peroxidase, and glutathioneS-transferases. This set of results evidences the oxidative nature of the reported
alterations and the onset of epigenetic alterations never before reported, along with a
potential neurotoxicity indication that may have been reflected in altered behavioral
traits. This is a highly comprehensive set of results that unequivocally shows the
multilevel toxicity exerted by paracetamol on fish, with the impairment of several
key functions with putative relationships among them.
2 Conclusions
The text above corresponds to a thorough selection of scientific data that shows the
involvement of paracetamol in a large number of biochemical, metabolic, and
cellular processes, whose impairment or modification may result in significant
adverse effects to exposed organisms. Much of the cited studies were undertaken
exposing aquatic organisms of different taxa and habitat to low, realistic levels of
paracetamol, which allows interpreting the toxicological data as ecologically relevant. In some cases, known mechanisms of toxic action were observed and/or
inferred from the measured alterations; in other situations, it is possible to assume
that some effects may happen as a result (or modulated by) of others. Considering the
entire alignment of studies, it becomes clear that paracetamol poses pertinent
ecotoxicological concerns, even in low already reported levels in the wild, usually
connected to its capacity of altering the redox balance of cells. However, its effects
are not confined to oxidative stress, antioxidant defenses, and peroxidative damage;
since other traits were shown to be involved as well, including histological development, tissue regeneration, embryogenesis and development, metabolism, and
neurotoxicity and behavior. We can now conclude that despite the ever increasing
number of studies, published toxicological data, and covered scientific areas, paracetamol is still an ecotoxicological challenge for years to come.
Acknowledgments Bruno Nunes is hired by “ECO-R-pharmplast - Ecotoxicity of realistic combinations of pharmaceutical drugs and microplastics in marine ecosystems,” Fundação para a
Ciência e a Tecnologia, FCT (reference POCI-01-0145-FEDER-029203). Thanks are also due to
140
B. Nunes
blood of the fish, may have been overexpressed as a consequence of paracetamol
exposure. However, it is important to point that despite the type of interaction
(inhibition or enhancement) in some cases, paracetamol seems to disturb the correct
functioning of the central nervous system, affecting behavior. A conjugation of
biochemical, developmental, behavioral, and epigenetic effects in the freshwater
model fish Danio rerio after paracetamol exposure was reported by Nogueira et al.
[70]. Paracetamol exposure resulted in the increase of embryos with deformations, in
an increase in the locomotor activity, increase in DNA methylation (especially
around the head and near the eyes of exposed embryos), increase in acetylcholinesterase activity, and higher levels of catalase, glutathione peroxidase, and glutathioneS-transferases. This set of results evidences the oxidative nature of the reported
alterations and the onset of epigenetic alterations never before reported, along with a
potential neurotoxicity indication that may have been reflected in altered behavioral
traits. This is a highly comprehensive set of results that unequivocally shows the
multilevel toxicity exerted by paracetamol on fish, with the impairment of several
key functions with putative relationships among them.
2 Conclusions
The text above corresponds to a thorough selection of scientific data that shows the
involvement of paracetamol in a large number of biochemical, metabolic, and
cellular processes, whose impairment or modification may result in significant
adverse effects to exposed organisms. Much of the cited studies were undertaken
exposing aquatic organisms of different taxa and habitat to low, realistic levels of
paracetamol, which allows interpreting the toxicological data as ecologically relevant. In some cases, known mechanisms of toxic action were observed and/or
inferred from the measured alterations; in other situations, it is possible to assume
that some effects may happen as a result (or modulated by) of others. Considering the
entire alignment of studies, it becomes clear that paracetamol poses pertinent
ecotoxicological concerns, even in low already reported levels in the wild, usually
connected to its capacity of altering the redox balance of cells. However, its effects
are not confined to oxidative stress, antioxidant defenses, and peroxidative damage;
since other traits were shown to be involved as well, including histological development, tissue regeneration, embryogenesis and development, metabolism, and
neurotoxicity and behavior. We can now conclude that despite the ever increasing
number of studies, published toxicological data, and covered scientific areas, paracetamol is still an ecotoxicological challenge for years to come.
Acknowledgments Bruno Nunes is hired by “ECO-R-pharmplast - Ecotoxicity of realistic combinations of pharmaceutical drugs and microplastics in marine ecosystems,” Fundação para a
Ciência e a Tecnologia, FCT (reference POCI-01-0145-FEDER-029203). Thanks are also due to
140
B. Nunes