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ATP-binding cassette (ABC) proteins were first recognized for their role in multidrug resistance (MDR) in chemotherapeutic treatments, which is a major impediment for the successful treatment of many forms of malignant tumors in humans. These proteins, highly conserved throughout vertebrate species, were later related to cellular detoxification and accounted as responsible for protecting aquatic organisms from xenobiotic insults in the so-called multixenobiotic resistance mechanism (MXR). In recent years, research on these proteins in aquatic species has highlighted their importance in the detoxification mechanisms in fish thus it is necessary to continue these studies. Several transporters have been pointed out as relevant in the ecotoxicological context associated to the transport of xenobiotics, such as P-glycoproteins (Pgps), multidrug resistance-associated proteins (MRPs 1-5) and breast cancer resistance associated protein (BCRP). In mammals, several nuclear receptors have been identified as mediators of phase I and II metabolizing enzymes and ABC transporters. In aquatic species, knowledge on co-regulation of the detoxification mechanism is scarce and needs to be addressed. The interaction of emergent contaminants that can act as chemosensitizers, with ABC transporters in aquatic organisms can compromise detoxification processes and have population effects and should be studied in more detail. This review intends to summarize the recent advances in research on MXR mechanisms in fish species, focusing in 1) regulation and functioning of ABC proteins; 2) cooperation with phase I and II biotransformation enzymes; and 3) ecotoxicological relevance and information on emergent pollutants with ability to modulate ABC transporters expression and activity. Several lines of evidence are clearly suggesting the important role of these transporters in detoxification mechanisms and must be further investigated in fish to underlay the mechanism to consider their use as biomarkers in environmental monitoring. [ABSTRACT FROM AUTHOR]

Background Fatty acids, a considerable fraction of lipid molecules, participate in fundamental physiological processes. They undergo activation into their corresponding CoA esters for oxidation or esterification into complex lipids (e.g. triglycerides, phospholipids and cholesterol esters), a process that is carried out by acyl-CoA synthases (ACS). Here we analyze the evolution of the gene family encoding for the long-chain acyl-CoA synthetases (Acsl) in vertebrates. Results By means of phylogenetics and comparative genomics we show that genome duplications (2R) generated the diversity of Acsl genes in extant vertebrate lineages. In the vertebrate ancestor two separate genes originated the current Acsl1/5/6 and the Acsl3/4 gene families, and the extra gene duplicates in teleosts are a consequence of the teleost specific third round of genome duplication (3R). Moreover, the diversity of Acsl family members is broader than anticipated. Our strategy uncovered a novel uncharacterized Acsl-like gene found in teleosts, spotted gar, coelacanth and possibly lamprey, which we designate Acsl2. The detailed analysis of the Acsl2 teleost gene locus strongly supports the conclusion that it corresponds to a retained 2R paralogue, lost in tetrapods. Conclusion We provide here the first evolutionary analysis of the Acsl gene family in vertebrates, showing the specific contribution of 2R/3R to the diversity of this gene family. We find also that the division of ACSL enzymes into two groups predates at least the emergence of deuterostomes. Our study indicates that genome duplications significantly contributed to the elaboration of fatty acid activation metabolism in vertebrates. [ABSTRACT FROM AUTHOR]

Abstract: In fish, some ABC transporters are implicated in a multixenobiotic resistance (MXR) mechanism to deal with the presence of xenobiotics, by effluxing them, or their metabolites, from inside the cells. These efflux transporters have been considered an integral part of cellular detoxification pathways, acting in coordination with phase I and II detoxification enzymes. However, the full characterization of this detoxification system is still incomplete, especially during the developmental stages of aquatic organisms, which are particularly sensitive periods to the presence of anthropogenic contamination. The goal of this study was to evaluate the mRNA expression dynamics of putatively important MXR proteins (ABCB1b, ABCB11, ABCC1, ABCC2 and ABCG2a) and phase I (CYP1A) and II (GSTα) biotransformation enzymes, during the embryonic and larval developments of the specie Oreochromis niloticus (Nile tilapia). Our results showed that ABCB1b, ABCC1, CYP1A and GSTα transcripts are maternally transmitted. Transcripts for ABCB11, ABCC2 and ABCG2a were only detected after the pharyngula period, which precedes a highly sensitive stage in the embryonic development, the hatching. This study has shown, for the first time, very distinct expression patterns of genes encoding for proteins involved in protection mechanisms against pollutants during the development of Nile tilapia. Moreover, the temporal pattern of gene expression suggests that increased intrinsic protection levels are required at specific developmental stages. [Copyright &y& Elsevier]

Although retinoids have been reported to be present and active in vertebrates and invertebrates, the presence of mechanisms for retinoid storage in the form of retinyl esters, a key feature to maintain whole-organism retinoid homeostasis, have been considered to date a vertebrate innovation. Here we demonstrate for the first time the presence of retinol and retinyl esters in an invertebrate lophotrochozoan species, the gastropod mollusk Osilinus lineatus. Furthermore, through a pharmacological approach consisting of intramuscular injections of different retinoid precursors, we also demonstrate that the retinol esterification pathway is active in vivo in this species. Interestingly, retinol and retinyl esters were only detected in males, suggesting a gender-specific role for these compounds in the testis. Females, although lacking detectable levels of retinol or retinyl esters, also have the biochemical capacity to esterify retinol, but at a lower rate than males. The occurrence of retinyl ester storage capacity, together with the presence in males and females of active retinoids, i.e., retinoic acid isomers, indicates that O. lineatus has a well developed retinoid system. Hence, the present data strongly suggest that the capacity to maintain retinoid homeostasis has arisen earlier in Bilateria evolution than previously thought. [ABSTRACT FROM AUTHOR]

3-Hydroxy-benzo[a]pyrene (3-OH-BaP), a toxic compound with the ability to covalently bind with the macromolecules (proteins and DNA), is one of the major phenolic metabolites of benzo[a]pyrene (BaP). The purpose of this study was to evaluate the presence of 3-OH-BaP in the bile and plasma of Nile tilapia by HPLC with fluorescence detection, after waterborne exposure to BaP (10 and 100 µg L−1). Metabolites were detected in bile and plasma, and conjugates of 3-OH-BaP (glucuronide and/or sulphate conjugates) were the majority forms in both biological fluids, glucuronide 3-OH-BaP being the main metabolite in bile. Our data suggest that extrahepatic tissues as intestine or gill are important in BaP metabolism and need to be the considered sources of metabolites released into the blood. Although, low levels of 3-OH-BaP in toxic form (free form) were detected in plasma, one cannot exclude the possibility of circulating the levels leading to adverse effects. [ABSTRACT FROM AUTHOR]

The occurrence of psychopharmaceuticals in aquatic ecosystems is a growing problem. Fluoxetine (FL) and its metabolite norfluoxetine (NF) are selective serotonin reuptake inhibitors. Although they may be potentially harmful to non-target species, available knowledge on the effects of NF is sparse, relative to FL. This study aimed at contributing to the body of knowledge about the modes-of-action (MoA) of these compounds and their underlying mechanisms eliciting hazardous effects during the early development of the teleost model zebrafish (Danio rerio). One hour post-fertilisation (hpf), embryos were exposed up to 80 hpf to these compounds at levels found in surface waters and higher (FL, 0.0015 and 0.05 µM; NF, 0.00006 and 0.0014 µM). Developmental anomalies were observed at 8, 32 and 80 hpf. Larvae were collected at 80 hpf to assess the expression of 34 genes related to FL and NF MoA and metabolism, using qPCR (quantitative reverse transcription PCR). Results showed that both compounds elicited an increased frequency of embryos exhibiting abnormal pigmentation, relative to controls. Gene expression alterations were more pronounced in FL- than in NF-exposed larvae. Cluster Analysis revealed two groups of genes discriminating between the drugs. for their marked opposing responses. Globally, downregulation of gene expression was typical of FL, whilst upregulation or no alteration was found for NF. These clusters identified were linked to the adrenergic pathway and to the retinoid and peroxisome proliferator-activated nuclear receptors. Overall, our data contradict the prevailing notion that NF is more toxic than FL and unveiled the expression levels of genes drd2b, 5-ht2c and abcc2 as possible markers of exposure to FL. [ABSTRACT FROM AUTHOR]