Acute and chronic effects of environmental realistic concentrations of simvastatin in danio rerio: evidences of oxidative alterations and endocrine disruptive activity

Elucidating the Effects of the Lipids Regulators Fibrates and Statins on the Health Status of Finfish Species: A Review

“…Furthermore, the authors demonstrated the potential for simvastatin to interact with other chemical environmental pollutants, possibly having synergistic effects [116]. In contrast, Rebelo et al [123] observed a significant decrease in SOD, GST and GPx, as well as thiobarbituric acid reactive substances (TBARS), in zebrafish embryos and juveniles following both acute and chronic exposures to simvastatin, indicating a reduction in antioxidant defences. In addition, significant behavioural changes were detected throughout these experiments, but no alterations in gonad development or sex determination were noted.…”

“…Therefore, the effects of this contaminant on an aquatic organism may vary greatly between species, or life stages within the same species (Table 2), but might be less severe than those observed for fibrates. ↑ and ↓ locomotion (erratic vs. purposeful swimming, distance travelled and time) depending on dose and day/night phase ↑ Cu-ZnSOD ↓ GPx, GST, TBARS [123] Abbreviations: Atorvastatin (ATV); Simvastatin (SIM); Superoxide Dismutase (SOD); Metallothionein (MT), bcl-2 associated X protein (BAX), P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), Sulfotransferase Family 2B (SULT2b); cholesterol (Chol), testosterone (T); estrogen (E); triglycerides (TG); cytochrome P450, family 3, subfamily A, polypeptide 65 (CYP3A65); cytochrome P450, family 3, subfamily A (CYP3A); cytochrome P450, family 3, subfamily A, polypeptide 27 (CYP3A27); cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A); cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1); cytochrome P450, family 51 (CYP51); Peroxisome proliferator-activated receptor alpha (PPARα); Peroxisome proliferator-activated receptor Beta (PPARβ) peroxisome proliferator-activated receptor gamma (PPARΥ); sterol regulatory element-binding protein 1 (SREBP1); sterol regulatory element-binding protein 2 (SREBP2); 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase 1 (HMGCR1); 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMGCRA); 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase 2 (HMGCR2); cytochrome oxidase (COX); citrate synthase (CS); lactate dehydrogenase (LDH); muscle RING-finer (MURF); peroxisome proliferator-activated receptor gamma coactivator 1α (pgc-1α); low-density lipoprotein receptor (LDLR); ATP-binding cassette transporter (ABC); ATP-binding cassette, subfamily B, member 4 (ABCB4); ATP-binding cassette, subfamily C, member 1 (ABCC1); ATP-binding cassette, subfamily C, member 2 (ABCC2); ATP-binding cassette, subfamily G, member 2A (ABCG2A); ethoxyresorufin-O-deethylase (EROD); glutathione S-transferases (GST); Copper (Cu); Zinc (Zn); catalase (CAT); pregnane X receptor (PXR); aryl hydrocarbon receptor (AhR); retinoic acid receptor alpha (RAR-α); retinoic acid receptor Beta (RAR-β); retinoic acid receptor alpha b (RAR-αb); recombination activating gene alpha (RAG-α); retinoid x receptor alpha a (rxrαa); retinoid x receptor alpha b (rxrαb); retinoid x receptor beta b (rxrβb); retinoid x receptor gamma a (rxrga); retinoid x receptor gamma b (rxrgb); multidrug resistance-associated protein 2 (MRP2); uridine 5 -diphospho-glucuronosyltransferase (UGT); Erythromycin-N-Demethylase (ERND); microRNA 148a (miR-148a); microRNA 148a (miR-148a); microRNA 34a (miR-34a); microRNA 34c (miR-34c); microRNA 34b (miR-34b); microRNA 27a (miR-27a); microRNA 27b (miR-27b); malondialdehyde (MDA); glutathione (GSH); Glutathione peroxidase (GPx); glucose transporter 1b (glut1b); cytochrome c oxidase subunits 4I1 (COX4I1); cytochrome c oxidase subunits 5aa (COX5aa); glyceraldehyde 3-phosphate dehydrogenase (GAPDH); medium-chain acyl-CoA dehydrogenase (ACADM); NF-E2-related factor 2 protein (Nrf2); superoxide dismutase 2 (SOD2); Alpha-glutathione S-transferase (GSTA); glutamate cysteine ligase catalytic subunit (GCLC); NAD(P)H quinone dehydrogenase 1 (NQO1); extracellular regulated protein kinase (ERK); c-Jun N-terminal kinase (JNK); and Thiobarbituric acid reactive substances (TBARS).…”