Effects of norfloxacin nicotinate on the early life stage of zebrafish (Danio rerio): Developmental toxicity, oxidative stress and immunotoxicity.

Norfloxacin nicotinate (NOR-N), an adduct of norfloxacin (NOR) and nicotinic acid, has been widely used for replacing NOR in animal husbandry and fishery industry. Nowadays, increasing evidences showed that NOR could pose toxic effects on fish and other aquatic organisms, but as its adduct, whether NOR-N could cause adverse effects on aquatic organisms is still unclear. To evaluate the toxic effects of NOR-N on the early life stage of zebrafish, we determined the changes in embryonic development (hatching rate, body length, malformation rate and mortality), antioxidant enzyme (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (Gpx)) activities, malondialdehyde (MDA) content and gene expression levels related to antioxidant enzymes (Cu/Zn-sod, Mn-sod, CAT and Gpx) and innate immune system (tumor necrosis factor α (TNFα), interferon (IFN), Interleukin-1 beta (IL-1ß), IL-8, CXCL-clc, CC-chemokine, lysozyme (Lzy) and complement factors (C3)) after embryonic exposure to NOR-N till 96 hpf. The results showed that NOR-N exposure could decreased the hatching rate and body length, and increased abnormality and mortality as concentration-dependent during embryonic development process. NOR-N induced oxidative stress in zebrafish larvae through increasing the contents of MDA and the activities of SOD, CAT and Gpx, as well as the mRNA levels of genes related to these antioxidant enzymes. Moreover, the expression of TNFα, IFN, IL-1ß, IL-8, CXCL-clc, CC-chemokine, Lzy and C3 genes were significantly up-regulated after exposure to high concentration (5 and/or 25 mg/L) of NOR-N till 96 hpf, indicating that the innate immune system in zebrafish larvae was disturbed by NOR-N. Overall, our results suggested that NOR-N caused development toxicity, oxidative stress and immunotoxicity on the early life stage of zebrafish. Thus, widespread application of NOR-N might pose potential ecotoxicological risk on aquatic ecosystems.

Adverse effects in Daphnia magna exposed to e-waste leachate: Assessment based on life trait changes and responses of detoxification-related genes.

The sharp increase in e-waste derived from great consumption of electronic products has become a potential global environmental challenge. Limited information is available about the potential detrimental impact of e-waste on aquatic organisms. The present study investigated the expression of detoxification-related genes and life-history parameter changes in Daphnia magna exposed to e-waste leachate, simultaneously integrating with the chemical analysis of typical pollutants from e-waste leachate. The study aims at assessing impacts of e-waste to aquatic invertebrates and providing insights into its toxic mechanisms. The results showed high concentration of heavy metals like Cu (1657.14 ± 259.3 µg g-1, DW) and persistent organic compounds like polybrominated diphenyl ethers (7831.32 ± 1273.86 ng g-1, DW) in stream sediments near e-waste dismantling areas. Chronic exposure to these pollutants can affect the growth and reproduction of D. magna, resulting in significant development retardation, decreased total egg production per female, and even smaller body size. Expression of some detoxification and reproduction-related genes including DappuHR96, CYP360a, P-gp, EcR, CYP314 and Vtg exhibited different response patterns depending on the e-waste leachate concentration. E-waste leachate may affect the expression of detoxification-related and growth and reproduction-related genes and disrupt the growth and reproduction processes of D. magna.

Paracetamol affects the expression of detoxification- and reproduction-related genes and alters the life traits of Daphnia magna.

Paracetamol (APAP) is a widely used non-steroidal anti-inflammatory drug and has been frequently detected in aquatic environment. However, limited information is provided about the toxic effects and detoxification mechanism of APAP in aquatic invertebrates. In the present study, the change of life traits of Daphnia magna (e.g., body length, growth rate and reproduction) was investigated under the chronic APAP exposure (0-5000 µg/L) for 21 day, and the effects of APAP on the expression of the detoxification- and reproduction-related genes including HR96, CYP360A8, CYP314, MRP4, P-gp, EcR and Vtg in the acute exposure (up to 96 h) were also determined. Results showed that the molting frequency, days to the first brood and days to the first egg production of D. magna were affected under the 50 µg/L concentration of APAP in the chronic exposure test. In the acute test, the transcriptional expression of HR96 was up-regulated under APAP exposure for 24 and 48 h. Similar performances were also observed in the expression of CYP360A8, CYP314, MRP4 and P-gp. However, with exposure time extended to 96 h, the induction of HR96 decreased or even reversed in some cases. It may indicate that the defense system in Daphnia is activated for a short time of exposure or becomes adaptive after longer term of exposure. APAP exposure also affected reproduction-related genes expression, which was related to the exposure time and concentration of APAP. In summary, APAP significantly affected the expression of genes associated with detoxification metabolism and altered some physiological parameters in D. magna.

Simvastatin affect the expression of detoxification-related genes and enzymes in Daphnia magna and alter its life history parameters.

Simvastatin (SV), as an hypocholesterolaemic drug, has been detected in various aquatic environment. However, limited information is available on the effects of SV on freshwater invertebrates. In the present study, we investigated the toxic effects of SV on Daphnia. magna (D. magna) through measuring the physiological changes (e.g., survival, growth rate, and reproduction) in a 21-d chronic toxicity test We also determined the expression of seven detoxification and reproduction-related genes (i.e. HR96, P-gp, CYP360A8, GST, CYP314, EcR and Vtg) and several enzymes (i.e. APND, ERND, GST and CAT) in a acute test (24 h). Results showed that high concentration (e.g. 50 µg L-1) of SV for short time exposure (e.g. 24 h) significantly induced the expression of HR96 and P-gp (e.g. up to 2.5 folds)and enzymes (e.g. increasing 4.0 folds for ERND and GST activity) in D. magna.. The long-term chronic exposure (21 days) may cause the changes of life history parameters such as decreasing total egg production number per individual and intrinsic growth rates etc. SV may act as a potential endocrine disruptor to D. magna and the reproduction parameters were more sensitive endpoints than the survival and growth for evaluating SV exposure.

New Insights on Ecosystem Mercury Cycling Revealed by Stable Isotopes of Mercury in Water Flowing from a Headwater Peatland Catchment.

Stable isotope compositions of mercury (Hg) were measured in the outlet stream and in soil cores at different landscape positions in a 9.7-ha boreal upland-peatland catchment. An acidic permanganate/persulfate digestion procedure was validated for water samples with high dissolved organic matter (DOM) concentrations through Hg spike addition analysis. We report a relatively large variation in mass-dependent fractionation (δ202Hg; from -2.12 to -1.32‰) and a smaller, but significant, variation of mass-independent fractionation (Δ199Hg; from -0.35 to -0.12‰) during two years of sampling with streamflow varying from 0.003 to 7.8 L s-1. Large variations in δ202Hg occurred only during low streamflow (<0.6 L s-1), which suggest that under high streamflow conditions a peatland lagg zone between the bog (3.0 ha) and uplands (6.7 ha) becomes the dominant source of Hg in downstream waters. Further, a binary mixing model showed that except for the spring snowmelt period, Hg in streamwater from the catchment was mainly derived from dry deposition of gaseous elemental Hg (73-95%). This study demonstrates the usefulness of Hg isotopes for tracing sources of Hg deposition, which can lead to a better understanding of the biogeochemical cycling and hydrological transport of Hg in headwater catchments.

Origin, Reactivity, and Bioavailability of Mercury in Wildfire Ash.

Wildfires are expected to become more frequent and intensive at the global scale due to climate change. Many studies have focused on the loss of mercury (Hg) from burned forests; however, little is known about the origins, concentration, reactivity, and bioavailability of Hg in residual ash materials in postfire landscapes. We examine Hg levels and reactivity in black ash (BA, low burn intensity) and white ash (WA, high burn intensity) generated from two recent northern California wildfires and document that all ash samples contained measurable, but highly variable, Hg levels ranging from 4 to 125 ng/g dry wt. ( n = 28). Stable Hg isotopic compositions measured in select ash samples suggest that most Hg in wildfire ash is derived from vegetation. Ash samples had a highly variable fraction of Hg in recalcitrant forms (0-75%), and this recalcitrant Hg pool appears to be associated with the black carbon fraction in ash. Both BA and WA were found to strongly sequester aqueous inorganic Hg but not gaseous elemental Hg under controlled conditions. During anoxic ash incubation with natural surface water, we find that Hg in most ash samples had a minimal release and low methylation potential. Thus, the formation of wildfire ash can sequester Hg into relatively nonbioavailable forms, attenuating the potentially adverse effects of Hg erosion and transport to aquatic environments along with eroded wildfire ash.

Response of PXR signaling pathway to simvastatin exposure in mosquitofish (Gambusia affinis) and its histological changes.

As a widely used lipid lowering agent, simvastatin recently has been frequently detected in aquatic environment and the potential adverse effects from simvastatin exposure to non-target organisms such as fish is worthy of more attention. The aim of this study was to reveal the responses of detoxification system in fish to simvastatin exposure. In this investigation a ubiquitous small freshwater fish, mosquito fish (Gambusia affinis), was employed as test organism, and the transcriptional expression of nucleus transcriptional factor pregnane X receptor (PXR) and its downstream genes, including P-glycoprotein (P-gp), cytochrome 3A (CYP3A), multidrug resistance protein 2 (MRP2), UDP-glucuronosyl transferase (UGT) in mosquito fish were investigated by qRT-PCR methods under the exposure of concentrations of simvastatin (0.5 µg L-1, 5 µg L-1, 50 µgL-1, 500 µg L-1) for 24 h, 72 h and 168 h. The related enzyme activity (Erythromycin-N-Demethylase, ERND), the protein expression of PXR and the histological changes of liver tissues in fish were also determined via west blotting and transmission electron microscope approaches in the same conditions. Results showed that the mRNA expression of PXR, CYP3A and P-gp showed significantly changes under simvastatin exposure, exhibiting an obvious time/dose-effect relationship with the prolong of exposure time. ERND activity also showed time-effect at 24 h, and western blotting showed PXR protein displaying a dose-effect relationship to some extent. Hepatocyte cellular of mosquito fish exposed to simvastatin (5 µg L-1, 168 h) exhibited obvious histological changes in form of swelling, incomplete fragmentary structure etc. Overall, simvastatin altered the expression of PXR signaling pathway and subsequently bring about changes in high-levels of mosquito fish.

Heavy Metal Contamination in the Cultivated Oyster Crassostrea rivularis and Associated Health Risks from a Typical Mariculture Zone in the South China Sea.

With the rapid development of mariculture in potentially contaminated regions in China and the world, food safety, is a growing concern. To evaluate heavy metals and their associated health risks in the cultivated oyster Crassostrea rivularis, the concentrations of heavy metals (Cd, Cr, Pb, Zn) in oysters and water/sediment were examined in a typical mariculture environment (Kaozhou Bay, South China Sea). Trends in the seasonal dynamics of heavy metals in oysters revealed a potential synergistic effects among the concentrations of Cd, Cr, and Zn; trends associated with Pb were less clear, although the ability of oysters to bioaccumulate and depurate Pb was excellent. Bioconcentration factors (BCF) indicated that C. rivularis has a strong ability to accumulate heavy metals, and the BCF was the highest for Zn (2.32 × 105), followed by Cd (6.84 × 104), Pb (2.77 × 104) and Cr (1.23 × 103) through the four seasons. Results showed that Cd concentrations in oysters could pose a risk to human health (HQ > 1). This study, therefore, suggests that there are potential human health risks due to heavy metal exposure through the consumption of C. rivularis from mariculture zones in South China Sea.

Toxic assessment of the leachates of paddy soils and river sediments from e-waste dismantling sites to microalga, Pseudokirchneriella subcapitata.

The potential adverse effects of e-waste recycling activity on environment are getting increasing concern. In this work, a model alga, Pseudokirchneriella subcapitata, was employed to assess the toxic effects of the leachates of paddy soils and river sediments collected from e-waste dismantling sites. Chemical analysis of the paddy soils and river sediments and their leachates were carried out and the growth rate, chlorophyll a fluorescence and anti-oxidative systems of the alga were measured. Results showed that two leachates decreased the amount of PSII active reaction centers and affected photosynthesis performance, interfered with chlorophyll synthesis and inhibited algal growth. Some chemical pollutants in the sediments and soils such as polybrominated diphenyl ethers (PBDEs) and metals derived from e-waste recycling activity may impose oxidative stress on algae and affect the activity of anti-oxidative enzymes such as GST, SOD, CAT and APX. The leachates of both river sediments and paddy soils are potentially toxic to the primary producers, P. subcapitata and the leachate from sediments was more deleterious than that from soils.

Effects of norfloxacin on hepatic genes expression of P450 isoforms (CYP1A and CYP3A), GST and P-glycoprotein (P-gp) in Swordtail fish (Xiphophorus Helleri).

The presence of antibiotics including norfloxacin in the aquatic environment may cause adverse effects in non-target organisms. But the toxic mechanisms of fluoroquinolone to fish species are still not completely elucidated. Thus, it is essential to investigate the response of fish to the exposure of fluoroquinolone at molecular or cellular level for better and earlier prediction of these environmental pollutants toxicity. The sub-chronic toxic effects of norfloxacin (NOR) on swordtail fish (Xiphophoru s helleri) were investigated by measuring mRNA expression of cytochrome P450 1A (CYP1A), cytochrome P450 3A (CYP3A), glutathione S-transferase (GST) and P-glycoprotein (P-gp) and their corresponding enzyme activities (including ethoxyresorufin O-deethylase, erythromycin N-demethylase and GST. Results showed that NOR significantly affected the expression of CYP1A, CYP3A, GST and P-gp genes in swordtails. The gene expressions were more responsive to NOR exposure than their corresponding enzyme activities. Moreover, sexual differences were found in gene expression and enzyme activities of swordtails exposed to NOR. Females displayed more dramatic changes than males. The study further demonstrated that the combined biochemical and molecular parameters were considered as useful biomarkers to improve our understanding of potential ecotoxicological risks of NOR exposure to aquatic organisms.

Toxic effects of environmentally relevant concentrations of naproxen exposure on Daphnia magna including antioxidant system, development, and reproduction.

Naproxen (NPX) is one of common non-prescription non-steroidal anti-inflammatory drugs (NSAIDs) which is widely detected in aquatic environments worldwide due to its high usage and low degradation. NPX exerts anti-inflammatory and analgesic pharmacological effects through the inhibition of prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase (COX). Given its evolutionarily relatively conserved biological functions, the potential toxic effects of NPX on non-target aquatic organisms deserve more attention. However, the ecotoxicological studies of NPX mainly focused on its acute toxic effects under higher concentrations while the chronic toxic effects under realistic concentrations exposure, especially for the underlying molecular mechanisms still remain unclear. In the present study, Daphnia magna, being widely distributed in freshwater aquatic environments, was selected to investigate the toxic effects of environmentally relevant concentrations of NPX via determining the response of the Nrf2/Keap1 signaling pathway-mediated antioxidant system in acute exposure, as well as the changes in life-history traits, such as growth, reproduction, and behavior in chronic exposure. The results showed that the short-term exposure to NPX (24 h and 48 h) suppressed ptgs2 expression while activating Nrf2/Keap1 signaling pathway and its downstream antioxidant genes (ho-1, sod, cat and trxr). However, with prolonged exposure to 96 h, the opposite performance was observed, the accumulation of malondialdehyde (MDA) indicated that D. magna suffered from severe oxidative stress. To maintain homeostasis, the exposed organism may trigger ferroptosis and apoptosis processes with the help of Silent mating type information regulation 2 homologs (SIRTs). The long-term chronic exposure to NPX (21 days) caused toxic effects on D. magna at the individual and population levels, including growth, reproduction and behavior, which may be closely related to the oxidative stress induced by the drug. The present study suggested that more attention should be paid to the ecological risk assessment of NSAIDs including NPX on aquatic non-target organisms.

Response of lipid metabolism, energy supply, and cell fate in yellowstripe goby (Mugilogobius chulae) exposed to environmentally relevant concentrations atorvastatin.

The usage of typical pharmaceuticals and personal care products (PPCPs) such as cardiovascular and lipid-modulating drugs in clinical care accounts for the largest share of pharmaceutical consumption in most countries. Atorvastatin (ATV), one of the most commonly used lipid-lowering drugs, is frequently detected with lower concentrations in aquatic environments owing to its wide application, low removal, and degradation rates. However, the adverse effects of ATV on non-target aquatic organisms, especially the molecular mechanisms behind the toxic effects, still remain unclear. Therefore, this study investigated the potentially toxic effects of ATV exposure (including environmental concentrations) on yellowstripe goby (Mugilogobius chulae) and addressed the multi-dimensional responses. The results showed that ATV caused typical hepatotoxicity to M. chulae. ATV interfered with lipid metabolism by blocking fatty acid ß-oxidation and led to the over-consumption of lipids. Thus, the exposed organism was obliged to alter the energy supply patterns and substrates utilization pathways to keep the normal energy supply. In addition, the higher concentration of ATV exposure caused oxidative stress to the organism. Subsequently, M. chulae triggered the autophagy and apoptosis processes with the help of key stress-related transcriptional regulators FOXOs and Sestrins to degrade the damaged organelles and proteins to maintain intracellular homeostasis.

Atorvastatin causes developmental and behavioral toxicity in yellowstripe goby (Mugilogobius chulae) embryos/larvae via disrupting lipid metabolism and autophagy processes.

Atorvastatin (ATV) is one of the most commonly prescribed lipid-lowering drugs detected frequently in the environment due to its high use and low degradation rate. However, the toxic effects of residual ATV in the aquatic environment on non-target organisms and its toxic mechanisms are still largely unknown. In the present study, embryos of a native estuarine benthic fish, Mugilogobius chulae, were employed to investigate the developmental and behavioral toxic effects of ATV including environmentally relevant concentrations. The aim of this study was to provide a scientific basis for ecological risk assessment of ATV in the aquatic environment by investigating the changes of biological endpoints at multiple levels in M. chulae embryos/larvae. The results showed that ATV had significantly lethal and teratogenic effects on M. chulae embryos/larvae and caused abnormal changes in developmental parameters including hatch rate, body length, heart rate, and spontaneous movement. ATV exposure caused oxidative stress in M. chulae embryos/larvae subsequently inhibited autophagy and activated apoptosis, leading to abnormal developmental processes and behavioral changes in M. chulae embryos/larvae. The disruptions of lipid metabolism, autophagy, and apoptosis in M. chulae embryos/larvae caused by ATV exposure may pose a potential ecological risk at the population level.

Aspirin exposure coupled with hypoxia interferes energy metabolism, antioxidant and autophagic processes and causes liver injury in estuarine goby Mugilogobius chulae.

Toxicity assessments of pollutants often overlook the impact of environmental factors like hypoxia, which can alter chemical toxicity with unexpected consequences. In this study, Mugilogobius chulae, an estuarine fish, was used to investigate the effects of hypoxia (H), aspirin (ASA), and their combination (H_ASA) exposure over 24, 72, and 168 h. We employed RNA-seq analysis, expression of key gene expression profiling, enzymatic activity assays, and histopathological and ultrastructural examinations of liver tissue to explore the effects and mechanisms of ASA-coupled hypoxia exposure in fish. Results showed that glycolysis was inhibited, and lipolysis was enhanced in ASA/H_ASA groups. The PPAR signaling pathway was activated, increasing fatty acid ß-oxidation and lipophagy to mitigate energy crisis. Both ASA and H_ASA exposures induced p53 expression and inhibited the TOR pathway to combat environmental stress. However, a greater energy demand and heightened sensitivity to ASA were observed in H_ASA compared to ASA exposure. Disruptions in energy and detoxification pathways led to increased stress responses, including enhanced antioxidant activities, autophagy, and apoptotic events, as observed in organelle structures. Overall, sub-chronic H_ASA exposure caused liver injury in M. chulae by affecting energy metabolism, antioxidant regulation, and autophagy processes. This study highlights the influence of hypoxia on ASA toxicity in fish, providing valuable insights for ecological risk assessment of NSAIDs.

Advanced oxidation kinetics and mechanism of preservative propylparaben degradation in aqueous suspension of TiO2 and risk assessment of its degradation products.

The absolute kinetic rate constants of propylparaben (PPB) in water with different free radicals were investigated, and it was found that both hydroxyl radicals (HO(•)) and hydrated electrons could rapidly react with PPB. The advanced oxidation kinetics and mechanisms of PPB were investigated using photocatalytic process as a model technology, and the degradation was found to be a pseudo-first-order model. Oxidative species, particularly HO(•), were the most important reactive oxygen species mediating photocatalytic degradation of PPB, and PPB degradation was found to be significantly affected by pH because it was controlled by the radical reaction mechanism and was postulated to occur primarily via HO(•)-addition or H-abstraction reactions on the basis of pulse radiolysis measurements and observed reaction products. To investigate potential risk of PPB to humans and aqueous organisms, the estrogenic assays and bioassays were performed using 100 µM PPB solution degraded by photocatalysis at specific intervals. The estrogenic activity decreased as PPB was degraded, while the acute toxicity at three trophic levels first increased slowly and then decreased rapidly as the total organic carbon decreased during photocatalytic degradation.

Toxic effects of triclosan on the detoxification system and breeding of Daphnia magna.

The toxic effects of different concentrations of Triclosan (TCS) (1-128 µg/L) on Daphnia magna (D. magna) were investigated by acute (48 h) and chronic (21-day) toxicity tests. The response of antioxidase system and Phase I metabolism process of D. magna exposed to TCS were investigated by measuring a series of biomarkers including glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), 7-ethoxyresorufin O-deethylase (EROD), Erythromycin N-demethylase (ERND) and Aminopyrine N-demethylase (APND). The 48 h LC50 of TCS was 330 µg/L for D. magna. In the chronic test, total number of neonates per female, body length and the intrinsic rate of natural increase (r) of D. magna increased at the low exposure concentrations (1-16 µg/L) and decreased at the high concentrations (64-128 µg/L), while the total number of molting per adult decreased continually. The GST and CAT activities showed no significant increase in all treatments, and SOD activities were induced after 24-h exposure and inhibited after 48-h exposure at 4-128 µg/L of concentrations. The MDA content increased after 6-h exposure but decreased after 48-h exposure at 4-128 µg/L. EROD activities initially increased after 6-h exposure, but decreased after 24 and 48-h exposure, ERND and APND activities showed a similar temporal pattern among different treatments groups. SOD, MDA and APND were sensitive to TCS, thus they are suitable as potential biomarkers for the exposure to TCS.

Acetaminophen exposure alters the DNA methylation pattern of Mugilogobius chulae, along with the changes in the Nrf2-Keap1 signaling pathway.

DNA methylation can dynamically regulate multiple physiological processes in organisms in response to changes of the external environment. The effects of acetaminophen (APAP) on DNA methylation in aquatic organisms and its toxic mechanisms is an interesting issue. In the present study, Mugilogobius chulae (Approximately 225 individual), a small benthic native fish, were employed to assess the toxic effects of APAP-exposure on non-target organisms. First, under APAP exposure (0.5 µg/L and 500 µg/L) for 168 h, 17,488 and 14,458 differentially methylated regions (DMRs) were identified in liver of M. chulae, respectively, which were involved in energy metabolism, signaling transduction, and cellular processes etc. The modification of lipid metabolism by DNA methylation was particularly prominent and the increased fat vacuoles in the sections were observed. Some key nodes associated with oxidative stress and detoxification such as Kelch-1ike ECH-associated protein l (Keap1) and fumarate hydratase (FH) were modified by DNA methylation. Meanwhile, changes in DNA methyltransferase and Nrf2-Keap1 signaling pathways at different concentrations of APAP (0.5 µg/L, 5 µg/L, 50 µg/L and 500 µg/L) for different time (24 h and 168 h) were addressed at the transcriptional level. Results showed that ten eleven translocation enzymes 2 (TET2) transcript expression was upregulated 5.7-folds after being exposed to 500 µg/L APAP for 168 h, indicating the urgent need for active demethylation in the exposed organism. The elevated DNA methylation levels of Keap1 led to repression of its transcriptional expression so as to promote recovery or reactivation of Nrf2, which displayed negatively relationship with Keap1 gene. Meanwhile, P62 was significantly positively correlated with Nrf2. Downstream genes in the Nrf2 signaling pathway changed synergistically except for Trx2, in which GST and UGT were highly significantly upregulated. This work illustrated that APAP exposure altered the DNA methylation processes, together with the Nrf2-Keap1 signaling pathway, and affected the stress responses of M. chulae to pharmaceuticals exposure.

Hypoxia aggravates the burden of yellowstripe goby (Mugilogobius chulae) under atorvastatin exposure.

In the present study, an estuarine benthic fish, Mugilogobius chulae (M. chulae), was exposed to hypoxia, atorvastatin (ATV), a highly used and widely detected lipid-lowering drug in aquatic environment, and the combination of hypoxia and ATV for 7 days, respectively, so as to address and compare the effects of the combination of hypoxia and ATV exposure on M. chulae. The results showed that lipid metabolism in M. chulae was greatly affected: lipid synthesis was blocked and catabolism was enhanced, exhibiting that lipids content were heavily depleted. The combined exposure of hypoxia and ATV caused oxidative stress and induced massive inflammatory response in the liver of M. chulae. Signaling pathways involving in energy metabolism and redox responses regulated by key factors such as HIF, PPAR, p53 and sirt1 play important regulatory roles in hypoxia-ATV stress. Critically, we found that the response of M. chulae to ATV was more sensitive under hypoxia than normoxia. ATV exposure to aquatic non-target organisms under hypoxic conditions may make a great impact on the detoxification and energy metabolism, especially lipid metabolism, and aggravate the oxidative pressure of the exposed organisms.

Effects of atorvastatin on the Sirtuin/PXR signaling pathway in Mugilogobius chulae.

Atorvastatin (ATV) is a hypolipidemic drug widely detected in the aquatic environment. Nevertheless, limited information is provided about the toxic effects of ATV on estuary or coastal species and the underlying mechanisms. In the present study, the responses of genes expression in pregnane X receptor (PXR) signaling pathway and enzymatic activities in the liver of the estuarine benthic fish (Mugilogobius chulae) were investigated under acute and sub-chronic ATV exposure. Results showed that PXR was significantly inhibited in the highest exposure concentration of ATV for a shorter time (24 h, 500 µg L-1) but induced in a lower concentration (72 h, 5 µg L-1). The downstream genes in PXR signaling pathway such as CYP3A, SULT, UGT, and GST showed similar trends to PXR. P-gp and MRP1 were repressed in most treatments. GCLC associated with GSH synthesis was mostly induced under ATV exposure for a long time (168 h), suggesting that reactive oxygen species (ROS) were generated under ATV exposure. Similarly, GST and SOD enzymatic activities significantly increased in most exposure treatments. Under ATV exposure, SIRT1 and SIRT2 displayed induction to some extent in most treatments, suggesting that SIRTs may affect PXR expression by regulating the acetylation levels of PXR. The investigation demonstrated that ATV exposure affected the expression of the Sirtuin/PXR signaling pathway, thus further interfered adaption of M. chulae to the environment.

Physiological responses of three marine microalgae exposed to cypermethrin.

The effects of cypermethrin on physiological responses of three typical marine microalgal species Skeletonema costatum (Bacillariophyceae), Scrippsiella trochoidea (Dinophyceae), and Chattonella marina (Raphidophyceae), were investigated by 96-h growth tests in a batch-culture system. The 96-h median inhibition concentrations (IC(50)) were 71.4, 205, and 191 µg L(-1) for S. costatum, S. trochoidea, and C. marina, respectively. Quick and significant physiological responses occurred when algal cells were exposed to cypermethrin, and all biochemical parameters varied significantly within 6- or 12-h exposure. Cypermethrin affected algal growth, protein content, and superoxide dismutase (SOD) activity by stimulation at low concentrations (1, 5 µg L(-1)) and inhibition at high concentrations (>50 µg L(-1)). A general increase in malondialdehyde (MDA) level was observed in all test groups, which suggested that the toxic effects of cypermethrin were probably exerted through free radical generation. These results suggest that the activation of SOD and promotion of protein at early exposure are important to counteract the oxidative stress induced by cypermethrin, and the inactivation of SOD may be crucial to the growth inhibition of microalgae by cypermethrin.