Guanghua Lu

Occurrence, bioaccumulation and risk assessment of lipophilic pharmaceutically active compounds in the downstream rivers of sewage treatment plants

The occurrence, bioaccumulation and risk assessment of lipophilic pharmaceutically active compounds (LPhACs), such as antibiotics (roxithromycin, erythromycin and ketoconazole), anti-inflammatories (ibuprofen and diclofenac), β-blockers (propranolol), antiepileptics (carbamazepine) and steroid hormones (17α-ethinylestradiol), were investigated in the downstream rivers of sewage treatment plants in Nanjing, China. The results indicate that these LPhACs were widely detected in the surface water and fish samples, with the mean concentrations of the total LPhACs (ΣLPhACs) being in the range of 15.4 and 384.5 ng/L and 3.0 and 128.4 ng/g (wet weight), respectively. The bioaccumulation of the ΣLPhACs in wild fish tissues was generally in the order the liver>brain>gill>muscle. Among the target LPhACs, however, an interspecies difference in tissue distribution was evident for erythromycin. The bioaccumulation factors of LPhACs in the liver and brain, the two major targeted storage sites for toxicants, exhibited an obvious negative correlation with the aquatic concentrations (P<0.05). Finally, risk quotients posed by pharmaceuticals were assessed by comprehensive and comparative methods for different aquatic organisms (algae, daphnids and fish). The overall relative order of susceptibility was estimated to be algae>daphnids>fish. However, the results indicate that diclofenac, ibuprofen and 17α-ethinylestradiol each posed chronic risks for high trophic level organisms (fish). In all of the risk assessments, erythromycin was found to be the most harmful for the most sensitive algae group. In this work, however, the total BAF and toxicological interactions of pharmaceuticals were not performed due to the lack of metabolite information and combined toxicity data, which represents a major hindrance to the effective risk assessment of pharmaceuticals.

Occurrence, bioaccumulation, and trophic magnification of pharmaceutically active compounds in Taihu Lake, China.

The occurrence, bioaccumulation, and trophic magnification of pharmaceutically active compounds, (PhACs) including antibiotics (roxithromycin and erythromycin), non-steroidal anti-inflammatory drugs (ibuprofen and diclofenac), a non-selective β-adrenoceptor blocker (propranolol), an antiepileptic drug (carbamazepine), and steroid estrogens (17β-estradiol and 17α-ethynylestradiol), were investigated in Taihu Lake, China. All eight PhACs were widely detected in surface water and sediment samples with maximal concentrations in the range of 8.74-118 ng L(-1) and 0.78-42.5 ng g(-1) dry weight (dw), respectively. The investigated organisms in the natural freshwater food web in Taihu Lake included phytoplankton, zooplankton, zoobenthos, and fish, and the maximal concentrations of target compounds in these biota samples ranged from 0.65 to 132 ng g(-1) dw. Bioaccumulation factors (BAFs) for all target PhACs were lower than 1000 L kg(-1), suggesting their low bioaccumulation potential in aquatic organisms from Taihu Lake. Trophic magnification factors (TMFs) were estimated at 1.11 for roxithromycin, 0.31 for propranolol, and 1.06 for diclofenac, indicating none of these PhACs underwent trophic magnification in this freshwater food web.

Tissue distribution, bioconcentration, metabolism, and effects of erythromycin in crucian carp (Carassius auratus)

In this study, the tissue distribution, bioconcentration, metabolism and biological effects of the macrolide antibiotic erythromycin (ERY) were investigated in fish using crucian carp (Carassius auratus) as a model. Crucian carp were exposed to various concentrations of ERY (4, 20, and 100 μg/L) for 28 days. The UPLC/MS/MS analysis of both water and tissue provided the bioconcentration of ERY and its metabolites in the fish body. The results from tissue samples showed that a maximum tissue concentration occurred in the muscle and that the bioconcentration factor (BCF) of 72.2 was lower than the theoretical BCF of 90.4 calculated from the octanol-water coefficient of ERY. A significant portion of the absorbed ERY was metabolized via demethylation and dehydration and observed in the form of descladinose in fish. In addition, the relevant biomarkers, including acetylcholinesterase in the brain, as well as 7-ethoxyresorufin O-deethylase and superoxide dismutase in the liver, changed significantly during 28 days of exposure (P<0.05). These results clearly indicated that ERY accumulated in fish and that similar metabolites as those observed in mammals were produced, resulting in the biochemical disturbance of biological systems.

Active biomonitoring of complex pollution in Taihu Lake with Carassius auratus

Carassius auratus bred in clean water were selected to conduct active biomonitoring (ABM) exposures in Meiliang and Gong bays in the northern polluted area of Taihu Lake. The biotransformation enzymes 7-ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST), antioxidant enzymes glutathione peroxidase (GP(X)), reduced glutathione (GSH) content and superoxide dismutase (SOD) and lipoperoxidation (as TBARS) in liver were determined as biomarkers during the field exposure period. At the same time, the contents of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and heavy metals in the surface sediments of biomonitoring sites were measured. The total PAH concentrations ranged from 248.8 to 375.9microgkg(-1) dry weight, PCB from 1.26 to 2.41microgkg(-1), OCP from 0.15 to 2.06microgkg(-1), and heavy metal from 126.3 to 210.0mgkg(-1). The results indicate that complex pollution by persistent organic pollutants and heavy metals is present in the northern end of Taihu Lake and the in situ exposed organisms were stressed. Moreover, Meilaing Bay is a more stressful place to fish living there. The integrated biomarker response (IBR) was calculated by combining different biomarkers to single value, which can be used to describe the toxically-induced stress level of populations in different areas. Pollutant concentrations were displayed as star plots and compared to IBR star plots. There was a visual correlation between the PCB gradient and the OCP gradient measured in the sediments and the IBR variation.

Potential environmental implications of emerging organic contaminants in Taihu Lake, China: Comparison of two ecotoxicological assessment approaches

In this study, the hazard quotient (HQ) and a novel enhanced integrated biomarker response (EIBR) were applied to indirectly/directly estimate the ecotoxicological risk of emerging organic contaminants in Taihu Lake. Nine out of sixteen target compounds were detected in most sampling points at comparable concentrations (1.58-206.95 ng/L). Simultaneously, changes in multi-biomarkers were measured in caged fish for 28 days. The 0HQ results preliminarily indicated that most water areas were at significant risk for adverse effects to aquatic organisms (HQ>10). The prioritisation was then ranked and 17α-ethinylestradiol, diethylstilbestrol and 17β-estradiol were regarded as the greatest hazards. The EIBR, covering multi-biomarkers and their weighting, was applied to field study, and Zhushan Bay was suggested as the most stressful place, followed by Meiliang Bay. The HQ showed significant positive linear correlation with the EIBR (r=0.848, P<0.001), suggesting mutual consistency between the two approaches based on laboratory and field study in ecotoxicological risk assessment.

Biological fate and effects of propranolol in an experimental aquatic food chain

The aim of this study was to evaluate the trophic transfer of the β-blocker propranolol (PRP) in an experimental aquatic food chain involving the green algae Scenedesmus obliquus, the water flea Daphnia magna and the crucian carp Carassius auratus, as well as the metabolism and effects of PRP in the liver of crucian carp. After a 48 h PRP aqueous exposure for algae, with a subsequent 48 h dietary exposure for daphnia and an 8d dietary exposure for crucian carp, PRP was observed in each trophic level, despite significant bioaccumulation did not occur in daphnia and crucian carp. A portion of the absorbed PRP was metabolized by the crucian carp to N-desisopropylated propranolol, propranolol glucuronic acid, monohydroxylated propranolol, hydroxypropranolol glucuronide and dihydroxypropranolol glucuronide, which were similar to those in mammals. In addition, multiple biomarkers in the liver of crucian carp (7-ethoxyresorufin O-deethylase, EROD; 7-benzyloxyresorufin O-dealkylation, BROD; superoxide dismutase, SOD and malondialdehyde, MDA) were measured. BROD and MDA were not significantly affected by PRP, while EROD and SOD did change significantly during the 8d dietary exposure. This work indicated that the trophic transfer of PRP, resulting in biochemical perturbations of fish biological systems, should be a concern for the assessment of the environmental risks to aquatic food chains.

Behavioral and biochemical responses in freshwater fish Carassius auratus exposed to sertraline

Sertraline is one of the most commonly prescribed selective serotonin reuptake inhibitors and is frequently detected in the aquatic environment. However, knowledge regarding relationships among molecular or biochemical endpoints involved in modes of action (MOAs) of sertraline and ecologically important behavioral responses of fish is insufficient. The present study aimed to investigate the bioconcentration and possible adverse outcomes pathways (AOPs) in crucian carp (Carassius auratus) exposed to various concentrations of sertraline (4.36, 21.3 and 116 μg L(-1)) for 7 d. Bioconcentration factor values were in the range of 19.5-626 in liver, 6.94-285 in brain, 4.01-146 in gill and 0.625-43.1 in muscle during the entire period of exposure. Liver superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities and brain acetylcholinesterase (AChE) activity were selected as biochemical endpoints associated with MOAs. Swimming activity, shoaling, feeding rate and food consumption were determined to assess behavioral responses. Fish plasma levels of sertraline exceeding human therapeutic doses were also predicted from external exposure concentrations. Significant enhancements in CAT, GPx, AChE and swimming activities and decreases in shoaling tendency, feeding rate and food consumption were observed when fish plasma levels exceeded human therapeutic thresholds. Shoaling, feeding rate and food consumption were correlated with the activities of SOD, CAT and GST. A significant positive correlation between swimming activity and AChE activity was also observed. As such, our study provides important AOPs linking biochemical responses with ultimate ecologically relevant behavioral endpoints.

Bioconcentration, metabolism and effects of diphenhydramine on behavioral and biochemical markers in crucian carp (Carassius auratus).

Diphenhydramine (DPH), an antihistamine used to alleviate human allergies, is widespread in aquatic environments. However, little is known about the biochemical and behavioral effects of DPH on non-target aquatic animals. In the present study, the tissue distribution, bioconcentration, metabolism, biochemical and behavioral effects were investigated in crucian carp (Carassius auratus) exposed to various concentrations of DPH (0.84, 4.23, 21.7 and 112 μg L(-1)) for 7d. DPH can accumulate in crucian carp, and high concentrations have been observed in the liver and brain with maximum bioconcentration factors of 148 and 81.6, respectively. A portion of the absorbed DPH was metabolized by the crucian carp to N-demethyl DPH and N,N-didemethyl DPH via N-demethylation. Direct fluorimetric assay was employed to assess metabolic activity, while oxidative stress and neurotransmission biomarkers were determined by Diagnostic Reagent Kits. DPH was found to increase hepatic 7-ethoxyresorufin O-deethylase activity in crucian carp with maximal induction of 119%. Concerning the oxidative stress status, DPH significantly inhibited superoxide dismutase (SOD, 37-58%) and glutathione S-transferase (GST, 43-65%) activities and led to a significant increase in malondialdehyde (MDA, 67-140%) levels and catalase (CAT, 38-143%) and glutathione peroxidase (GPx, 39-189%) activities in fish liver. Brain acetylcholinesterase activity was also induced in DPH-exposed crucian carp with maximal induction of 174%. In addition, shoaling was significantly enhanced, while swimming activity and feeding rates were markedly suppressed at DPH concentrations equal to or higher than 21.7 μg L(-1). Furthermore, significant correlations were found between oxidative stress biomarkers (SOD, CAT, GPx, GST and MDA) and behavioral parameters. Collectively, our results confirmed that DPH can accumulate and be metabolized in fish and exert a negative effect at different levels of biological organization.

Interactive effects of selected pharmaceutical mixtures on bioaccumulation and biochemical status in crucian carp (Carassius auratus)

The aim of this study was to evaluate the interactive effects of fluoxetine (FLU), roxithromycin (ROX) and propranolol (PRP) on the bioaccumulation and biochemical responses in the crucian carp Carassius auratus. After 7 days of binary exposure (ROX + FLU and PRP + FLU), the addition of waterborne FLU at nominal concentrations of 4, 20 and 100 μg L(-1) significantly increased the accumulation of ROX and PRP in fish livers in most cases, although elevated ROX and PRP bioaccumulation levels were not observed in muscles or gills. The inductive response of 7-ethoxyresorufin O-deethylase (EROD) to PRP and that of 7-benzyloxy-4-trifluoromethyl-coumarin O-dibenzyloxylase (BFCOD) to ROX were inhibited by the co-administration of FLU at all tested concentrations. Correspondingly, marked inhibition of CYP1A and CYP3A mRNA expression levels was observed in the livers of fish co-treated with FLU + PRP and FLU + ROX relative to their PRP- and ROX-only counterparts, respectively. In addition, as reflected by superoxide dismutase (SOD) activity and malondialdehyde (MDA) content, co-exposure to ROX + FLU and PRP + FLU seemed to induce stronger antioxidant responses than single pharmaceutical exposure in fish livers. This work indicated that the interactive effects of pharmaceutical mixtures could lead to perturbations in the bioaccumulation and biochemical responses in fish.

Recent applications of metal–organic frameworks in sample pretreatment

Metal-organic frameworks are promising materials in diverse analytical applications especially in sample pretreatment by virtue of their diverse structure topology, tunable pore size, permanent nanoscale porosity, high surface area, and good thermostability. According to hydrostability, metal-organic frameworks are divided into moisture-sensitive and water-stable types. In the actual applications, both kinds of metal-organic frameworks are usually engineered into hybrid composites containing magnetite, silicon dioxide, graphene, or directly carbonized to metal-organic frameworks derived carbon. These metal-organic frameworks based materials show good extraction performance to environmental pollutants. This review provides a critical overview of the applications of metal-organic frameworks and their composites in sample pretreatment modes, that is, solid-phase extraction, magnetic solid-phase extraction, micro-solid-phase extraction, solid-phase microextraction, and stir bar solid extraction.