Next Article in Journal
Comparative Analysis of Skeletal Muscle Metabolites of Fish with Various Rates of Aging
Previous Article in Journal
Social Behavior and Welfare in Nile Tilapia
Communication

Preliminary Monitoring of Praziquantel in Water and Sediments at a Japanese Amberjack (Seriola quinqueradiata) Aquaculture Site

1
Graduate School of Agriculture, Ehime University 3-5-7, Tarumi, Matsuyama, Ehime 790-8566, Japan
2
Owase-bussan Co. Ltd., 1-33 Hayashi-machi, Owase, Mie 519-3612, Japan
*
Author to whom correspondence should be addressed.
Fishes 2019, 4(2), 24; https://doi.org/10.3390/fishes4020024
Received: 22 February 2019 / Revised: 26 March 2019 / Accepted: 27 March 2019 / Published: 28 March 2019

Abstract

Praziquantel (PZQ), an active compound against Platyhelminthes, is an essential anthelmintic for the aquaculture industry. However, there are few reports of the environmental risks of PZQ use in aquaculture. In this study, we monitored PZQ in water and sediment at an aquaculture site of Japanese amberjack, also called yellowtail (Seriola quinqueradiata). Although PZQ was detected in water during treatment and 3 days post-treatment, PZQ levels were below the detectable limit in water 60 m from the net pen during the treatment, and in all sediment samples. In this preliminary study, we could not detect residue of PZQ from sediments in the aquaculture site, and no evidence about environmental effect of PZQ administration was obtained.
Keywords: Praziquantel; Japanese amberjack (Seriola quinqueradiata); water; sediment Praziquantel; Japanese amberjack (Seriola quinqueradiata); water; sediment

1. Introduction

Praziquantel (PZQ), 2-(cyclohexyl-carbonyl)-1,2,3,6,7,11b-hexahydro-4H-pyrazino [2,1-a] isoquinoline-4-one, is an effective substance against many species of Platyhelminthes [1,2]. PZQ has been used for both human and veterinary medicine. Compared with benzimidazole-based compounds, mebendazole and febantel, PZQ is the most widely used in the treatment of various fish parasites [3]. Although PZQ surface-coating can affect palatability of feed pellet for yellowtail kingfish (Seriola lalandi) [4,5], in-feed administration of PZQ is the only reliable method to control the internal parasites, such as blood flukes caused by trematodes [3,6].
PZQ is an essential anthelmintic for the aquaculture industry. In Japan, PZQ was approved for oral administration in cultured fish belonging to the order Perciformes against Benedenia seriolae or Cardicola opisthorchis parasites. Heavy use of drugs, including antibiotics, in aquaculture results in environmental burdens, for example, alterations in water column and sediment microflora, and emergence of drug resistance [7]. However, few reports have addressed the environmental impacts of veterinary use of PZQ [8]. Therefore, we preliminarily monitored water and sediment PZQ levels after oral administration in an aquaculture site cultivating Japanese amberjack, also called yellowtail (Seriola quinqueradiata).

2. Results

Water PZQ levels pre-treatment, during the treatment, and post-treatment are shown in Table 1. Although 0.003 mg/L of PZQ was detected in net pen surface water during treatment, 30 m or 60 m distance from the pen was sufficient for PZQ to disperse. Further, PZQ was below the detectable limit (0.01 mg/kg dry weight) in all sediment samples, including the sample collected directly beneath the net pen (Table 2).

3. Discussion

Drug use in aquaculture, including PZQ, should be minimized to mitigate environmental risks as well as food safety concerns. This preliminary study indicates that the dosage and administration protocol utilized did not result in PZQ accumulation in the aquaculture site, even though PZQ was used for 10 years at least. The finding that PZQ was nearly undetectable in water 3 days post-treatment is consistent with a prior study, which demonstrated that 2 mg/L PZQ was degraded to below the detectable limit in a recirculating system within 2–3 days [9].
The environmental impact of orally administered emamectin benzonate (EB), an anti-sea lice active compound, has been studied. EB was detected in sediment samples taken 1–4 months post-treatment at an Atlantic salmon (Salmo salar) farm in Scotland [10] and in sediment samples collected during treatment and 116 days post-treatment at a salmon farm in Canada [11]. Contrastingly, PZQ was not detected from sediment samples collected 1 month post-treatment in this study.
However, the duration of EB efficacy was reported to be 3–4 months [12,13], while PZQ is rapidly absorbed and eliminated in 24 h after an oral administration in yellowtail kingfish (Seriola lalandi) [14,15] and in Pacific bluefin tuna (Thunnus orientalis) [16]. In Japanese amberjack, concentrations of PZQ in plasma, skin mucus, muscle liver, and kidney decrease to below detectable limits within 48 h of oral administration of 150 mg/kg for 3 days [17]. Small amounts of PZQ were detected from the water 3 days post-treatment, but the possibility of re-detection from water after that sampling point was thought to be low. Although environmental effects of PZQ metabolites should also be considered, the anthelmintic activity of PZQ metabolites in yellowtail kingfish was reported to be minor [18]. In the current preliminary study, no evidence regarding environmental impacts of oral PZQ administration in Japanese amberjack aquaculture was obtained, although further monitoring will be needed.
Because parasitic diseases caused by Monogenea and Trematoda have become a serious problem for Japanese amberjack aquaculture [19], oral treatment with PZQ is essential to control these diseases. Recently, PZQ-resistance in Schistosoma mansoni and Schistosoma japonicum was reported to be experimentally induced under continuous drug pressure [20]. Although PZQ drug resistance in parasites infecting cultured fish has not been previously reported, careful monitoring should be undertaken in order to check for sensitivity to PZQ and also mitigate the risk of potential infections spreading to wild fish.
In conclusion, we preliminarily monitored water and sediment PZQ levels after oral administration in an aquaculture site cultivating Japanese amberjack. Although PZQ was detected in water collected from the surface water of the net pen during PZQ administration, it rapidly dispersed, and was not detected in the sediment—even in sediment collected directly beneath the net pen.

4. Materials and Methods

4.1. Sample Collection

Samples were taken from an aquaculture site cultivating Japanese amberjack in Owase, Mie, Japan from 22 June to 24 August 2018. A net pen (Length: 9 m, Width: 9 m, Depth: 10.5 m) located at 34°04′38.8″ N/136°13′12.4″ E was monitored for PZQ levels (Figure 1). Latitude/longitude and water depth in the sampling points are indicated in Table 3. Symptoms of trematode whirling disease caused by Galactosomum sp. were detected in juvenile Japanese amberjacks in the monitored net pen, and Hada Clean® (Bayer Japan, Osaka, Japan) which includes 50% of PZQ as an active agent, was administered orally for 3 days from 25 July to 27 July, 2018, in the monitored net pen under veterinarian prescription (Table 4). The drug was attached to feed pellets using a fish oil coating. The symptoms of trematode whirling disease are observed in the site every year, and oral administration of PZQ to the monitored net pen has been repeated over 10 years at least.
Surface water and sediments were collected 0 m, 30 m, and 60 m from the net pen along the water current, and additionally outside of the aquaculture site (beyond the map in Figure 1, and approximately 800 m south-south-east from the net pen). Water samples were collected using a water bottle sampler (Rigo, Tokyo, Japan) at 1 m depth, and sediment samples were collected using an Ekman-Birge bottom sampler (Rigo, Tokyo, Japan). All samples were protected from UV and stored at 4 °C until analysis.

4.2. PZQ Detection

One hundred-milliliter water samples were extracted using solid phase columns (C18 [WAT020515], Waters, Milford, MA, USA) at 10 mL/minute. The columns were centrifuged to remove the water inside, and filtered water was extracted with methanol. Methanol was removed with a nitrogen gas purge. The samples were prepared for analysis at a constant volume of 1 mL water and 2 mL acetonitrile. 30 mL of acetone was added to 5 g of sediment samples, mixed by shaking, and homogenized with an ultrasonic wave. Samples were then centrifuged, and supernatants were collected. 30 mL of acetone was added to the precipitate, and the same process was repeated to collect the supernatant. The combined supernatants were concentrated with evaporation and nitrogen gas purging. The samples were prepared for analysis at a constant volume of 1 mL water and 2 mL acetonitrile. PZQ was detected with LC (1200 LC, Agilent, Santa Clara, CA, USA) and MS/MS (6410 Triple Quad LC/MS/MS, Agilent, Santa Clara, CA, USA). Limits of detection were 0.0001 mg/L in water, and 0.01 mg/kg dry weight in sediment.

Author Contributions

Conceptualization: A.I.; sample collection: A.I., M.K., and Y.T.; analysis: A.I.; writing: A.I.

Funding

This research was funded by World Wildlife Fund (WWF) and Japan Seriola Initiative (JSI).

Acknowledgments

We acknowledge Satoshi Maekawa (WWF Japan) for providing technical advice, and IDEA Consultants, Inc for assistance with detection. We also thank the Seriola farmers belonging to JSI.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Doenhoff, M.J.; Cioli, D.; Utzinger, J. Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis. Curr. Opin. Infect. Dis. 2008, 21, 659–667. [Google Scholar] [CrossRef]
  2. Chai, J. Praziquantel Treatment in Trematode and Cestode Infections: An Update. Infect. Chemother. 2013, 45, 32. [Google Scholar] [CrossRef] [PubMed]
  3. Ogawa, K. Diseases of cultured marine fishes caused by Platyhelminthes (Monogenea, Digenea, Cestoda). Parasitology 2015, 142, 178–195. [Google Scholar] [CrossRef] [PubMed]
  4. Williams, R.E.; Ernst, I.; Chambers, C.B.; Whittington, I.D. Efficacy of orally administered praziquantel against Zeuxapta seriolae and Benedenia seriolae (Monogenea) in yellowtail kingfish Seriola lalandi. Dis. Aquat. Organ. 2007, 77, 199–205. [Google Scholar] [CrossRef] [PubMed]
  5. Partridge, G.J.; Burge, T.; Lymbery, A.J. A comparison of the palatability of racemic praziquantel and its two enantioseparated isomers in yellowtail kingfish Seriola lalandi (Valenciennes, 1833). Aquac. Res. 2017, 48, 1735–1743. [Google Scholar] [CrossRef]
  6. Bader, C.; Starling, D.E.; Jones, D.E.; Brewer, M.T. Use of praziquantel to control platyhelminth parasites of fish. J. Vet. Pharmacol. Ther. 2019, 49, 139–153. [Google Scholar] [CrossRef] [PubMed]
  7. Cabello, F.C. Heavy use of prophylactic antibiotics in aquaculture: A growing problem for human and animal health and for the environment. Environ. Microbiol. 2006, 8, 1137–1144. [Google Scholar] [CrossRef] [PubMed]
  8. Bártíková, H.; Podlipná, R.; Skálová, L. Veterinary drugs in the environment and their toxicity to plants. Chemosphere 2016, 144, 2290–2301. [Google Scholar] [CrossRef] [PubMed]
  9. Thomas, A.; Dawson, M.R.; Ellis, H.; Stamper, M.A. Praziquantel degradation in marine aquarium water. PeerJ 2016, 4, e1857. [Google Scholar] [CrossRef] [PubMed]
  10. Telfer, T.C.; Baird, D.J.; McHenery, J.G.; Stone, J.; Sutherland, I.; Wislocki, P. Environmental effects of the anti-sea lice (Copepoda: Caligidae) therapeutant emamectin benzoate under commercial use conditions in the marine environment. Aquaculture 2006, 260, 163–180. [Google Scholar] [CrossRef]
  11. DFO. Assessment of the Fate of Emamectin Benzoate, the Active Ingredient in SLICE®, near Aquaculture Facilities in British Columbia and its Effect on Spot Prawns (Pandalus platyceros). Canadian Science Advisory Secretariat Science Advisory Report 2011/082. Available online: http://www.dfo-mpo.gc.ca/Library/346389.pdf (accessed on 22 February 2019).
  12. Stone, J.; Sutherland, I.H.; Sommerville, C.; Richards, R.H.; Endris, R.G. The duration of efficacy following oral treatment with emamectin benzoate against infestations of sea lice, Lepeophtheirus salmonis (Kroyer), in Atlantic salmon Salmo salar L. J. Fish Dis. 2000, 23, 185–192. [Google Scholar] [CrossRef]
  13. Gustafson, L.; Ellis, S.; Robinson, T.; Marenghi, F.; Endris, R. Efficacy of emamectin benzoate against sea lice infestations of Atlantic salmon, Salmo salar L.: evaluation in the absence of an untreated contemporary control. J. Fish Dis. 2006, 29, 621–627. [Google Scholar] [CrossRef] [PubMed]
  14. Tubbs, L.; Tingle, M. Bioavailability and pharmacokinetics of a praziquantel bolus in kingfish Seriola lalandi. Dis. Aquat. Organ. 2006, 69, 233–238. [Google Scholar] [CrossRef] [PubMed]
  15. Tubbs, L.A.; Tingle, M.D. Effect of dose escalation on multiple dose pharmacokinetics of orally administered praziquantel in kingfish Seriola lalandi. Aquaculture 2006, 261, 1168–1174. [Google Scholar] [CrossRef]
  16. Ishimaru, K.; Mine, R.; Shirakashi, S.; Kaneko, E.; Kubono, K.; Okada, T.; Sawada, Y.; Ogawa, K. Praziquantel treatment against Cardicola blood flukes: Determination of the minimal effective dose and pharmacokinetics in juvenile Pacific bluefin tuna. Aquaculture 2013, 402–403, 24–27. [Google Scholar] [CrossRef]
  17. Food Safety Commission of Japan. Risk Assessment Report on an Oral Administering Agent for Veterinary Use into Hoses, Containing Ivermectin and Praziquantel as Active Ingredients. Available online: http://www.fsc.go.jp/fsciis/evaluationDocument/show/kya20071024027 (accessed on 22 February 2019).
  18. Tubbs, L.; Mathieson, T.; Tingle, M. Metabolism of praziquantel in kingfish Seriola lalandi. Dis. Aquat. Org. 2008, 78, 225–233. [Google Scholar] [CrossRef]
  19. Ogawa, K.; Yokoyama, H. Parasitic Diseases of Cultured Marine Fish in Japan. Fish Pathol. 1998, 33, 303–309. [Google Scholar] [CrossRef]
  20. Wang, W.; Wang, L.; Liang, Y.-S. Susceptibility or resistance of praziquantel in human schistosomiasis: A review. Parasitol. Res. 2012, 111, 1871–1877. [Google Scholar] [CrossRef] [PubMed]
Figure 1. Sampling Locations. The circle indicates the monitored net pen. Samples were collected 0 m, 30 m, and 60 m (arrowheads) from the net pen along the water current. The dominant current direction in this site is indicated by an arrow. This map is based on an aerial photograph published by the Geospatial Information Authority of Japan. Scale bar: 50 m.
Figure 1. Sampling Locations. The circle indicates the monitored net pen. Samples were collected 0 m, 30 m, and 60 m (arrowheads) from the net pen along the water current. The dominant current direction in this site is indicated by an arrow. This map is based on an aerial photograph published by the Geospatial Information Authority of Japan. Scale bar: 50 m.
Fishes 04 00024 g001
Table 1. Detection of praziquantel (PZQ) in water.
Table 1. Detection of praziquantel (PZQ) in water.
StatusSampling DateDistance from PennPZQ (mg/L)
Pre-treatment22 June 20180 m3<0.0001
During the treatment26 July 20180 m30.00343 ± 0.00021
30 m30.00013 ± 0.00006
60 m2<0.0001
3 days post-treatment30 July 20180 m30.00008 ± 0.00003
30 m3<0.0001
60 m3<0.0001
Limit of detection (LOD) = 0.0001 mg/L. Concentrations of PZQ were represented by means ± SD calculated as lower than LOD (<0.0001) replaced with LOD/2.
Table 2. Detection of PZQ in sediment.
Table 2. Detection of PZQ in sediment.
StatusSampling DateDistance from PennPZQ (mg/kg Dry Weight)
Pre-treatment22 June 20180 m3<0.01
30 m3<0.01
60 m3<0.01
Outside1<0.01
1 week post-treatment3 August 20180 m3<0.01
30 m3<0.01
60 m3<0.01
4 weeks post-treatment24 August 20180 m3<0.01
30 m3<0.01
60 m3<0.01
Limit of detection = 0.01 mg/kg dry weight.
Table 3. Information about sampling points.
Table 3. Information about sampling points.
Sampling PointLatitude/LongitudeWater Depth
0 m34°04′38.8″ N/136°13′12.4″ E29.1 m
30 m34°04′38.46″ N/136°13′11.03″ E29.4 m
60 m34°04′38.41″ N/136°13′10.01″ E29.6 m
Outside of the site34°04′16.70″ N/136°13′28.62″ E34.5 m
Table 4. Oral administration of PZQ in the monitored net pen.
Table 4. Oral administration of PZQ in the monitored net pen.
Number of FishBody WeightBiomassOral Administration of PZQ
9811200 g/fish1962.2 kg50 mg/kg/day
Back to TopTop