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Effect of excessive doses of oxytetracycline on stress-related biomarker expression in coho salmon

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Abstract

Fish are exposed to a wide variety of environmental stressors, such as chemicals and acute changes in temperature. Oxytetracycline (OTC) has been used as an antibiotic for many kinds of bacterial diseases in cultured fish, but excessive doses of OTC are known to cause side effects in fish and can have negative effects on their environment. In the present study, we examined stress-related biomarker expression in response to excessive doses of dietary OTC in coho salmon (Oncorhynchus kisutch). Fish received OTC (100 mg/kg body weight/day) orally for 2 weeks. The percentage of liver to body weight (hepatosomatic index; HSI) and plasma biochemical parameter, alanine aminotransferase (ALT) activity, of the group fed a diet containing OTC were observed to be significantly higher than those of the control group. The total glutathione (tGSH) levels in the liver of OTC-fed fish were four fold higher than those in control fish and double the control levels in muscle and stomach. Plasma tGSH levels in OTC-fed fish were also higher than those in control fish. Expression levels of heat shock protein 70 in the liver, muscle, and stomach decreased by OTC administration. Accordingly, OTC-induced stress might increase the metabolic turnover of GSH due to consumption by scavenging oxidants generated by stress. These results concerning the changing patterns of stress-related biomarkers indicate that excessive doses of OTC fed to coho salmon induce oxidative stress, which might enhance oxidation in the body and result in damage to tissues, especially in the liver. The present results also suggest that tissue-specific damage caused by OTC might already exist in fish.

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References

  • Adams SM (2005) Assessing cause and effect of multiple stressors on marine systems. Mar Pollut Bull 51:649–657

    Article  CAS  Google Scholar 

  • Allen RG, Tresini M (2000) Oxidative stress and gene regulation. Free Radic Biol Med 28:463–499

    Article  CAS  Google Scholar 

  • Ameur WB, De Lapuente J, Megdiche YE, Barhoumi B, Trabelsi S, Camps L, Serret J, Ramos-Lopez D, Gonzalez-Linares J, Driss MR, Borras M (2012) Oxidative stress, genotoxicity and histopathology biomarker responses in mullet (Mugil cephalus) and sea bass (Dicentrarchus labrax) liver from Bizerte Lagoon (Tunisia). Mar Pollut Bull 64:241–251

    Article  Google Scholar 

  • Arrigo A-P (1999) Gene expression and the thiol redox state. Free Radic Biol Med 27:936–944

    Article  CAS  Google Scholar 

  • Barton BA, Iwama GK (1991) Physiological change in fish from stress in aquaculture with emphasis on the response and effects of corticosteroids. Annu Rev Fish Dis 1:3–26

    Article  Google Scholar 

  • Basu N, Nakano T, Grau EG, Iwama GK (2001) The effects of cortisol on heat shock protein 70 levels in two fish species. Gen Comp Endocrinol 124:97–105

    Article  CAS  Google Scholar 

  • Basu N, Todgham AE, Ackerman PA, Bibeau MR, Nakano K, Shulte PM, Iwama GK (2002) Heat shock protein genes and their functional significance in fish. Gene 295:173–183

    Article  CAS  Google Scholar 

  • Bruno DW (1989) An investigation into oxytetracycline residues in Atlantic salmon, Salmo salar L. J Fish Dis 12:77–86

    Article  Google Scholar 

  • Bureau of Food Safety and Consumer Affairs, Ministry of Agriculture, Forestry and Fisheries of Japan (2015): the guideline for usage of drugs for fisheries. Tokyo, pp. 8–12

  • Burridge L, Weis JS, Cabello F, Pizarro J, Bostick K (2010) Chemical use in aquaculture: a review of current practices and possible environmental effects. Aquaculture 306:7–23

    Article  CAS  Google Scholar 

  • Donaldson EM, Fagerlund UHM, Higgs DA, McBride JR (1979) Hormonal enhancement of growth. In: Hoar WS, Randall DJ, Brett JR (eds) Bioenergetics and growth. Fish physiology 8. Academic, New York, pp 455–597

    Chapter  Google Scholar 

  • Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95

    Article  CAS  Google Scholar 

  • Elia AC, Ciccotelli V, Pacini N, Dorr AJM, Gili M, Natali M, Gasco L, Prearo M, Abete MC (2014) Transferability of oxytetracycline (OTC) from feed to carp muscle and evaluation of the antibiotic effects on antioxidant systems in liver and kidney. Fish Physiol Biochem 40:1055–1068

    CAS  Google Scholar 

  • Feder ME, Hofmann GE (1999) Heat-shock proteins, molecular chaperones, and the stress response. Annu Rev Physiol 61:243–282

    Article  CAS  Google Scholar 

  • Forbes VE, Palmqvist A, Bach L (2006) The use and misuse of biomarkers in ecotoxicology. Environ Toxicol Chem 25:272–280

    Article  CAS  Google Scholar 

  • Griffiths HR, Dias IHK, Willetts RS, Devitt A (2014) Redox regulation of protein damage in plasma. Redox Biol 2:430–435

    Article  CAS  Google Scholar 

  • Guardiola FA, Cerezuela R, Meseguer J, Esteban MA (2012) Modulation of immune parameters and expression if genes of gilthead seabream (Sparus aurata L.) by dietary administration of oxytetracycline. Aquaculture 334–337:51–57

    Article  Google Scholar 

  • Hagger JA, Jones MB, Lowe D, Leonard DRP, Owen R, Galloway TS (2008) Application of biomarkers for improving risk assessments of chemicals under the Water Framework Directive: a case study. Mar Pollut Bull 56:1111–1118

    Article  CAS  Google Scholar 

  • He X, Nie X, Yang Y, Liu X, Pan D, Cheng Z, Liang X (2012) Multi-biomarker responses in fishes from two typical marine aquaculture regions of South China. Mar Pollut Bull 64:2317–2324

    Article  CAS  Google Scholar 

  • Ho E, Galougahi KK, Liu C-C, Bhindi R, Figtree GA (2013) Biological markers of oxidative stress: applications to cardiovascular research and practice. Redox Biol 1:483–491

    Article  CAS  Google Scholar 

  • Hori TSF, Avilez IM, Iwama GK, Johnson SC, Moraes G, Afonso LOB (2008) Impairment of the stress response in matrinxa juveniles (Brycon amazonicus) exposed to low concentrations of phenol. Comp Biochem Physiol 147C:416–423

    CAS  Google Scholar 

  • Ikeda Y, Ozaki H, Sezaki K (1986) Chemical composition of plasma, blood atlas of fishes. Midori Shobo, Tokyo, pp 304–323

    Google Scholar 

  • Iwama GK, Thomas PT, Forsyth RB, Vijayan MM (1998) Heat shock protein expression in fish. Rev Fish Biol Fish 8:35–56

    Article  Google Scholar 

  • Iwama GK, Afonso LOB, Todgham AE, Ackerman PA, Nakano K (2004) Are hsps suitable for indicating stressed states in fish? J Exp Biol 207:15–19

    Article  CAS  Google Scholar 

  • Iwama GK, Afonso LOB, Vijayan MM (2006) Stress in fishes. In: Evans DH, Claiborne JB (eds) The physiology of fishes (3rd Ed.). CRC Press, Boca Raton, pp 319–342

    Google Scholar 

  • Ji LL (1995) Oxidative stress during exercise: implication of antioxidant nutrients. Free Radic Biol Med 18:1079–1086

    Article  CAS  Google Scholar 

  • Kameda M, Nakano T, Yamaguchi T, Sato M, Afonso LOB, Iwama GK, Devlin RH (2008) Effects of heat shock on growth hormone receptor expression in coho salmon. Proc 5th World Fish Cong, Yokohama, Oct. 20–25, 3f-16

  • Lushchak VI (2011) Environmentally induced oxidative stress in aquatic animals. Aquat Toxicol 101:13–30

    Article  CAS  Google Scholar 

  • Malvisi J, Della Rocca G, Anfossi P, Giorgetti G (1996) Tissue distribution and residue depletion of oxytetracycline in sea bream (Sparus aurata) and sea bass (Dicentrarchus labrax) after oral administration. Aquaculture 147:159–168

    Article  CAS  Google Scholar 

  • Mcdonald DG, Milligan CL (1992) Chemical properties of the blood. In: Hoar WS, Randall DJ, Farrell AP (eds) The cardiovascular system. Fish physiology 12B. Academic, New York, pp 55–133

    Chapter  Google Scholar 

  • Moreland JJ, Arrieta DE, Washburn BS (2000) Effects of estrogen on the stress response in CuSO4-exposed PLHC-1 cells. Mar Environ Res 50:509–512

    Article  CAS  Google Scholar 

  • Moriyama S, Ayson FG, Kawauchi H (2000) Growth regulation by insulin-like growth factor-I in fish. Biosci Biotech Biochem 64:1553–1562

    Article  CAS  Google Scholar 

  • Mujahid A, Yoshiki Y, Akiba Y, Toyomizu M (2005) Superoxide radical production in chicken skeletal muscle induced by acute heat stress. Poult Sci 84:307–314

    Article  CAS  Google Scholar 

  • Nakano T (2007) Microorganisms. In: Nakagawa H, Sato M, Gatlin DM III (eds) Dietary supplements for the health and quality of cultured fish. CAB International, Oxfordshire, pp 86–108

    Chapter  Google Scholar 

  • Nakano T (2011) Stress in fish. Yoshoku (Aquaculture Magazine) 48:64–67

    CAS  Google Scholar 

  • Nakano T (2015) Rising to the challenge of reconstructing the coastal fisheries environment following the massive tsunami in Japan: the national 10-year “Tohoku Ecosystem-Associated Marine Sciences (TEAMS)”. In: Ceccaldi HJ, Hénocque Y, Koike Y, Komatsu T, Stora G, Tusseau-Vuillemin M-H (eds) Marine productivity: perturbations and resilience of socio-ecosystems. Springer International Publishing AG, Cham, Switzerland, pp 63–68

    Google Scholar 

  • Nakano T, Takeuchi M (1997) Relationship between fish and reactive oxygen species. Yoshoku (Aquaculture Magazine) 34:69–73

    Google Scholar 

  • Nakano T, Sato M, Takeuchi M (1992a) Partial purification and properties of glutathione peroxidase from carp hepatopancreas. Comp Biochem Physiol 102B:31–35

    CAS  Google Scholar 

  • Nakano T, Sato M, Takeuchi M (1992b) Glutathione peroxidase of fish. J Food Sci 57:1116–1119

    Article  CAS  Google Scholar 

  • Nakano T, Tosa M, Takeuchi M (1995) Improvement of biochemical features in fish health by red yeast and synthetic astaxanthin. J Agric Food Chem 43:1570–1573

    Article  CAS  Google Scholar 

  • Nakano T, Kanmuri T, Sato M, Takeuchi M (1999a) Effect of astaxanthin rich red yeast (Phaffia rhodozyma) on oxidative stress in rainbow trout. Biochim Biophys Acta 1426:119–125

    Article  CAS  Google Scholar 

  • Nakano T, Miura Y, Wazawa M, Sato M, Takeuchi M (1999b) Red yeast Phaffia rhodozyma reduces susceptibility of liver homogenate to lipid peroxidation in rainbow trout. Fish Sci 65:961–962

    Article  CAS  Google Scholar 

  • Nakano T, Wazawa M, Yamaguchi T, Sato M, Iwama GK (2004) Positive biological actions of astaxanthin in rainbow trout. Mar Biotechnol 6:S100–S105

    Google Scholar 

  • Nakano T, Masuda M, Suzuki T, Ohshima H (2012a) Inhibition by polyphenolic phytochemicals and sulfurous compounds of the formation of 8-chloroguanosine mediated by hypochlorous acid, human myeloperoxidase, and activated human neutrophils. Biosci Biotechnol Biochem 76:2208–2213

    Article  CAS  Google Scholar 

  • Nakano T, Shiba Y, Yamaguchi T, Sato M, Ohshima H (2012b) Natural marine products inhibit formation of 8-chloroguanosine mediated by hypochlorous acid, myeloperoxidase and activated neutrophils. Free Radic Biol Med 53:S95

  • Nakano T, Afonso LO, Beckman BR, Iwama GK, Devlin RH (2013) Acute physiological stress down-regulates mRNA expressions of growth-related genes in coho salmon. PLoS ONE 8:e71421

    Article  Google Scholar 

  • Nakano T, Kameda M, Shoji Y, Hayashi S, Yamaguchi T, Sato M (2014) Effect of severe environmental thermal stress on redox state in salmon. Redox Biol 2:772–776

    Article  CAS  Google Scholar 

  • Nakano T, Kameda M, Yamaguchi T, Sato M, Afonso LOB, Beckman BR, Iwama GK, Devlin RH (2015) Effect of thermal stressors on growth-related gene expressions in cultured fish. In: Ceccaldi HJ, Hénocque Y, Koike Y, Komatsu T, Stora G, Tusseau-Vuillemin M-H (eds) Marine productivity: perturbations and resilience of socio-ecosystems. Springer International Publishing AG, Cham, Switzerland, pp 147–157

    Google Scholar 

  • Namdari R, Abedini S, Law FCP (1996) Tissue distribution and elimination of oxytetracycline in seawater chinook and coho salmon following medicated-feed treatment. Aquaculture 144:27–38

    Article  CAS  Google Scholar 

  • Nemcsok J, Benedeczky I (1995) Pesticide metabolism and the adverse effects of metabolites on fishes. In: Hochachka PW, Mommsen TP (eds) Environmental and ecological biochemistry. Biochemistry and molecular biology of fishes. Elsevier, Amsterdam, pp 313–348

    Chapter  Google Scholar 

  • Neuhaus-Steinmetz U, Xu C, Fracella F, Oberheitmann B, Richter-Landsberg C, Rensing L (1994) Heat shock response and cytotoxicity in C6 rat glioma cells: structure-activity relationship of different alcohols. Moll Pharmacol 45:36–41

    CAS  Google Scholar 

  • Niki E (1988) Ascorbic acid, glutathione. In: Nakano M, Asada K, Oyanagui Y (eds) Reactive oxygen. Kyoritsu Shuppan, Tokyo, pp 321–326

    Google Scholar 

  • Nogawa H, Yagisawa I (1994) Optimum environmental condition for rearing juvenile chum salmon (Oncorhynchus keta): a review. Sci Rep Hokkaido Salm Hatch 48:31–39

    Google Scholar 

  • Ozaki H (1971) Liver weight. Fish physiology. Midori Shobo, Tokyo, pp 97–120

  • Ozaki H (1978) Diagnosis of fish health by blood analysis. In: Ishikawa T, Hanyu I, Hibiya K (eds) Respiration and circulation of fish. Koseisha Koseikaku, Tokyo, pp 63–80

    Google Scholar 

  • Ozaki H (1980) Antibiotics 2. The pharmacology of fishes. Midori Shobo, Tokyo, pp 73–110

    Google Scholar 

  • Pari L, Gnanasoundari M (2006) Influence of naringenin on oxytetracycline mediated oxidative damage in rat liver. Basic Clin Pharmacol Toxicol 98:456–461

    Article  CAS  Google Scholar 

  • Peng J, Jones LG, Watson K (2000) Stress proteins as biomarkers of oxidative stress: effects of antioxidant supplements. Free Radic Biol Med 28:1598–1606

    Article  CAS  Google Scholar 

  • Petrenko I, Titov VI, Vladimirov IA (1995) Generation of active forms of oxygen by antibiotics of the tetracycline series during tetracycline catalysis of oxidation of ferrous ion. Antibiot Khimioter 40:3–8

    CAS  Google Scholar 

  • Pickering AD (1993) Growth and stress in fish production. Aquaculture 111:51–63

    Article  Google Scholar 

  • Prunet P, Overli O, Douxfils J, Bernardini G, Kestemont P, Baron D (2012) Fish welfare and genomics. Fish Physiol Biochem 38:43–60

    Article  CAS  Google Scholar 

  • Quinlan GJ, Gutteridge MC (1988) Hydroxyl radical generation by the tetracycline antibiotics with free radical damage to DNA, lipids and carbohydrate in the presence of iron and copper salts. Free Radic Biol Med 5:341–348

  • Regoli F, Giuliani ME (2014) Oxidative pathways of chemical toxicity and oxidative stress biomarkers in marine organisms. Mar Environ Res 93:106–117

    Article  CAS  Google Scholar 

  • Reineck M (2010) Influences of the environment on the endocrine and paracrine fish growth hormone-insulin-like growth factor-I system. J Fish Biol 76:1233–1254

    Article  Google Scholar 

  • Rogstad A, Hormazabal V, Ellingsen OF, Rasmussen KE (1991) Pharmacokinetic study of oxytetracycline in fish. I. Absorption, distribution and accumulation in rainbow trout in freshwater. Aquaculture 96:219–226

    Article  CAS  Google Scholar 

  • Shin MH, Moon YJ, Seo J-E, Lee Y, Kim KH, Chung JH (2008) Reactive oxygen species produced by NADPH oxidase, xanthine oxidase, and mitochondrial electron transport system mediate heat shock-induced MMP-1 and MMP-9 expression. Free Radic Biol Med 44:635–645

    Article  CAS  Google Scholar 

  • Sies H (1999) Glutathione and its role in cellular functions. Free Radic Biol Med 27:916–921

    Article  CAS  Google Scholar 

  • Srikanth K, Pereira E, Duarte AC, Ahmad I (2013) Glutathione and its dependent enzymes’ modulatory responses to toxic metals and metalloids in fish—a review. Environ Sci Pollut Res 20:2133–2149

    Article  CAS  Google Scholar 

  • Topic Popovic N, Howell T, Babish JG, Bowser PR (2012) Cross-sectional study of hepatic CYP1A and CYP3A enzymes in hybrid striped bass, channel catfish and Nile tilapia following oxytetracycline treatment. Res Vet Sci 92:283–291

    Article  CAS  Google Scholar 

  • Ueno R, Kinoshita A, Wakabayashi J (2004) Comparative pharmacokinetics of oxytetracycline in eel and its fate in a close aquatic environment. Aquaculture 235:53–63

    Article  CAS  Google Scholar 

  • Uno K, Aoki T, Ueno R (1992) Pharmacokinetic study of oxytetracycline in cultured rainbow trout, amago salmon and yellowtail. Nippon Suisan Gakk 58:1151–1156

  • Valavanidis A, Vlahogianni T, Dassenakis M, Scoullos M (2006) Molecular biomarkers of oxidative stress in aquatic organisms in relation to toxic environmental pollutants. Ecotoxicol Environ Saf 64:178–189

    Article  CAS  Google Scholar 

  • Vasseur P, Cossu-Leguille C (2003) Biomarkers and community indices as complementary tools for environmental safety. Environ Int 28:711–717

    Article  CAS  Google Scholar 

  • Yamamoto Y (1981) Determination of toxicity by biochemical method. In: Egami N (ed) Fish as laboratory animals. Soft Science, Tokyo, pp 420–448

    Google Scholar 

  • Yonar ME (2012) The effect of lycopene on oxytetracycline-induced oxidative stress and immunosuppression in rainbow trout (Oncorhynchus mykiss, W.). Fish Shellfish Immunol 32:994–1001

    Article  CAS  Google Scholar 

  • Yonar ME, Yonar SM, Silici S (2011) Protective effect of propolis against oxidative stress and immunosuppression induced by oxytetracycline in rainbow trout (Oncorhynchus mykiss, W.). Fish Shellfish Immunol 31:318–325

    Article  Google Scholar 

  • Zhang Q, Li X (2007) Pharmacokinetics and residue elimination of oxytetracycline in grass carp, Ctenopharyngodon idellus. Aquaculture 272:140–145

    Article  CAS  Google Scholar 

  • Zounkova R, Klimesova Z, Nepejchalove L, Hilscherova K, Blaha L (2011) Complex evaluation of ecotoxicity and genotoxicity of antimicrobials oxytetracycline and flumequine used in aquaculture. Environ Toxicol Chem 30:1184–1189

    Article  CAS  Google Scholar 

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Acknowledgments

The authors wish to thank Mr. T. Mandeville at New Day English Language Services, Sendai, Japan, for editing this manuscript. The authors are grateful to Drs. M. Sato, T. Yamaguchi, and H. Shirakawa at Tohoku University, Japan; S. Lertsiri at Mahidol University; and U. Na-Nakorn and W. Worawattanamateekul at Kasetsart University, Thailand, for valuable discussion and suggestions. The authors wish to thank Miss. A. Yamauchi and Miss. R. Okada at Tohoku University for assistance in laboratory work. The authors also acknowledge Drs. T. Nakano at Osaka University and K. Kubono at ASKA Animal Health Co., Ltd., for their help in the preparation of this paper. This study was supported in part by a Grant-in-Aid for Scientific Research (KAKENHI, grant number 23580277) from the Japan Society for the Promotion of Science (JSPS) to TN.

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The authors declare that they have no competing interests.

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TN and SH conceived and designed the experiments. TN, SH, and NN performed the experiments. TN, SH, and NN analyzed the data. TN wrote the paper.

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Correspondence to Toshiki Nakano.

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Nakano, T., Hayashi, S. & Nagamine, N. Effect of excessive doses of oxytetracycline on stress-related biomarker expression in coho salmon. Environ Sci Pollut Res 25, 7121–7128 (2018). https://doi.org/10.1007/s11356-015-4898-4

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