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Hydrogen peroxide treatment in Atlantic salmon induces stress and detoxification response in a daily manner.
Chronobiol Int 2016; 33(5):530-42CI

Abstract

Daily variation in the absorption, metabolism and excretion of toxic substances will ultimately determine the actual concentration to which the cells and tissues are exposed. In aquaculture, Atlantic salmon (Salmo salar) can be frequently exposed to hydrogen peroxide (H2O2) to treat topical skin and gill infections, particularly in relation to parasitic infections (e.g. sea lice Lepeophtheirus salmonis and amoebic gill disease caused by Neoparamoeba perurans). It is well accepted that the time of administration influences pharmacodynamics and pharmacokinetics of drugs which in turn affects their efficacy and toxicity. Consequently, a better understanding of drug side effects as a function of time of day exposure would help to improve treatment efficacy and fish welfare. To this end, salmon were exposed to H2O2 (1500 mg/L) for 20 min at six different times of the day during a 24-h cycle and we investigated the time-dependent effects of exposure on physiological stress (glucose, lactate and cortisol) and antioxidant enzyme expression (gpx1, cat, Mn-sod and hsp70) in liver and gills. In addition, at each sampling point, 8 control fish were also sampled. Our results revealed that the time of administration of H2O2 caused significant differences in the induction of both physiological and oxidative stress responses. Glucose and lactate were higher in the treated fish during daytime whereas cortisol levels appeared to be systematically increased (>1000 ng/mL) after H2O2 treatment irrespective of exposure time, although differences with control levels were higher during the day. In liver, gene expression of antioxidant enzymes displayed daily rhythmicity in both treated and control groups and showed higher mRNA expression levels in salmon treated with H2O2 at ZT6 (6 h after lights onset). In gills, rhythmic expression was only found for gpx1 in the control fish and for hsp70 and Mn-sod in the treated groups. However, in the treated salmon, higher gene expression levels of all the investigated enzymes were also observed at ZT6-10. Clock gene expression showed rhythmicity only in the liver in accordance with the daily rhythm of enzyme expression observed in this tissue. Altogether, this study provides first evidence of chronotoxicity in Atlantic salmon treated with H2O2 and suggests increased sublethal toxic effect during the first half of the day. These results have direct relevance to the salmon and broader aquaculture industry by optimising the timing of treatment administration, opening the door to chronotherapy to treat fish diseases.

Authors+Show Affiliations

a Genetics and Reproduction Group , Institute of Aquaculture, University of Stirling , Stirling , UK.a Genetics and Reproduction Group , Institute of Aquaculture, University of Stirling , Stirling , UK.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27058450

Citation

Vera, L M., and H Migaud. "Hydrogen Peroxide Treatment in Atlantic Salmon Induces Stress and Detoxification Response in a Daily Manner." Chronobiology International, vol. 33, no. 5, 2016, pp. 530-42.
Vera LM, Migaud H. Hydrogen peroxide treatment in Atlantic salmon induces stress and detoxification response in a daily manner. Chronobiol Int. 2016;33(5):530-42.
Vera, L. M., & Migaud, H. (2016). Hydrogen peroxide treatment in Atlantic salmon induces stress and detoxification response in a daily manner. Chronobiology International, 33(5), pp. 530-42. doi:10.3109/07420528.2015.1131164.
Vera LM, Migaud H. Hydrogen Peroxide Treatment in Atlantic Salmon Induces Stress and Detoxification Response in a Daily Manner. Chronobiol Int. 2016;33(5):530-42. PubMed PMID: 27058450.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydrogen peroxide treatment in Atlantic salmon induces stress and detoxification response in a daily manner. AU - Vera,L M, AU - Migaud,H, Y1 - 2016/04/08/ PY - 2016/4/9/entrez PY - 2016/4/9/pubmed PY - 2017/3/31/medline KW - Atlantic salmon KW - chronotherapy KW - chronotoxicity KW - daily rhythms KW - hydrogen peroxide KW - oxidative stress KW - stress response SP - 530 EP - 42 JF - Chronobiology international JO - Chronobiol. Int. VL - 33 IS - 5 N2 - Daily variation in the absorption, metabolism and excretion of toxic substances will ultimately determine the actual concentration to which the cells and tissues are exposed. In aquaculture, Atlantic salmon (Salmo salar) can be frequently exposed to hydrogen peroxide (H2O2) to treat topical skin and gill infections, particularly in relation to parasitic infections (e.g. sea lice Lepeophtheirus salmonis and amoebic gill disease caused by Neoparamoeba perurans). It is well accepted that the time of administration influences pharmacodynamics and pharmacokinetics of drugs which in turn affects their efficacy and toxicity. Consequently, a better understanding of drug side effects as a function of time of day exposure would help to improve treatment efficacy and fish welfare. To this end, salmon were exposed to H2O2 (1500 mg/L) for 20 min at six different times of the day during a 24-h cycle and we investigated the time-dependent effects of exposure on physiological stress (glucose, lactate and cortisol) and antioxidant enzyme expression (gpx1, cat, Mn-sod and hsp70) in liver and gills. In addition, at each sampling point, 8 control fish were also sampled. Our results revealed that the time of administration of H2O2 caused significant differences in the induction of both physiological and oxidative stress responses. Glucose and lactate were higher in the treated fish during daytime whereas cortisol levels appeared to be systematically increased (>1000 ng/mL) after H2O2 treatment irrespective of exposure time, although differences with control levels were higher during the day. In liver, gene expression of antioxidant enzymes displayed daily rhythmicity in both treated and control groups and showed higher mRNA expression levels in salmon treated with H2O2 at ZT6 (6 h after lights onset). In gills, rhythmic expression was only found for gpx1 in the control fish and for hsp70 and Mn-sod in the treated groups. However, in the treated salmon, higher gene expression levels of all the investigated enzymes were also observed at ZT6-10. Clock gene expression showed rhythmicity only in the liver in accordance with the daily rhythm of enzyme expression observed in this tissue. Altogether, this study provides first evidence of chronotoxicity in Atlantic salmon treated with H2O2 and suggests increased sublethal toxic effect during the first half of the day. These results have direct relevance to the salmon and broader aquaculture industry by optimising the timing of treatment administration, opening the door to chronotherapy to treat fish diseases. SN - 1525-6073 UR - https://www.unboundmedicine.com/medline/citation/27058450/Hydrogen_peroxide_treatment_in_Atlantic_salmon_induces_stress_and_detoxification_response_in_a_daily_manner_ L2 - http://www.tandfonline.com/doi/full/10.3109/07420528.2015.1131164 DB - PRIME DP - Unbound Medicine ER -