Nitric oxide levels in brain, liver, and gills of silver catfish (Rhamdia quelen) exposed to the antiparasitic eprinomectin


Nitric oxide (NO) is a mediator and biomarker of pro- and anti-inflammatory processes. Excessive levels of NO for long periods have been associated with inflammation and tissue damage. The metabolism and synthesis of NO is usually measured indirectly, as metabolites and enzymes involved in reactions, often as the nitrite/nitrate (NOx) level. The aim of the present study was to measure the NOx levels in vital organs of juvenile silver catfish (Rhamdia quelen) exposed to various levels of eprinomectin in the water. The fish were exposed for 24 and 48 h to start concentration (0 h) of eprinomectin in water (0.0, 1.12, 1.80, and 3.97 μg/L). The eprinomectin concentrations in water were lower at 24 h (0.0, 0.85, 1.14, and 1.15 μg/L) and 48 h (0.0, 0.39, 0.69, and 1.28 μg/L), due to the process of eprinomectin metabolization. Subsequently, the fish were left for 48 h of recovery in eprinomectin-free water. NO levels were measured indirectly, as NOx levels in brain, liver, and gill tissue. Within 24 h of exposure, there was no significant increase in NOx levels in the organs evaluated at any of the concentrations tested. However, increases in NOx levels did occur at 48 h of exposure in all organs, particularly at the two highest concentrations of eprinomectin (1.80 and 3.97 μg/L). The transfer of fish to eprinomectin-free water did not result in reversal of NOx levels after 48 h of recovery, especially in fish that had been exposed to the two highest concentrations in the brain and liver tissues, and for the highest concentration in the gills. We conclude that silver catfish exposed to eprinomectin for up to 48 h present possible cerebral, hepatic, and branchial inflammatory process associated with increased tissue NOx levels, and that recovery for 48 h in water without antiparasitic is insufficient for the fish to recover from the poisoning.

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  1. Alak G, Yeltekin AÇ, Tas IH, Ucar A, Parlak V, Topal A, Kocaman EM, Atamanalp M (2017) Investigation of 8-OHdG, CYP1A, HSP70 and transcriptional analyses of antioxidant defense system in liver tissues of rainbow trout exposed to eprinomectin. Fish Shellfish Immunol 65:136–144.

    Article  PubMed  Google Scholar 

  2. Bahadoran Z, Carlstrom M, Mirmiran P, Ghasemi A (2020) Nitric oxide: to be or not to be an endocrine hormone? Acta Physiol 229:e13443.

    Article  Google Scholar 

  3. Baldissera MD, Souza CF, Doleski PH, Moreira KLS, Da Rocha MIUM, Da Veiga ML, Santos RCV, Baldisserotto B (2017) Xanthine oxidase activity exerts a pro-oxidant and pro-inflammatory profile in gills of experimentally infected silver catfish with Streptococcus agalactiae. Aquaculture 477:71–75.

    Article  Google Scholar 

  4. Baldissera MD, Souza CF, Descovi SN, Zanella R, Stefani LM, Da Silva AS, Baldisserotto B (2018a) Purinergic signalling as a potential pathway for trichlorfon induced-inflammation and impairment of the immune response using freshwater silver catfish. Aquaculture 497:91–96.

  5. Baldissera MD, Souza CF, Santos RCV, Baldisserotto B (2018b) Purinergic system displays an anti-inflammatory profile in serum of silver catfish experimentally infected with Streptococcus agalactiae: an attempt to ameliorate the inflammatory response. Microb Pathog 114:193–196.

  6. Da Cunha MA, Zeppenfeld CC, Garcia LO, Loro VL, Da Fonseca MB, Emanuelli T, Veeck APL, Copatti CE, Baldisserotto B (2010) Anesthesia of silver catfish with eugenol: time of induction, cortisol response and sensory analysis of fillet. Ciência Rural 40:2107–2114.

    Article  Google Scholar 

  7. Flora Filho R, Zilberstein B (2000) Óxido nítrico: o simples mensageiro percorrendo a complexidade. Metabolismo, síntese e funções. Rev Assoc Méd Bras 46:265–271.

    Article  PubMed  Google Scholar 

  8. Kozan E, Sevimli FK, Birdane FM, Adanir R (2008) Efficacy of eprinomectin against Toxocara canis in dogs. Parasitol Res 102(397–400):2008–2400.

    Article  Google Scholar 

  9. Kvaternick V, Kellermann M, Knaus M, Rehbein S, Rosentel J (2014) Pharmacokinets and metabolism of eprinomectin in cats when administered in a novel topical combination of fipronil, (S)-methoprene, eprinomection and praziquantel. Vet Parasitol 202:2–9.

    Article  PubMed  Google Scholar 

  10. Maharajan K, Muthulakshmi S, Nataraj B, Ramesh M, Kadirvelu K (2018) Toxicity assessment of pyriproxyfen in vertebrate model zebrafish embryos (Danio rerio): a multi biomarker study. Aquat Toxicol 196:132–145.

    Article  PubMed  Google Scholar 

  11. Merck (1996) Ivomec Eprinex (eprinomectin) pour-on for beef and dairy cattle: environmental assessment. Report NADA 141-079EA. Merck and Company, Rahway

    Google Scholar 

  12. Ozdemir S, Altun S, Arslan H (2018) Imidacloprid exposure cause the histopathological changes, activation of TNF-α, iNOS, 8-OHdG biomarkers, and alteration of caspase 3, iNOS, CYP1A, MT1 gene expression levels in common carp (Cyprinus carpio L.). Toxicol Rep 5:125–138.

    Article  PubMed  Google Scholar 

  13. Rao MR, Kanji VK, Sekhar V (1999) Pesticide induced changes of nitric oxide synthase in rat brain in vitro. Drug Chem Toxicol 22:411–420.

    Article  PubMed  Google Scholar 

  14. Serafini S, Soares JG, Perosa CF, Picoli F, Segat JC, Da Silva AS, Baretta D (2019a) Eprinomectin antiparasitic affects survival, reproduction and behavior of Folsomia candida biomarker, and its toxicity depends on the type of soil. Environ Toxicol Pharmacol 72:103262.

  15. Serafini S, Souza CF, Baldissera MD, Baldisserotto B, Picoli F, Segat JC, Baretta D, Da Silva AS (2019b) Fish exposed to eprinomectin show hepatic oxidative stress and impairment in enzymes of the phosphotransfer network. Aquaculture 508:199–205.

  16. Serafini S, Souza CF, Baldissera MD, Baldisserotto B, Segat JC, Baretta D, Zanella R, Da Silva AS (2019c) Fish exposed to water contaminated with eprinomectin show inhibition of the activities of AChE and Na+/K+-ATPase in the brain, and changes in natural behavior. Chemosphere 223:124–130.

  17. Souza CF, Baldissera MD, Moreira KLS, Da Rocha MIUM, Da Veiga ML, Santos RCV, Baldisserotto B (2017) Involvement of xanthine oxidase activity with oxidative and inflammatory renal damage in silver catfish experimentally infected with Streptococcus agalactiae: interplay with reactive oxygen species and nitric oxide. Microb Pathog 111:1–5.

    Article  PubMed  Google Scholar 

  18. Tatsch E, Bochi GV, Pereira RS, Kober H, Agertt VA, De Campos MMA, Gomes P, Duarte MMMF, Moresco RN (2011) A simple and inexpensive automated technique for measurement of serum nitrite/nitrate. Clin Biochem 44:348–350.

    Article  PubMed  Google Scholar 

  19. Thomas DD, Ridnour LA, Isenberg JS, Flores-Santana W, Switzer CH, Donzellie S, Hussain P, Vecoli C, Paolocci N, Ambs S, Colton C, Harris C, Roberts DD, Wink DA (2008) The chemical biology of nitric oxide. Implications in cellular signaling. Free Radic Biol Med 45:18–31.

    Article  PubMed  PubMed Central  Google Scholar 

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The authors would like to thank the CAPES (Brazil) and CNPq (Brazil) for their technical and financial support.

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Correspondence to Aleksandro Schafer Da Silva.

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This study was approved by the Ethical and Animal Welfare Committee of the Universidade do Estado de Santa Catarina (protocol number 4679260518).

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Serafini, S., de Freitas Souza, C., Baldissera, M.D. et al. Nitric oxide levels in brain, liver, and gills of silver catfish (Rhamdia quelen) exposed to the antiparasitic eprinomectin. Fish Physiol Biochem (2020).

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  • Avermectin
  • Environmental contamination
  • Impairment of organ functions
  • Freshwater fish
  • Vital organs