The aim of the present study was to investigate the effect of Tributyltin (TBT) on brain function and neurotoxicity of freshwater teleost. The effects of long-term exposure to TBT on antioxidant related indices (MDA, malondialdehyde; SOD, superoxide dismutase; CAT, catalase; GR, glutathione reductase; GPx, glutathione peroxidase), Na+-K+-ATPase and neurological parameters (AChE, acetylcholinesterase; MAO, monoamine oxidase; NO, nitric oxide) in the brain of common carp were evaluated. Fish were exposed to sublethal concentrations of TBT (75 ng/L, 0.75 μg/L and 7.5 μg/L) for 15, 30, and 60 days. Based on the results, a low level and short-term TBT-induced stress could not induce the notable responses of the fish brain, but long-term exposure (more than 15 days) to TBT could lead to obvious physiological-biochemical responses (based on the measured parameters). The results also strongly indicated that neurotoxicity of TBT to fish. Thus, the measured physiological responses in fish brain could provide useful information to better understand the mechanisms of TBT-induced bio-toxicity.

Key Laboratory of Freshwater Biodiversity Conservation Yangtze River Fisheries Research Institute Chinese Academy of Fishery Sciences Wuhan 430223 China

Key Laboratory of Freshwater Biodiversity Conservation Yangtze River Fisheries Research Institute Chinese Academy of Fishery Sciences Wuhan 430223 China; University of South Bohemia in Ceske Budejovice Faculty of Fisheries and Protection of Waters South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses Research Institute of Fish Culture and Hydrobiology Zátiší 728 2 389 25 Vodňany Czech Republic

See more in PubMed

Mortensen AS, Arukwe A (2007) Modulation of xenobiotic biotransformation system and hormonal responses in Atlantic salmon (Salmo salar) after exposure to tributyltin (TBT). Comp Biochem Physiol C-Toxicol Pharmacol 145: 431–441. PubMed

Antizar-Ladislao B (2008) Environmental levels, toxicity and human exposure to tributyltin (TBT)-contaminated marine environment. a review. Environ Int 34: 292–308. PubMed

Gao JM, Hu JY, Zhen H, Yang M, Li BZ (2006) Organotin compounds in the Three Gorges Reservoir region of the Yangtze River. Bull Environ Contam Toxicol 76: 155–162. PubMed

Morcillo Y, Porte C (2000) Evidence of endocrine disruption in clams—Ruditapes decussata—transplanted to a tributyltin-polluted environment. Environ Pollut 107: 47–52. PubMed

Nakayama K, Oshima Y, Yamaguchi T, Tsuruda Y, Kang IJ, Kobayashi M, et al. (2004) Fertilization success and sexual behavior in male medaka, Oryzias latipes, exposed to tributyltin. Chemosphere 55: 1331–1337. PubMed

Zhang J, Zuo Z, Chen Y, Zhao Y, Hu S, Wang C (2007) Effect of tributyltin on the development of ovary in female cuvier (Sebastiscus marmoratus). Aquat Toxicol 83: 174–179. PubMed

St-Jean SD, Pelletier E, Courtenay SC (2002) Very low levels of waterborne butyltins modulate hemocyte function in the blue mussel Mytilus edulis . Mar Ecol Prog Ser 236: 155–161.

Horiguchi T (2006) Masculinization of female gastropod mollusks induced by organotin compounds, focusing on mechanism of actions of tributyltin and triphenyltin for development of imposex. Environ Sci 13: 77–87. PubMed

Porte C, Janer G, Lorusso LC, Ortiz-Zarragoitia M, Cajaraville MP, Fossi MC, et al. (2006) Endocrine disruptors in marine organisms: approaches and perspectives. Comp Biochem Physiol C-Toxicol Pharmacol 143: 303–315. PubMed

Mitra S, Siddiqui WA, Khandelwal S (2014) Differential susceptibility of brain regions to tributyltin chloride toxicity. Environ Toxicol 10.1002/tox.22009 PubMed DOI

Park K, Kim R, Park JJ, Shin HC, Lee JS, Cho HS, et al. (2012) Ecotoxicological evaluation of tributyltin toxicity to the equilateral venus clam, Gomphina veneriformis (Bivalvia: Veneridae). Fish Shellfish Immunol 32: 426–433. 10.1016/j.fsi.2011.11.031 PubMed DOI

Lushchak VI (2011) Environmentally induced oxidative stress in aquatic animals. Aquat Toxicol 101: 13–30. 10.1016/j.aquatox.2010.10.006 PubMed DOI

Li ZH, Zlabek V, Grabic R, Li P, Machova J, Velisek J, et al. (2010) Effects of exposure to sublethal propiconazole on the antioxidant defense system and Na+-K+-ATPase activity in brain of rainbow trout, Oncorhynchus mykiss . Aquat Toxicol 98: 297–303. 10.1016/j.aquatox.2010.02.017 PubMed DOI

Li ZH, Zlabek V, Velisek J, Grabic R, Machova J, Randak T (2010) Modulation of antioxidant defence system in brain of rainbow trout (Oncorhynchus mykiss) after chronic carbamazepine treatment. Comp Biochem Physiol C 151: 137–141. 10.1016/j.cbpc.2009.09.006 PubMed DOI

Sahin E, Gumuslu S (2004) Alterations in brain antioxidant status, protein oxidation and lipid peroxidation in response to different stress models. Behav Brain Res 155: 241–248. PubMed

Liu CM, Zheng GH, Ming QL, Sun JM, Cheng C (2013) Protective effect of puerarin on lead-induced mouse cognitive impairment via altering activities of acetyl cholinesterase, monoamine oxidase and nitric oxide synthase. Environ Toxicol Pharmacol 35: 502–510. 10.1016/j.etap.2013.02.009 PubMed DOI

Holmqvist B, Ekstrom P (1997) Subcellular localization of neuronal nitric oxide synthase in the brain of a teleost; an immunoelectron and confocal microscopical study. Brain Res 745: 67–82. PubMed

Rodriguez de Lores A, Alberici M, De Robertis E (1967) Ultrastructural and enzymic studies of cholinergic and non-cholinergic synaptic membranes isolated from brain cortex. J Neurochem 14: 215–225. PubMed

Balestrino M, Young J, Aitken P (1999) Block of (Na+,K+)ATPase with ouabain induces spreading depression-like depolarization in hippocampal slices. Brain Res 838: 37–44. PubMed

McCord JM, Fridovich I (1969) Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244: 6049–6055. PubMed

Goth L (1991) A simple method for determination of serum catalase activity and revision of reference range. Clin Chim Acta 196: 143–151. PubMed

Carlberg I, Mannervik B (1975) Purification and characterization of flavoenzyme glutathione reductase from rat liver. J Biol Chem 250: 5475–5480. PubMed

Lawrence RA, Burk RF (1976) Glutathione peroxidase activity in selenium deficient rat liver. Biochem Biophys Res Commun 71: 952–958. PubMed

Jain SK, McVie R, Duett J, Herbst JJ (1989) Erythrocyte membrane lipid peroxidation and glycosylated hemoglobin in diabetes. Diabetes 38: 1539–1543. PubMed

Agrahari S, Gopal K (2008) Inhibition of Na+-K+-ATPase in different tissues of freshwater fish Channa punctatus (Bloch) exposed to monocrotophos. Pest Biochem Physiol 92: 57–60.

Ellman GL, Courtney KD, Andres V Jr., Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7: 88–95. PubMed

Tabakoff B, Alivasatos SG (1972) Modified method for spectrophotometric determination of monoamine oxidase activity. Anal Chem 44: 427–428. PubMed

Stuehr DJ, Kwon NS, Gross SS, Thiel BA, Levi R, Nathan CF (1989) Synthesis of nitrogen oxides from L-arginine by macrophage cytosol: requirement for inducible and constitutive components. Biochem Biophys Res Commun 161: 420–426. PubMed

Beliaeff B, Burgeot T (2002) Integrated biomarker response: A useful tool for ecological risk assessment. Environ Toxicol Chem 21: 1316–1322. PubMed

Broeg K, Lehtonen KK (2006) Indices for the assessment of environmental pollution of the Baltic Sea coasts: Integrated assessment of a multi-biomarker approach. Mar Pollut Bull 53: 508–522. PubMed

Kavitha P, Rao JV (2009) Sub-lethal effects of profenofos on tissue-specific antioxidative responses in a Euryhyaline fish, Oreochromis mossambicus . Ecotoxicol Environ Saf 72: 1727–1733. 10.1016/j.ecoenv.2009.05.010 PubMed DOI

Livingstone DR (2001) Contaminant-stimulated reactive oxygen species production and oxidative damage in aquatic organisms. Mar Pollut Bull 42: 656–666. PubMed

Casalino E, Calzaretti G, Sblano C, Landriscina C (2002) Molecular inhibitory mechanisms of antioxidant enzymes in rat liver and kidney by cadmium. Toxicology 179: 37–50. PubMed

Zhang J, Zuo Z, Chen R, Chen Y, Wang C (2008) Tributyltin exposure causes brain damage in Sebastiscus marmoratus . Chemosphere 73: 337–343. 10.1016/j.chemosphere.2008.05.072 PubMed DOI

Rajeshkumar S, Mini J, Munuswamy N (2013) Effects of heavy metals on antioxidants and expression of HSP70 in different tissues of Milk fish (Chanos chanos) of Kaattuppalli Island, Chennai, India. Ecotox Environ Safe 98: 8–18. PubMed

Pandey S, Parvez S, Sayeed I, Haque R, Bin-Hafeez B, Raisuddin S (2003) Biomarkers of oxidative stress: a comparative study of river Yamuna fish Wallago attu (Bl. & Schn.). Sci Total Environ 309: 105–115. PubMed

John S, Kale M, Rathore N, Bhatnagar D (2001) Protective effect of vitamin E in dimethoate and malathion induced oxidative stress in rat erythrocytes. Journal of Nutritional Biochemistry 12: 500–504. PubMed

Zhang X, Yang F, Zhang X, Xu Y, Liao T, Song S, et al. (2008) Induction of hepatic enzymes and oxidative stress in Chinese rare minnow (Gobiocypris rarus) exposed to waterborne hexabromocyclododecane (HBCDD). Aquat Toxicol 86: 4–11. PubMed

Li ZH, Zlabek V, Grabic R, Li P, Randak T (2010) Modulation of glutathione-related antioxidant defense system of fish chronically treated by the fungicide propiconazole. Comp Biochem Physiol C 152: 392–398. 10.1016/j.cbpc.2010.06.006 PubMed DOI

Tiano L, Fedeli D, Santoni G, Davies I, Falcioni G (2003) Effect of tributyltin on trout blood cells: changes in mitochondrial morphology and functionality. Biochim Biophys Acta-Mol Cell Res 1640: 105–112. PubMed

Tiano L, Fedeli D, Moretti M, Falcioni G (2001) DNA damage induced by organotins on trout-nucleated erythrocytes. Appl Organomet Chem 15: 575–580.

Aldridge WN, Street BW (1970) Oxidative phosphorylation. The specific binding of trimethyltin and triethyltin to rat liver mitochondria. Biochem J 118: 171–179. PubMed PMC

Gennari A, Viviani B, Galli CL, Marinovich M, Pieters R, Corsini E (2000) Organotins induce apoptosis by disturbance of [Ca(2+)](i) and mitochondrial activity, causing oxidative stress and activation of caspases in rat thymocytes. Toxicol Appl Pharmacol 169: 185–190. PubMed

Mitra S, Siddiqui WA, Khandelwal S (2014) Early cellular responses against tributyltin chloride exposure in primary cultures derived from various brain regions. Environ Toxicol Pharmacol 37: 1048–1059. 10.1016/j.etap.2014.03.020 PubMed DOI

Nesci S, Ventrella V, Trombetti F, Pirini M, Pagliarani A (2011) Tributyltin (TBT) and mitochondrial respiration in mussel digestive gland. Toxicol Vitro 25: 951–959. 10.1016/j.tiv.2011.03.004 PubMed DOI

Zhou J, Zhu XS, Cai ZH (2010) Tributyltin toxicity in abalone (Haliotis diversicolor supertexta) assessed by antioxidant enzyme activity, metabolic response, and histopathology. J Hazard Mater 183: 428–433. 10.1016/j.jhazmat.2010.07.042 PubMed DOI

Basha DC, Rani MU, Devi CB, Kumar MR, Reddy GR (2012) Perinatal lead exposure alters postnatal cholinergic and aminergic system in rat brain: reversal effect of calcium co-administration. Int J Dev Neurosci 30: 343–350. 10.1016/j.ijdevneu.2012.01.004 PubMed DOI

Devi CB, Reddy GH, Prasanthi RP, Chetty CS, Reddy GR (2005) Developmental lead exposure alters mitochondrial monoamine oxidase and synaptosomal catecholamine levels in rat brain. Int J Dev Neurosci 23: 375–381. PubMed

Reddy GR, Devi BC, Chetty CS (2007) Developmental lead neurotoxicity: alterations in brain cholinergic system. Neurotoxicology 28: 402–407. PubMed

Nava-Ruiz C, Alcaraz-Zubeldia M, Mendez-Armenta M, Vergara P, Diaz-Ruiz A, Rios C (2010) Nitric oxide synthase immunolocalization and expression in the rat hippocampus after sub-acute lead acetate exposure in rats. Exp Toxicol Pathol 62: 311–316. 10.1016/j.etp.2009.04.006 PubMed DOI

Kim S, Hyun J, Kim H, Kim Y, Kim E, Jang J, et al. (2011) Effects of lead exposure on nitric oxide-associated gene expression in the olfactory bulb of mice. Biol Trace Elem Res 142: 683–692. 10.1007/s12011-010-8791-1 PubMed DOI

Traystman RJ, Kirsch JR, Koehler RC (1991) Oxygen radical mechanisms of brain injury following ischemia and reperfusion. J Appl Physiol 71: 1185–1195. PubMed

Andersen JK (2004) Oxidative stress in neurodegeneration: cause or consequence? Nat Med 10 Suppl: S18–25. PubMed

Yadwad VB, Kallapur VL, Basalingappa S (1990) Inhibition of gill Na+- K+-atpase activity in dragonfly larva, Pantala flavesens, by endosulfan. Bull Environ Contam Toxicol 44: 585–589. PubMed

Samuel PM, Roy S, Jaiswal KA, Rao JV (1998) Differential effects of organometallic tin compounds on Na+/K+-ATPase activity. J Appl Toxicol 18: 383–386. PubMed

Elsabbagh HS, Moussa SZ, El-tawil OS (2002) Neurotoxicologic sequelae of tributyltin intoxication in rats. Pharmacol Res 45: 201–206. PubMed

Hartl MG, Hutchinson S, Hawkins LE (2001) Sediment-associated tri-n-butyltin chloride and its effects on osmoregulation of freshwater-adapted 0-group European flounder, Platichthys flesus (L.). Aquat Toxicol 55: 125–136. PubMed

Oruc EO, Uner N, Tamer L (2002) Comparison of Na+-K+-ATPase activities and malondialdehyde contents in liver tissue for three fish species exposed to azinphosmethyl. Bull Environ Contam Toxicol 69: 271–277. PubMed

Beliaeff B, Burgeot T (2002) Integrated biomarker response: A useful tool for ecological risk assessment. Environmental Toxicology and Chemistry 21: 1316–1322. PubMed

Kim WK, Lee SK, Jung J (2010) Integrated assessment of biomarker responses in common carp (Cyprinus carpio) exposed to perfluorinated organic compounds. J Hazard Mater 180: 395–400. 10.1016/j.jhazmat.2010.04.044 PubMed DOI

Li ZH, Velisek J, Zlabek V, Grabic R, Machova J, Kolarova J, et al. (2011) Chronic toxicity of verapamil on juvenile rainbow trout (Oncorhynchus mykiss): Effects on morphological indices, hematological parameters and antioxidant responses. J Hazard Mater 185: 870–880. 10.1016/j.jhazmat.2010.09.102 PubMed DOI

Feng M, Qu R, Li Y, Wei Z, Wang Z (2014) Biochemical biomarkers in liver and gill tissues of freshwater fish Carassius auratus following in vivo exposure to hexabromobenzene. Environ Toxicol 29: 1460–1470. 10.1002/tox.21876 PubMed DOI

Alteration of cytochrome P450 1 regulation and HSP 70 level in brain of juvenile common carp (Cyprinus carpio) after chronic exposure to tributyltin