title: Effects of treatment with the anti-parasitic drug diminazene aceturate on antioxidant enzymes in rat liver and kidney.
abstract: Diminazene aceturate (DA) is the active component of some trypanocidal drugs used for the treatment of animals infected with trypanosomosis and babesiosis. Residues of DA may cause hepatotoxic and nephrotoxic effects. Therefore, the purpose of this study was to investigate the occurrence of oxidative stress, i.e., changes in the antioxidant defense system of rats treated with a single dose of 3.5 mg kg(-1) of DA. All treatments were intramuscularly administered, and evaluations were performed on days 7 and 21 post-treatment (PT). Liver and kidney samples were collected and evaluated by histopathology and oxidative stress parameters (thiobarbituric acid-reactive species, catalase, superoxide dismutase, carbonyl, non-protein thiols, and reduced glutathione). Finally, blood was collected to determine seric DA concentration. Superoxide dismutase (SOD) and catalase (CAT) activities in liver and kidney of rats were dramatically inhibited (p < 0.05) compared to the control group on day 21 PT. This difference is related to the concomitant increase (p < 0.05) in malondialdehyde (MDA) content, which was identified by an increase in thiobarbituric acid-reactive species (TBARS) levels. The carbonyl levels did not differ between groups (p > 0.05). Both non-protein thiols (NPSH) and glutathione (GSH) levels in liver and kidney decreased (p < 0.05) on day 21 PT. Chromatographic analyses showed lower levels of DA on day 21 PT compared to day 7 PT. A negative correlation was observed between DA concentration in serum and lipid peroxidation in liver and kidney tissues on 21 days PT. Histopathology revealed vacuolar degeneration in liver and kidney samples on day 21 PT. Our findings indicate that DA could cause oxidative damage to liver and kidney of rats.
authors.affiliation: Department of Microbiology and Parasitology, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil. matheusd.biomed@yahoo.com.br.
authors.forename: Matheus D
authors.initials: MD
authors.lastname: Baldissera
authors.affiliation: Department of Microbiology and Parasitology, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Gonçalves
authors.affiliation: Laboratory of Cell Culture, Centro Universitário Franciscano, Santa Maria, RS, Brazil.
authors.forename: Michele R
authors.initials: MR
authors.lastname: Sagrillo
authors.affiliation: Department of Microbiology and Parasitology, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil.
authors.forename: Thirssa H
authors.initials: TH
authors.lastname: Grando
authors.affiliation: Laboratory of Cell Culture, Centro Universitário Franciscano, Santa Maria, RS, Brazil.
authors.forename: Camila S
authors.initials: CS
authors.lastname: Ritter
authors.affiliation: Laboratory of Cell Culture, Centro Universitário Franciscano, Santa Maria, RS, Brazil.
authors.forename: Fabielly S
authors.initials: FS
authors.lastname: Grotto
authors.affiliation: Laboratory of Cell Culture, Centro Universitário Franciscano, Santa Maria, RS, Brazil.
authors.forename: Gerson F
authors.initials: GF
authors.lastname: Brum
authors.affiliation: Department of Microbiology and Parasitology, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil.
authors.forename: Sônia C A
authors.initials: SC
authors.lastname: da Luz
authors.affiliation: Department of Biochemistry, UFSM, Santa Maria, RS, Brazil.
authors.forename: Sergio O
authors.initials: SO
authors.lastname: Silveira
authors.affiliation: Laboratory of Cell Culture, Centro Universitário Franciscano, Santa Maria, RS, Brazil.
authors.forename: Viviane P
authors.initials: VP
authors.lastname: Fausto
authors.affiliation: Laboratory of Phytochemistry, UFSM, Santa Maria, RS, Brazil.
authors.forename: Aline A
authors.initials: AA
authors.lastname: Boligon
authors.affiliation: Laboratory of Cell Culture, Centro Universitário Franciscano, Santa Maria, RS, Brazil.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Vaucher
authors.affiliation: Department of Animal Science, Universidade do Estado de Santa Catarina (UDESC), Chapecó, SC, Brazil.
authors.forename: Lenita M
authors.initials: LM
authors.lastname: Stefani
authors.affiliation: Department of Animal Science, Universidade do Estado de Santa Catarina (UDESC), Chapecó, SC, Brazil.
authors.forename: Aleksandro S
authors.initials: AS
authors.lastname: da Silva
authors.affiliation: Department of Physiology and Pharmacology, UFSM, Santa Maria, RS, Brazil.
authors.forename: Carine F
authors.initials: CF
authors.lastname: Souza
authors.affiliation: Department of Microbiology and Parasitology, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil.
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Monteiro
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D000977:Antiparasitic Agents / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D004133:Diminazene / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
chemical_list: D000975:Antioxidants; D000977:Antiparasitic Agents; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D004133:Diminazene
keywords: Antioxidant system; Diminazene aceturate; Lipid peroxidation; Oxidative damage; Serum
references.citation: Methods Enzymol. 1994;233:357-63
references.pmid: 8015470
references.citation: Pharmacol Res. 2015 Dec;102:138-57
references.pmid: 26470648
references.citation: Trop Med Parasitol. 1985 Dec;36(4):199-204
references.pmid: 4089474
references.citation: Science. 1983 Apr 29;220(4596):472-7
references.pmid: 6836290
references.citation: Ecotoxicology. 2013 Oct;22(8):1241-54
references.pmid: 23943211
references.citation: J S Afr Vet Assoc. 2000 Sep;71(3):180-6
references.pmid: 11205168
references.citation: Antimicrob Agents Chemother. 1998 Nov;42(11):2858-62
references.pmid: 9797216
references.citation: Am J Physiol Regul Integr Comp Physiol. 2011 Oct;301(4):R843-63
references.pmid: 21775650
references.citation: Am J Clin Nutr. 1993 May;57(5 Suppl):715S-724S; discussion 724S-725S
references.pmid: 8475889
references.citation: Methods Enzymol. 1984;105:121-6
references.pmid: 6727660
references.citation: Front Cell Infect Microbiol. 2013 Sep 18;3:53
references.pmid: 24066283
references.citation: J Pharm Biomed Anal. 2002 Nov 7;30(4):979-86
references.pmid: 12408888
references.citation: Acta Trop. 1993 Sep;54(3-4):185-203
references.pmid: 7902657
references.citation: Methods Enzymol. 1990;186:464-78
references.pmid: 1978225
references.citation: Antimicrob Agents Chemother. 2014 Aug;58(8):4713-7
references.pmid: 24914124
references.citation: Exp Parasitol. 2011 Jul;128(3):243-9
references.pmid: 21420954
references.citation: Toxicon. 2005 Mar 15;45(4):395-402
references.pmid: 15733560
references.citation: Biochem Pharmacol. 2002 Dec 1;64(11):1617-27
references.pmid: 12429351
references.citation: Environ Sci Pollut Res Int. 2015 Oct;22(20):15571-8
references.pmid: 26013742
references.citation: Ecol Lett. 2008 Nov;11(11):1238-51
references.pmid: 18803642
references.citation: Arch Biochem Biophys. 1959 May;82(1):70-7
references.pmid: 13650640
references.citation: Chemosphere. 2012 Jul;88(4):377-83
references.pmid: 22436588
references.citation: Chem Biol Interact. 2006 Mar 10;160(1):1-40
references.pmid: 16430879
references.citation: Mol Cell. 2012 Oct 26;48(2):158-67
references.pmid: 23102266
references.citation: Clin Chem. 1995 Dec;41(12 Pt 2):1819-28
references.pmid: 7497639
references.citation: Methods Mol Biol. 1998;108:347-52
references.pmid: 9921543
references.citation: J Biol Chem. 1969 Nov 25;244(22):6049-55
references.pmid: 5389100
references.citation: Anal Biochem. 1979 Jun;95(2):351-8
references.pmid: 36810
references.citation: Toxicol In Vitro. 2010 Jun;24(4):1148-57
references.pmid: 20214973
references.citation: Aquat Toxicol. 2011 Jan 17;101(1):13-30
references.pmid: 21074869
references.citation: Int J Parasitol Parasites Wildl. 2012 Nov 22;2:18-31
references.pmid: 24533312
references.citation: Biochem Pharmacol. 2007 May 15;73(10):1537-47
references.pmid: 17291457
references.citation: Drug Resist Updat. 2007 Feb-Apr;10(1-2):30-50
references.pmid: 17409013
references.citation: Ecotoxicology. 2012 Jul;21(5):1533-40
references.pmid: 22535316
references.citation: J Biol Chem. 1981 Nov 10;256(21):10930-3
references.pmid: 6270136