Examination of Carbadox genotoxicity in vitro and in vivo

Abstract

Due to its bactericidal activity Carbadox is used for treatment of swine dysentery and salmonellosis. Also, it can be used as a factor for growth stimulation. Carbadox is the only drug for certain health problems in swine production. At the same time Carbadox is slowly metabolized. The aim of this work was an examination of Carbadox genotoxicity in vivo and in vitro. In vitro genotoxicity of different doses of Carbadox was examined on cultured human peripheral blood lymphocytes. Damage to chromosomal DNA was observed under the microscope as sister chromatid exchanges (SCEs). In vivo genotoxicity of Carbadox was examined on metaphase chromosomes from bone marrow cells of BALB/c strain male mice. Experimental animals were intragastrically treated with three different doses of Carbadox. In addition there were negative and a positive control groups of mice. Animals in the positive control were treated with a known clastogenic agent, cyclophosphamide, in a dose of 0,4 mg/kg b.w. In vivo genotoxicity of Carbadox was examined through eight experimental cycles. The results showed that this preparation with an antimicrobial mode of action induced damage to chromosomal DNA in human lymphocytes as well as structural and numerical chromosomal changes in bone marrow cells of BALB/c mice. All the examined concentrations of Carbadox significantly increased SCEs and consistently manifested a dose-dependent pattern. Also, all the examined doses caused karyotypic changes in vivo inducing numerical and structural chromosomal aberrations in mouse bone marrow cells. There was a positive correlation between the number of bone marrow cells with cytogenetic changes and the dose of Carbadox. It could be concluded that Carbadox expressed potential genotoxicity, especially at the highest investigated doses.

Carbadox je sintetsko organsko jedinjenje (Metil-3(2quinoksal-metilen) karbozat-N1-N4 dioksid) sa baktericidnim dejstvom koje se koristi u suzbijanju svinjske dizenterije i salmoneloze i kao faktor koji stimuliše rast. Zbog spore metaboličke obrade i dugog zadržavanja u organizmu tretiranih životinja, a još vise zbog njegovog toksičnog, citotoksičnog i kancerogenog dejstva, Carbadox u novije vreme predmet detaljnih proučavanja. U ovom radu su izneti rezultati in vitro ispitivanja efekta Carbadoxa na limfocite periferne krvi čoveka praćenjem promena na nivou molekula DNK na osnovu učestalosti razmene sestrinskih hromatida. Citogenetička ispitivanja uticaja Carbadoxa, posle intragastrične aplikacije, na nastanak hromozomskih promena u ćelijama kostne srži obavljena su na miševima BALB/c soja. Hromozomi za kariotipsku analizu su dobijeni korišćenjem direktne metode ispiranja srži dugih cevastih kostiju. Rezultati ispitivanja efekata različitih doza Carbadoxa in vitro na limfocitima čoveka i in vivo na ćelijama kostne srži miševa BALB/c ukazali su da ovaj antibiotik poseduje visok genotoksični potencijal i jasno manifestuje mutageni efekat.