Cytogenetic effects of rifampicin in somatic and germinal cells of the mouse

The necessity to minimize adverse effects of tuberculosis chemotherapy requires a comprehensive evaluation of the effects of antituberculosis drugs on the reproductive system and testicular cell macromolecules. The epidemiological situation of tuberculosis in Central and Eastern Europe is getting worse. Data on adverse effects of antituberculosis drugs are scare concerning particularly their effects on the reproductive system. The aim of the present study was to investigate the potential effect of ethambutol, rifampicin, isoniazid and pyrazinamide co-administration on lipid peroxidation, glutathione content and protein SH-groups, DNA fragmentation levels, the reproductive capacity of Wistar male rats and the antenatal development of their posterity. The rats (150–170 g) were divided into two groups: group I – received antituberculosis drugs suspended in 1% starch gel per os: ethambutol – 155 mg/kg b.w./day, rifampicin – 74.4 mg/kg b.w./day, isoniazid – 62 mg/kg b.w./day, pyrazinamide – 217 mg/kg b.w./day, group II (control) – received only starch gel in corresponding volumes. The contents of TBA-active compounds, glutathione and protein SH-groups in testis and sperm were determined spectrophotometrically, the DNA-fragmentation was determined using an UV transilluminator (BIORAD, USA), reproductive system indices were measured by standard methods. The co-administration of therapeutic doses of ethambutol, isoniazid, rifampicin and pyrazinamide to male rats during the period of spermatogenesis caused an increase in the rate of thiobarbituric acid reactive substances formation in testis and sperm, decrease of testis glutathione and protein SH-group contents, significant changes in DNA fragmentation, fatal decrease of male fertilizing capacity and fertility, and increase of pre- and post-implantation embryo lethality. The changes in reproductive indices could be the result of direct or indirect effects of one or more drugs investigated.

show abstract

“…and a number of chromosomal aberrations of spermatocytes at the dose of 80 mg/kg b.w. (Aboul-Ela, 1995). …”

Section: Discussionmentioning

confidence: 99%

Damage of testicular cell macromolecules and reproductive capacity of male rats following co-administration of ethambutol, rifampicin, isoniazid and pyrazinamide

Shayakhmetova¹,

Bondarenko²,

Коваленко³

2012

Interdisciplinary Toxicology

View full text Add to dashboard Cite

show abstract

“…Genotoxic effect of these antibiotics were determined by various test systems (CA test, micronucleus test, SCE investigations and so on). These effects are as follows: Broken chromosome, micronucleus, various translocations, X-linked gene mutation in Drosophila, pause of meiotic division, dominant lethal mutations and SCEs (Promchainant 1975, Mace Jr. et al 1978, RaskO et al 1979, Meiying et al 1982, Nicoloff et al 1982, Richardson et al 1984, Singh and D'Ambrosio 1984, Sora et al 1984, Clements et al 1990, Hayashi et al 1990, Mavournin et al 1990, Odagiri et al 1990, Roselli et al 1990, Koldamova and Lefterov 1991, Miller 1991, Nersessian et al 1991, Risley and Pohorenec 1991, van Pelt et al 1991, Sudman et al 1992, Aboul-Ela 1995, Hoffmann et al 1995. These antibiotics have caused chromosomal and gene mutations due to direct effect on DNA.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Genotoxic Effects of Spiramycin in Rat Bone Marrow Cells.

İla

Topaktaş

1999

CYTOLOGIA

View full text Add to dashboard Cite

Summary The aim of this study was to investigate the genotoxic effects of spiramycin which is an effective ingredient of the antibiotic rovamycine in bone marrow cells of rats (Rattus norvegicus var. albinos). The rats were treated with 100, 200, 400 mg/kg bwt/day of spiramycin. Animals were treated with the above concentrations for 7 days and the bone marrow preparations were prepared after 6 and 12 h from the last administration. In 100 mg/kg bwt/day, spiramycin increased the percentages of the abnormal cells and the chromosomal aberration per cell (CA/cell) in the bone marrow cells of rats that were sacrificed after 6 h from the last administration. It could not induce the abnormalities however at the other concentrations (200 and 400 mg/kg bwt/day). The mitotic index (MI) was not decreased by any treatment of spiramycin. Spiramycin did not increase neither the percentage of abnormal cells nor the CA/cell in bone marrow cells of rats which sacrificed after 12 h from the last administration, whereas it generally decreased the MI in this treatment. Spiramycin did not affect the formation of chromosomal gaps.

show abstract

“…The other macrolide antibiotic, miokamycin, was not mutagenic against S. typhimurium strains TA98, TA100, TA1535, and TA1538, both with and without S9 mix, and also did not induce dominant lethal mutations in mice [6]. It was reported that many groups of antibiotic induced CAs, SCEs, and micronuclei in both in vitro and in vivo test systems, and also have a mutagenic effect against various strains of S. typhimurium [7][8][9][10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

No significant increase in chromosome aberrations and sister chromatid exchanges in cultured human lymphocytes treated with spiramycin

Rencüzoğulları¹,

İla²,

Topaktaş³

et al. 2001

Teratog Carcinog Mutagen

View full text Add to dashboard Cite

In this study, the chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) were investigated in human lymphocytes treated with spiramycin antibiotic (trade name, rovamycin). Spiramycin did not induce the CAs and SCEs, and also did not decrease the mitotic index (MI). However, spiramycin decreased the replication index (RI) only at 48 h treatment times. Teratogenesis Carcinog. Mutagen. 22:51-58, 2002.

show abstract

Cytogenetic effects of rifampicin in somatic and germinal cells of the mouse

Cited by 17 publications

References 2 publications

Damage of testicular cell macromolecules and reproductive capacity of male rats following co-administration of ethambutol, rifampicin, isoniazid and pyrazinamide

Damage of testicular cell macromolecules and reproductive capacity of male rats following co-administration of ethambutol, rifampicin, isoniazid and pyrazinamide

In Vivo Genotoxic Effects of Spiramycin in Rat Bone Marrow Cells.

No significant increase in chromosome aberrations and sister chromatid exchanges in cultured human lymphocytes treated with spiramycin

Contact Info

Product

Resources

About