Genotoxicity evaluation of pyrazinamide in mice

Anitha, B.; Murthy, Sudha; Gopinath, P. M.; Durairaj, G.

doi:10.1016/0165-1218(94)90113-9

Cited by 11 publications

(5 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Levels and character of DNA fragmentation are markers of apoptotic processes in organism [32]. Our results on DNAfragmentation intensification in rat testis with diabetes and ATD co-administration are concordant with our previous data which demonstrated the presence of epigenetic effects following PZA administration in rats [31] and with the results of other authors indicating some negative ATD effects on chromosome structure and functioning [33]. Differences in DNA-fragmentation processes between diabetes with or without ATD coadministration could be caused by specific effects of these compounds on different nucleases activities [32].…”

Section: Discussionsupporting

confidence: 93%

“…We suggest that, in our experiment, the genotoxic effects of STZ added to the genotoxic effects of ATDs contributed to the increase of postimplantation embryo-lethality indices. This hypothesis is supported by the data of other authors' experiments on mice demonstrating weak genotoxicity of PZA at doses of 125, 250 and 500 mg/kg [33]. Moreover, other authors' in vitro experiments showed that an INH metabolite (monoacethylhydrazine) exhibited mutagenic actions [41].…”

Section: Discussionmentioning

confidence: 52%

See 1 more Smart Citation

Reproductive Disorders in Streptozotocin-Treated Male Rats Following Co-Administration of Ethambutol, Rifampicin, Isoniazid and Pyrazinamide

Shayakhmetova

Bondarenko

Matvienko

et al. 2012

Romanian Journal of Diabetes Nutrition and Metabolic Diseases

View full text Add to dashboard Cite

Objectives: To evaluate the effect of anti-tuberculosis drugs (ATD) on indices ofreproductive capability, DNA fragmentation and offspring development of male ratswith testicular malfunction caused by experimental diabetes. Materials and Methods: Wistar albino male rats (body weight 160-200 g) were divided into threegroups: I - control, II - streptozotocin diabetes, III - streptozotocin diabetes + ATD.The testis DNA fragmentation was determined electrophoretically; spermatogeneticindices, offspring antenatal and postnatal development indices - by standardprocedures. Morphological analyses of gonadic structures were carried out by opticmicroscopy. Results: The study of the effects of diabetes and ATD administration ontestis cells morphologic and morphometric parameters and spermatogenesissuggested the presence of specific diabetes- and anti tuberculosis drugs - mediatedquantitative and qualitative changes in male rat reproductive organs,spermatogenetic epithelial cells, level and character of DNA fragmentation incomparison with normal rats. These changes were accompanied by alterations inprocesses of fertilisation (with intact females), embryogenesis and by lowering ofoffspring survival. Conclusions: Observed changes could hence affect the state andcorrect functioning of spermatogenetic epithelium and of other tissues ofreproductive organs, as well as offspring development in diabetic rats.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 52%

Reproductive Disorders in Streptozotocin-Treated Male Rats Following Co-Administration of Ethambutol, Rifampicin, Isoniazid and Pyrazinamide

Shayakhmetova

Bondarenko

Matvienko

et al. 2012

Romanian Journal of Diabetes Nutrition and Metabolic Diseases

View full text Add to dashboard Cite

show abstract

“…This assumption could be confirmed by the data of experiments on mice demonstrating weak genotoxicity of pyrazinamide at doses of 125, 250 and 500 mg/kg b.w. (Anitha et al 1994). Moreover, in vitro experiments showed that one isoniazid metabolite – mono acethylhydrazine – increased the number of Salmonella typhimurium TA100 and TA1535 revertant mutations and the number of micronuclei in polychromatophylic erythrocytes, which could be evidence of its mutagenic action (Bhide et al 1984).…”

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

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

“…The genotoxic properties of INH in mammals are essentially determined by the pharmacokinetic behavior of the terminal reactive metabolite ( Braun et al, 1984 ). Anitha et al (1994) reported that PZA exhibited weak genotoxic effect on mice, but Arslan et al (2015) showed that PZA had strong hepatotoxic effects and caused DNA damage in rats. ETA has less toxic effects on organisms than other anti-TB drugs ( Bruton et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

The first-line antituberculosis drugs, and their fixed-dose combination induced abnormal sperm morphology and histological lesions in the testicular cells of male mice

Bakare

Moses

Beckely

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Rifampicin (RIF), Isoniazid (INH), Ethambutol (EMB), Pyrazinamide (PZA), and/or their fixed-dose combination (FDC) are extensively prescribed in the cure of Tuberculosis (TB) globally. In spite of the beneficial effect, these drugs are capable of inducing cellular toxicity. Existing information on the genotoxic effects of the first-line anti-TB drugs is limited and contentious. Herein, we evaluated the reproductive genotoxicity of RIF, INH, EMB, PZA, and their FDC utilizing the mouse sperm morphology assay. Histological examination of the testes of exposed mice was also performed. Male Swiss albino mice (11–13 weeks old) were intraperitoneally exposed for 5 consecutive days to each of the anti-TB drugs at four different doses of 6.25, 12.5, 25, and 50 mg/kg bw of PZA; 2.5, 5.0, 10, and 20 mg/kg bw of RIF; 1.25, 2.5, 5.0 and 10 mg/kg bw of INH; 3.75, 7.5, 15 and 30 mg/kg bw of EMB; and 7, 14, 28 and 56 mg/kg bw of FDC corresponding respectively to ×0.25, ×0.5, ×1 and ×2.0 of the standard daily dose. In comparison with the negative control (normal saline), there was no significant difference in the testicular weight and organo-somatic index of exposed mice. There was an increase (p > 0.05) in the frequency of abnormal spermatozoa at most of the tested doses of each drug and a dose-dependent decrease with the FDC. Each of the anti-TB drugs except the FDC induced pathological lesions in the testes. These findings suggest that the individual first-line anti-TB drug unlike the FDC has the potential to provoke testicular anomalies in male mice.

show abstract

Genotoxicity evaluation of pyrazinamide in mice

Cited by 11 publications

References 7 publications

Reproductive Disorders in Streptozotocin-Treated Male Rats Following Co-Administration of Ethambutol, Rifampicin, Isoniazid and Pyrazinamide

Reproductive Disorders in Streptozotocin-Treated 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

The first-line antituberculosis drugs, and their fixed-dose combination induced abnormal sperm morphology and histological lesions in the testicular cells of male mice

Contact Info

Product

Resources

About