Metronidazole hprt mutation induction in sheep and the relationship with its elimination rate

Ostrosky‐Wegman, Patricia; Asseff, Ismael Lares; Santiago, Pilar; Elizondo, Guillermo; Montero, Regina

doi:10.1016/0027-5107(94)90299-2

Cited by 12 publications

(5 citation statements)

References 27 publications

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“…However, several publications have reported the development of resistance to the drug in E. histolytica [14,15,23], similar to other intestinal protozoan parasites such as Giardia lamblia and Trichomonas vaginalis [24,25]. Besides, MTZ has shown carcinogenic potential in animal studies [26] and many collateral effects, mainly gastrointestinal [13]. Plants have been widely used for the identification and isolation of compounds with anti-amoebic properties and more than a hundred extracts and derived compounds with variable activity have been reported [27].…”

Section: Discussionmentioning

confidence: 99%

Anti-amoebic Activity of Leaf Extracts and Aporphine Alkaloids Obtained from Annona purpurea

et al. 2020

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Annona purpurea has been traditionally used by indigenous and socioeconomically disadvantaged people to treat infectious and parasitic diseases, including amoebiasis. The goal of this study was to assess the effect of a crude methanolic extract, an alkaloid extract, and aporphine alkaloids from leaves of A. purpurea on the viability of Entamoeba histolytica trophozoite cultures and to identify the mechanism of action. Different concentrations of the extracts and alkaloids purpureine (1), 3-hydroxyglaucine (2), norpurpureine (3) glaziovine (4), and oxopurpureine (5) were added to the cultures, and dead parasites were counted after 24 h using a tetrazolium dye reduction assay and analyzed by flow cytometry. The crude extract did not affect the viability of amoebae, but the alkaloid extract and the derived alkaloid glaziovine (4) had important anti-amoebic activity with an IC50 of 33.5 µM compared to that shown by metronidazole (6.8 µM). The treatments induced significant morphological changes in the trophozoites, and most parasites killed by the alkaloid extract were positive for Annexin V, suggesting that apoptosis was the main mechanism of action. In contrast, glaziovine (4) induced less apoptosis with more amoebic lysis. This study supports the idea that aporphine alkaloids from A. purpurea, mainly (+)-(R)-glaziovine (4), could contribute to the development of new formulations for the treatment of amoebiasis. In addition, X-ray diffraction structural analysis and complete 1H and 13C NMR assignments of (+)-(R)-glaziovine (4) were performed and reported for the first time.

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Section: Discussionmentioning

confidence: 99%

Anti-amoebic Activity of Leaf Extracts and Aporphine Alkaloids Obtained from Annona purpurea

et al. 2020

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“…In many others [68, 71, 75–79] these effects were not registered. Some data [80] cannot be clearly interpreted. Some positive effects [57, 66] have been discussed [81] as to be the result of an infection of the cells with mycoplasms.…”

Section: Introductionmentioning

confidence: 99%

Genotoxicity Revaluation of Three Commercial Nitroheterocyclic Drugs: Nifurtimox, Benznidazole, and Metronidazole

Buschini

Ferrarini

Franzoni

et al. 2009

Journal of Parasitology Research

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Nitroheterocyclic compounds are widely used as therapeutic agents against a variety of protozoan and bacterial infections. However, the literature on these compounds, suspected of being carcinogens, is widely controversial. In this study, cytotoxic and genotoxic potential of three drugs, Nifurtimox (NFX), Benznidazole (BNZ), and Metronidazole (MTZ) was re-evaluated by different assays. Only NFX reduces survival rate in actively proliferating cells. The compounds are more active for base-pair substitution than frameshift induction in Salmonella; NFX and BNZ are more mutagenic than MTZ; they are widely dependent from nitroreduction whereas microsomal fraction S9 weakly affects the mutagenic potential. Comet assay detects BNZ- and NFX-induced DNA damage at doses in the range of therapeutically treated patient plasma concentration; BNZ seems to mainly act through ROS generation whereas a dose-dependent mechanism of DNA damaging is suggested for NFX. The lack of effects on mammalian cells for MTZ is confirmed also in MN assay whereas MN induction is observed for NFX and BNZ. The effects of MTZ, that shows comparatively low reduction potential, seem to be strictly dependent on anaerobic/hypoxic conditions. Both NFX and BNZ may not only lead to cellular damage of the infective agent but also interact with the DNA of mammalian cells.

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“…Treated Pelibuey sheep showed a significant increase in the HPRTvariant frequency (Vf) (16). The highest Vf were found in the animals with the highest steady-state MTZ in plasma.…”

Section: Introductionmentioning

confidence: 99%

“…An inverse relationship between the Vf and drug elimination was found. The fact that the animals with the lowest elimination rates of MTZ had increased gene mutations indicated that differences in pharmacokinetics constitute one potential mechanism of genotoxic susceptibility (16).…”

Section: Introductionmentioning

confidence: 99%

Environmental Toxicants in Developing Countries

Ostrosky-Wegman¹,

Gonsebatt²

1996

Environmental Health Perspectives

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Health effects from environmental toxicants may be a more serious problem in developing countries compared with developed countries because the problem is potentiated by other factors: a) the lack of or failure to enforce regulations, which allows human exposures to genotoxic agents; b) undernourishment of the lower economic and social classes that comprise the most exposed populations from industrial and agricultural activities; and c) parasitic infections that afflict a wide range of populations in both urban and rural areas. Data on the genotoxic effects of different types of exposures, including environmental exposures (natural and industrial), occupational exposures, and infections and medical treatments, are presented and discussed with the point of view that all these factors must be taken into account with respect to regulation and the protection of human health. Occupational exposures in developing countries are higher than in developed countries due to lack of stringent regulations, lack of knowledge of the risks involved, and the negligence of workers. General pollution is another important issue since developed countries have established strict regulations and risky industrial processes are being exported to developing countries, along with banned substances and dangerous industrial wastes. It should be emphasized that stringent regulations in developed countries will not prevent exposures in the long term because toxic substances that are released into the environment will ultimately reach all our future generations. -Environ Health Perspect 1 04(Suppl 3): 599-602 (1996)

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Metronidazole hprt mutation induction in sheep and the relationship with its elimination rate

Cited by 12 publications

References 27 publications

Anti-amoebic Activity of Leaf Extracts and Aporphine Alkaloids Obtained from Annona purpurea

Anti-amoebic Activity of Leaf Extracts and Aporphine Alkaloids Obtained from Annona purpurea

Genotoxicity Revaluation of Three Commercial Nitroheterocyclic Drugs: Nifurtimox, Benznidazole, and Metronidazole

Environmental Toxicants in Developing Countries

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