Micronucleus induction by metronidazole in rat vaginal mucosa

Abstract

Metronidazole (MTZ) is used for the treatment of many infectious diseases, including vaginal infections. While data indicate that MTZ is mutagenic and induces micronuclei in rodents, there is no information on the genotoxicity of MTZ in epithelial vaginal cells or cervical cells. In the present study, we have instilled MTZ into the vagina of rats and evaluated the micronucleus (MN) frequency in proestrus rat vaginal mucosal cells. The first identified proestrus before treatment was used to establish basal proestrus micronucleated cell (PMNC) frequencies. Rats then were assigned to one of five groups: a negative control, three MTZ treatment groups (30, 50, or 100 mg/kg MTZ), and a positive control treated with 2.5 mg of 5-fluorouracil (5-Fu) per rat. Following treatment for five consecutive days, vaginal cell samples were taken daily until three cycles of estrus were completed. Smears prepared from the samples were evaluated for micronuclei in proestrus cells. No differences were found between the PMNC frequencies of the negative control and the 30 and 50 mg/kg MTZ groups. The group treated with 100 mg/kg MTZ, however, had significantly elevated PMNC frequencies in the first and second proestrus samples, while 5-Fu treatment produced significant increases in PMNC frequency in the second and third proestrus. These results indicate that topical administration of relatively high concentrations of MTZ is genotoxic in rat vaginal mucosa cells.

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

“…Mutagenic activity, induced by the drug [22] as well as by the urine of therapeutically treated patients [54, 55], was found in bacterial systems. In mammalian cells, some studies [33, 34, 56–65] indicate that MTZ causes a loss of DNA helix content, strand breakage, unscheduled DNA synthesis, and SCEs, whereas others [66–72] do not confirm its genotoxicity. In some in vivo studies, MTZ was found genotoxic [73, 74].…”

Metronidazole Induced DNA Damage in Somatic Cells of Drosophila melanogaster

“…In the last 20 years MTZ has been re-evaluated regarding its potential cytotoxicity, genotoxicity, reproductive and developmental toxicity in different animal and vegetal in vivo/in vitro model systems [6][7][8][9][10][11][12][13][14][15][16].…”

Дослідження Впливу Потенційного Лікарського Засобу З Протизапальною Та Протимікробною Активністю На Структурні Зміни Слизової Оболонки Піхви На Моделі Травматичного Вагініту

“…Ібупрофен неселективно пригнічує циклооксигенезу (СОХ-1 і СОХ-2), що зменшує утворення простагландинів та тромбоксану А2 у місці запалення і тим самим зменшує розвиток запалення, інфільтрацію лейкоцитів, тромбоз судин. Ібупрофен і клотримазол добре переносяться при інтравагінальному введенні, тоді як метронідазол у високих дозах може мати негативні і побічні дії [15]. У зв'язку з цим означена комбінація досліджуваного засобу (ібупрофен, клотримазол, метронідазол) у вигляді супозиторіїв може сприяти зменшенню побічної дії при місцевому застосуванні, крім того, розробка таких засобів у формі вагінальних супозитиріїв дозволяє місцево до-…”