Vorinostat, a possible alternative to metronidazole for the treatment of amebiasis caused by Entamoeba histolytica.

AbbreviationsSAHAsuberoylanilide hydroxamic acidEhHDACHistone Deacetylase from Entamoeba histolyticaRgRadius of gyrationRMSDroot-mean-square deviationRMSFroot-mean-square fluctuationMDSmolecular dynamics simulationVMDVisual Molecular DynamicsNAMDNanoscale Molecular DynamicsPBCperiodic boundary conditionsPMEParticle Mesh Ewald3Dthree-dimensionalCαalpha carbonFDAFood and Drug AdministrationnsnanosecondsGPU CUDAGraphics Processing Unit Compute Unified Device ArchitectureCommunicated by Ramaswamy H. Sarma.

Therapeutic uses of metronidazole and its side effects: an update.

OBJECTIVE: Metronidazole is an antibiotic widely used in different medical conditions such as trichomoniasis, amoebiasis, and giardiasis among others. Its use has been associated with toxicity; however, it is not well characterized. In this review, we discuss the different therapeutic uses of metronidazole and its side effects in order to aid future investigation in this field. MATERIALS AND METHODS: Relevant information, original research articles, clinical trials, and reviews were collected from PubMed to know the state of the art of the different therapeutic uses of metronidazole and the reported side effects. RESULTS: Metronidazole was used by the first time in 1959, to treat an infection caused by Trichomonas vaginalis; subsequently, new therapeutic properties were discovered. Nowadays, Metronidazole is used to treat infections caused by Bacteroides, Fusobacteria and Clostridia, rosacea, oral and dental infections, bone and joint infections, gynecologic infections, endocarditis, septicemia, and respiratory tract infections. It also can be used to treat Crohn´s disease or even like prophylaxis, before surgical procedures. Metronidazole is well tolerated with mild to moderate side effects such as nausea, abdominal pain, and diarrhea. Nevertheless, serious neurotoxicity, optic neuropathy, peripheral neuropathy, and encephalopathy have been reported in rare cases. Their genotoxic effects observed in animal models are controversial in humans. CONCLUSIONS: The therapeutic use of metronidazole had increased worldwide. Even though it is widely used, metronidazole has been associated with neurotoxicity and genotoxicity; however, its side effects are not well established. Conversely, its veterinary use is restricted in some countries because of its tumor association. Subsequently, further studies are needed to discover the secure use of metronidazole and describe new usages for this drug.

Antimutagenicity of Stevia pilosa and Stevia eupatoria evaluated with the Ames test.

Stevia pilosa and Stevia eupatoria are plants used for various purposes in traditional medicine. In this report we studied the antimutagenic effect of methanolic extracts obtained from leaves, root, and flowers of the two species using the Ames test with and without metabolic activation. We tested the effect of the extracts on the damage induced by three mutagens with the following results: 1 - we found an inhibitory effect of both species on the mutagenicity induced by 2-aminoanthracene in the strain TA98. The best antimutagenic effect was obtained with leaves of both species and the flowers of S. eupatoria (99%), 2 - the mutations induced with N-ethyl-N'-nitro-N-nitrosoguanidine in the strain TA100 was also reduced. The flowers of S. pilosa and the root of S. eupatoria showed about 93% of inhibition, 3 - finally, the mutations induced by mitomycin-C on the strain TA102 had a reduction of 87% with the leaves of S. eupatoria. Besides, we determined the radical scavenging potential of the extracts with the DPPH method, and found a potent effect produced by all extracts, with an efficacy of more than 90%. The present study showed both antimutagenic and antioxidant potential of the tested extracts, and suggest the pertinence to confirm these effects in other models, and to accurately determine their mechanism of action.

Inhibitory effect of chlorophyllin on the frequency of micronuclei induced by sodium nitrite in mice.

In this report the potency of chlorophyllin (CHL) was evaluated to prevent two types of damage produced by nitrite in mice: the increase of micronucleated polychromatic erythrocytes (MNPE) and the bone marrow toxicity, measured as the index of polychromatic erythrocytes/normochromatic erythrocytes (PE/NE). The study was done in eight groups of male mice. The first three groups were administered orally for 4 days with sodium nitrite (10, 15 and 20 mg/kg), the daily administration with nitrite was followed by an intraperitoneal administration of CHL (4 mg/kg), three more groups were administered with the same amounts of nitrite, a seventh group of mice was treated with distilled water while another was treated with CHL (4 mg/kg). Our study produced two main results: (a) no bone marrow injury was induced by any of the tested chemicals, as indicated with the PE/NE index, and (b) CHL protected (as high as 44%) the MNPE produced in nitrite treated mice.

Inhibitory effect of chamomile essential oil on the sister chromatid exchanges induced by daunorubicin and methyl methanesulfonate in mouse bone marrow.

Different preparations of chamomile (Matricaria chamomilla) are used to treat various diseases, including inflammation and cancer; however, no studies on the plant's antigenotoxic capacity have been made. The aim of the present work was to determine the inhibitory effect of the chamomile essential oil (CO), on the sister chromatid exchanges (SCEs) produced by daunorubicin and methyl methanesulfonate (MMS) in mouse bone marrow cells. CO was analyzed and was found to contain 13 compounds, mainly bisabolol and its oxides, chamazulene, farnesene, germacrene and other sesquiterpenes. Initially, a toxic and a genotoxic analysis of CO were made; both showed negative results. To determine whether CO can inhibit the mutagenic effects induced by daunorubicin, one group of mice was administered corn oil, another group was treated with the mutagen (10 mg/kg), a third group was treated with 500 mg/kg of CO; three other groups were treated first with CO (5, 50 and 500 mg/kg) and then with 10 mg/kg of daunorubicin. In the case of MMS, the experimental groups consisted of the following: the negative control group which was administered corn oil, a group treated with 25 mg/kg of MMS, a group treated with 1000 mg/kg of CO, and three groups treated first with CO (250, 500 and 1000 mg/kg) and then with MMS (25 mg/kg). The results indicated a dose-dependent inhibitory effect on the SCEs formed by both mutagens. In the case of daunorubicin, a statistically significant result was observed in the three tested doses: from the lowest to the highest dose, the inhibitory values corresponded to 25.7, 63.1 and 75.5%. No alterations were found with respect to the cellular proliferation kinetics, but a reduction in the mitotic index was detected. As regards MMS, the inhibitory values were 24.8, 45.8 and 60.6%; no alterations were found in either the cellular proliferation kinetics or in the mitotic indices. Our results suggest that CO may be an effective antimutagen that could be considered for further study.

Induction of sister chromatid exchanges by 2,4-dichlorophenoxyacetic acid in somatic and germ cells of mice exposed in vivo.

2,4-dichlorophenoxyacetic acid (2,4-D) is one of the most widely used selective herbicides throughout the world; however, the studies that have been conducted to establish its genotoxic potential have given conflicting results. The aim of this investigation was to determine whether the herbicide increases the frequency of sister chromatid exchanges (SCEs) in bone marrow and spermatogonial cells of mice exposed in vivo. The experiment included an oral administration of 2,4-D to three groups of mice (50,100 and 200 mg/kg), as well as to a control group of animals administered with distilled water, pH 10.5 and another group injected with cyclophosphamide (50 mg/kg). In somatic cells, the results showed a significant SCE increase with the two high doses tested, a response that was manifested in a dose-dependent manner. With regard to the mitotic index and the cell proliferation kinetics, there were no modifications exerted by 2,4-D; however, cyclophosphamide induced cytotoxic damage and a cell-cycle delay. With respect to the germ cells, the genotoxic results were similar to those described earlier; that is, there was a significant SCE increase induced by the two high 2,4-D doses tested and a higher genotoxic damage was observed in the animals treated with cyclophosphamide. Our investigation established that 2,4-D is a moderate genotoxicant in mice treated in vivo with high doses, and suggests a minor hazard for humans in the present conditions of its use.