Evaluation of Ribavirin Genotoxicity with Sister Chromatid Exchange and Micronuclei Assays in Humans (original) (raw)
Related papers
Genotoxic effect of ribavirin in patients with Crimean-Congo hemorrhagic fever
Japanese journal of infectious diseases, 2005
In this study, we investigated the in vivo genotoxicity of ribavirin in humans, studying 3 patients with Crimean-Congo hemorrhagic fever who were treated with high-dose ribavirin. In order to evaluate genotoxicity, both the micronucleus (MN) test and the sister chromatid exchange (SCE) test were used. In all patients, blood samples were taken during and after therapy. Whole blood cultures were performed for 72 h and the MN assay and SCE test were then carried out to demonstrate the genotoxicity. In all patients, both SCE and MN amounts were found to be higher in the samples which were taken during therapy than in those at 1 month after therapy. The results of our study reveal that ribavirin has a reversible in vivo genotoxic effect on humans.
The genotoxic and cytotoxic effects of ribavirin in rat bone marrow
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2002
The genotoxic and cytotoxic effects of the antiviral drug, ribavirin, was studied in rat bone marrow by employing the micronucleus assay. Ribavirin in doses of 10, 15, 20, 30, 50, 75, 100 and 200 mg/kg, and cyclophosphamide (CP) 40 mg/kg (only for sex-difference study) were injected intraperitoneally. Bone marrow was collected at 24 h and 48 h following the injection. To evaluate the recovery, the bone marrow was also sampled at 72 h from 20, 100 and 200 mg/kg treated rats. The micronucleus assay was conducted according to the standard procedure. Ribavirin elevated the incidence of micronuclei (except 10 mg/kg) in erythrocytes (P < 0.01). The micronucleated polychromatic erythrocytes showed the initial steep increase at 15 and 20 mg/kg dose level, then with the gradual increase, possibly due to the limited metabolism and action of higher doses. The incidence of micronucleated normochromatic erythrocytes was not dose dependent. The effect was more at 48 h than 24 h due to prolonged toxicity of the drug or its metabolites, and by 72 h, recovery was observed eventhough the genotoxicity was significant. The PCE% decreased as the dose was increased up to 75 mg/kg, then without much difference between two higher doses. Only 100 mg/kg ribavirin and CP showed more toxicity on male rats. Cytotoxicity was seen due to hindered erythropoiesis or cell destruction. Our findings suggest that ribavirin is genotoxic and cytotoxic agent for rat bone marrow.
The Journal of infectious diseases, 2018
The use of ribavirin to treat Crimean-Congo hemorrhagic fever virus (CCHFV) infection has been controversial, based on uncertainties about its antiviral efficacy in clinical case studies. We studied the effect of ribavirin treatment on viral populations in a recent case by deep-sequencing analysis of plasma samples obtained from a CCHFV-infected patient before, during, and after a 5-day regimen of ribavirin treatment. The CCHFV load dropped during ribavirin treatment, and subclonal diversity (transitions) and indels increased in viral genomes during treatment. Although the results are based on a single case, these data demonstrate the mutagenic effect of ribavirin on CCHFV in vivo.
TURKISH JOURNAL OF MEDICAL SCIENCES, 2016
/treatment/ index.html). Ribavirin, which is used for the treatment of viral hemorrhagic fever syndromes, was shown to inhibit the growth of CCHF virus in animal models and in vitro (6,7). Many observational and case-control studies were reported in Turkey, Iran, and Pakistan in which oral and intravenous ribavirin was used for treatment (8,9-20). Recently, two systemic reviews and meta-analyses were published evaluating the efficacy of ribavirin (21,22). Yet, whether ribavirin is effective has not been clarified. The aim of the present study was to evaluate the effects of oral Background/aim: In this observational study, the effects of oral ribavirin on clinical and laboratory parameters and blood products use in patients with Crimean-Congo hemorrhagic fever (CCHF) were evaluated. Materials and methods: CCHF patients (n = 100) who were hospitalized between 2007 and 2010 were included. Oral ribavirin was administered to 56 patients with symptom duration less than 5 days. Forty-four patients did not receive ribavirin (control group). The patients that received ribavirin in the first 3 days following the initiation of symptoms were designated as Group 1 (n = 29) and the others were designated as Group 2. Results: Ribavirin-treated and untreated groups were similar in terms of demographic and most clinical characteristics. Leukocyte and platelet counts were lower in the ribavirin group than in the control group, but values of prothrombin time, activated partial thromboplastin time, aspartate aminotransferase, creatinine phosphokinase, and lactate dehydrogenase were higher (P
The Efficacy of Oral Ribavirin in the Treatment of Crimean‐Congo Hemorrhagic Fever in Iran
Clinical Infectious Diseases, 2003
We compared the mortality rate among patients suspected of having Crimean-Congo hemorrhagic fever (CCHF) who received treatment with oral ribavirin and those who did not. Ninety-seven (69.8%) of 139 treated patients suspected of having CCHF survived, and 61 (88.9%) of 69 treated patients with confirmed CCHF survived. The efficacy of oral ribavirin was 80% among patients with confirmed CCHF and 34% among patients suspected of having CCHF. Considering the limitations of observational studies, we conclude that oral ribavirin is an effective treatment for the hemorrhagic form of CCHF.
Journal of Clinical Virology, 2010
Background: The efficiency of ribavirin for treatment of Crimean-Congo hemorrhagic fever (CCHF) is unknown. In the literature, prospective randomized studies investigating the efficacy of ribavirin are not found. Objectives: To investigate the efficacy of ribavirin in treatment of patients with CCHF. Study design: In this prospective randomized cohort study 136 cases were included between June 2004 and August 2007. The diagnosis was confirmed in the CCHF reference laboratory of Refik Saydam National Hygiene Central Institute of the Turkish Ministry of Health. Patients either received ribavirin plus supportive treatment (Group A) (n = 64) or only supportive treatment (Group B) (n = 72). For the evaluation of efficacy of ribavirin, various parameters were compared between Group A and Group B. Results: As well as the similarity of demographic features between the two groups, there were no statistical differences in incubation time; hospitalization time; patients requiring platelet replacement therapy; the time taken for platelet levels to return to normal levels and mortality. In Group B, the rate of tick contact was higher (p = 0.03). In Group A, leukocyte levels took longer to return to the normal levels (p = 0.02). Conclusion: In our study, there was no positive effect determined on clinical or laboratory parameters in CCHF patients treated with ribavirin, also it was observed that leukocyte levels took longer to return to normal (p = 0.02) and, while not statistically significant, the longer period of hospitalization (p = 0.09) needed was observed as a negative effect. Because of these reasons, it is thought that the use of ribavirin makes no significant contribution to the prognosis of the CCHF disease.
International Journal of Infectious Diseases, 2013
Crimean-Congo hemorrhagic fever Ribavirin S U M M A R Y Crimean-Congo hemorrhagic fever (CCHF) is a viral infection associated with a high mortality rate. Ribavirin is the only drug used in the treatment of this disease. Studies investigating the effectiveness of ribavirin in CCHF have been retrospective and to date have included only a small number of cases. In recent years, due to climate changes, the number of cases of CCHF in Turkey has increased, and experience in the treatment of CCHF has improved. Several studies have evaluated the efficacy of ribavirin in Turkey, including one randomized controlled trial and two studies with a large number of cases. In these studies, ribavirin therapy was not shown to decrease mortality rates; the mortality rate was 2-9% in patients treated with ribavirin and 5.6-11% in those who were not treated with this drug. These findings suggest that patients with CCHF should be followed with supportive care only until randomized controlled trials with larger groups have been conducted. ß