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The genotoxic effect of ribavirin in the patients with Crimean-Congo haemorrhagic fever

Abstract number: 1134_04_106

Tatar A., Ozkurt Z.

Objectives:  

Ribavirin (RBV) is a synthetic purine nucleoside analogue with a broad spectrum. RBV is used to therapy of viral infections because it prevents replication of a large variety of viruses. It has a lot of adverse effect such as haematologyc toxicity, mitochondrial toxicity, liver toxicity and teratogenicity. Since it has not been studied enough, the genotoxicity of RBV has not been known exactly. We aimed to seek the genotoxicity of RBV.

Methods:  

Three patients with Crimean-Congo hemorrhagic fever diagnosed clinically, laboratory and microbiologically were included in this study. The diagnosis was confirmed by ELISA. RBV was used for therapy at high dose (after 2000 mg initially dose, 1000 mg per 6 hours at first 4 days, and 500 mg per 6 hours 6 days). In these patient, we studied the mutagenic effects of RBV with 2 methods; the MN assay and the SCE method. In the 9th day of the therapy and after one month following the therapy, 2 ml perypheral blood was taken from these patients and two different blood culture for each patient carried out for 3 days. The first culture used to SCE studies and the second culture used to micronuclei studies. For SCE studies; 1ml perypheral blood and 5-BromodeoxyUridine were added to 15 ml falcon tupe including 5 ml culture medium. After 72 hours, the cultures were stopped and harvested. And then SCE method was applied. For each patient, 20 metaphase sample was examined and SCE rate was detected. For MN study, 1 ml perypheral blood was added to 15 ml falcon tupe including 5 ml culture medium. After 44 hours, cytochalasine-B was added to the cultures and then the cultures was harvested at 72nd hour. For each patient, 1000 binucleate cells were examined to establish the frequency of micronuclei. Results: The results of this study is shown as table.

Conclusion:  

We used two different methods to indicate the in vivo genotoxicity of RBV. In all patients, the SCE rates at 9th day of therapy were higher than the rates after one month following therapy. In the same way, the MN amounts increased at 9th day of therapy but they were regress to normal levels after one month. The results of this two studies were appeared the in vivo toxicity of RBV. Although the number of patient was inadequate, the presence of in vivo genotoxicity was supported by concordance between the results of MN method and of SCE method.

Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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