title: Rapid CO breath test screening of drugs for protective effects on ribavirin-induced hemolysis in a rabbit model: a pilot study.
abstract: Hemolytic anemia is a major side effect of ribavirin antiviral treatment for chronic hepatitis C. Ribavirin dose reduction may compromise the antiviral response and erythropoietin can take several weeks to alleviate anemia. The purpose of the present study was to screen potentially protective drugs against ribavirin-induced hemolytic anemia in a rabbit model, using our modified CO breath test for measuring erythrocyte (RBC) lifespan, the gold standard diagnostic index of hemolysis. Fifteen rabbits were divided randomly into five groups (N  =  3/group): one vehicle control group, one ribavirin (only)-treated (RBV) group, and three groups initially treated with ribavirin only, followed by a combination of ribavirin with prednisone (RBV  +  Pred), polyene phosphatidyl choline (RBV  +  PPC), or reduced glutathione (RBV  +  GSH). RBC lifespan was calculated from accumulated CO measured in a closed rebreath apparatus, blood volume measured by the Evan's blue dye (EBD) dilution test, and hemoglobin concentration data. The RBC lifespan was normal in the vehicle control group (44-60 d), but reduced significantly in all of the ribavirin-treated groups before the addition of screened drugs (17-35 d). RBC lifespan rebounded significantly with the addition of glutathione, but not with the addition of prednisone or polyene phosphatidyl choline. A similar overall drug effect pattern was seen in the hemoglobin concentration and reticulocyte count data. In conclusion, the results of this pilot study indicate that reduced glutathione can attenuate ribavirin-induced hemolytic anemia, and that the RBC lifespan measured with our modified rapid CO breath test is feasible and reliable for use in animal studies.
authors: Institute of Breath Test Research, Shenzhen University, Shenzhen 518060, People's Republic of China.
authors: Yong-Jian
authors: YJ
authors: Ma
authors: Hou-De
authors: HD
authors: Zhang
authors: Chuang-Hong
authors: CH
authors: Wu
authors: Guo-Liang
authors: GL
authors: Zhu
authors: Yong-Qiang
authors: YQ
authors: Ji
authors: Jia-Liang
authors: JL
authors: Huang
authors: Li-Tao
authors: LT
authors: Du
authors: Ping
authors: P
authors: Cao
authors: De-Yue
authors: DY
authors: Zang
authors: Kun-Mei
authors: KM
authors: Ji
mesh_terms: D000743:Anemia, Hemolytic / Q000139:chemically induced*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001944:Breath Tests / Q000379:methods*; D002248:Carbon Monoxide / Q000032:analysis*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism; D008297:Male; D010865:Pilot Projects; D020011:Protective Agents / Q000494:pharmacology*; D011817:Rabbits; D012254:Ribavirin / Q000009:adverse effects*
chemical_list: D000998:Antiviral Agents; D006454:Hemoglobins; D020011:Protective Agents; D012254:Ribavirin; D002248:Carbon Monoxide; D005978:Glutathione