Svetlana A. Suhanova, Oksana V. Proskurina, E. A. Jain, A. Globenko, Madina I. Bagaeva, A. Rydlovskaya, V. Nebolsin
{"title":"新化合物XC221GI的临床前毒性分析","authors":"Svetlana A. Suhanova, Oksana V. Proskurina, E. A. Jain, A. Globenko, Madina I. Bagaeva, A. Rydlovskaya, V. Nebolsin","doi":"10.17816/eid108910","DOIUrl":null,"url":null,"abstract":"The major feature of COVID-19 is intensive virus-induced inflammation in vital body organs and spatiotemporal dysregulation of pro- and anti-inflammatory cytokines and chemokines synthesis. All this leads to unpredicted clinical progression and high risk of \"cytokine storm\" development. The \"cytokine storm\" is the pathogenetic basis for further development of life-threatening complications. Thus, there is a huge need to select effective and safe approaches that allow to control virus-induced inflammation as a part of preventive anti-inflammatory therapy. \nThis article presents toxicological characteristics of the original low-molecular compound XC221GI (1-[2-(1-methylimidazole-4-yl)-ethyl]perhydroazin-2,6-dione) from pre-clinical studies. \nThe obtained results demonstrate that the XC221GI does not have any toxic effect in repeated long-term administration. The compound was well tolerated by all animals. The no-observed-adverse-effect level (NOAEL) was 30 mg/kg per day for dogs and 450 mg/kg per day for rats. There were no effects of XC221GI on blood count, hematopoiesis and hemostasis. As well as no cytotoxic, mutagenic, genotoxic, carcinogenic properties or anaphylactogenic and immunotoxic activity were revealed for XC221GI. All known data enable to classify XC221GI as a low toxic compound and consider its safety profile as reasonably favorable.","PeriodicalId":93465,"journal":{"name":"Journal of infectious diseases and epidemiology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2022-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Toxicity profile of the new compound XC221GI from pre-clinical studies\",\"authors\":\"Svetlana A. Suhanova, Oksana V. Proskurina, E. A. Jain, A. Globenko, Madina I. Bagaeva, A. Rydlovskaya, V. Nebolsin\",\"doi\":\"10.17816/eid108910\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The major feature of COVID-19 is intensive virus-induced inflammation in vital body organs and spatiotemporal dysregulation of pro- and anti-inflammatory cytokines and chemokines synthesis. All this leads to unpredicted clinical progression and high risk of \\\"cytokine storm\\\" development. The \\\"cytokine storm\\\" is the pathogenetic basis for further development of life-threatening complications. Thus, there is a huge need to select effective and safe approaches that allow to control virus-induced inflammation as a part of preventive anti-inflammatory therapy. \\nThis article presents toxicological characteristics of the original low-molecular compound XC221GI (1-[2-(1-methylimidazole-4-yl)-ethyl]perhydroazin-2,6-dione) from pre-clinical studies. \\nThe obtained results demonstrate that the XC221GI does not have any toxic effect in repeated long-term administration. The compound was well tolerated by all animals. The no-observed-adverse-effect level (NOAEL) was 30 mg/kg per day for dogs and 450 mg/kg per day for rats. There were no effects of XC221GI on blood count, hematopoiesis and hemostasis. As well as no cytotoxic, mutagenic, genotoxic, carcinogenic properties or anaphylactogenic and immunotoxic activity were revealed for XC221GI. All known data enable to classify XC221GI as a low toxic compound and consider its safety profile as reasonably favorable.\",\"PeriodicalId\":93465,\"journal\":{\"name\":\"Journal of infectious diseases and epidemiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-08-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of infectious diseases and epidemiology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.17816/eid108910\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of infectious diseases and epidemiology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.17816/eid108910","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Toxicity profile of the new compound XC221GI from pre-clinical studies
The major feature of COVID-19 is intensive virus-induced inflammation in vital body organs and spatiotemporal dysregulation of pro- and anti-inflammatory cytokines and chemokines synthesis. All this leads to unpredicted clinical progression and high risk of "cytokine storm" development. The "cytokine storm" is the pathogenetic basis for further development of life-threatening complications. Thus, there is a huge need to select effective and safe approaches that allow to control virus-induced inflammation as a part of preventive anti-inflammatory therapy.
This article presents toxicological characteristics of the original low-molecular compound XC221GI (1-[2-(1-methylimidazole-4-yl)-ethyl]perhydroazin-2,6-dione) from pre-clinical studies.
The obtained results demonstrate that the XC221GI does not have any toxic effect in repeated long-term administration. The compound was well tolerated by all animals. The no-observed-adverse-effect level (NOAEL) was 30 mg/kg per day for dogs and 450 mg/kg per day for rats. There were no effects of XC221GI on blood count, hematopoiesis and hemostasis. As well as no cytotoxic, mutagenic, genotoxic, carcinogenic properties or anaphylactogenic and immunotoxic activity were revealed for XC221GI. All known data enable to classify XC221GI as a low toxic compound and consider its safety profile as reasonably favorable.