title: Preclinical safety evaluation of IQG-607 in rats: Acute and repeated dose toxicity studies.
abstract: In the present study, we evaluated the safety and the possible toxic effects of IQG-607 after acute and 90-day repeated administrations in rats. Single oral administration of IQG-607 (300 or 2000 mg/kg) on female rats did not result in any mortality. No gross lesions were observed in the animals at necropsy. Ninety-day administration test resulted in 20% of deaths, in both male and female rats administered with the highest dose of IQG-607, 300 mg/kg. Repeated administration of the IQG 607 (25, 100 and 300 mg/kg) did not result in any significant body mass alteration, or changes in food and water consumption. The most important clinical sign observed was salivation in both sexes. Importantly, long-term treatment with IQG-607 did not induce alterations in any hematological (for both sex) and serum biochemical (for female) parameters evaluated, even at the highest dose tested. Treatment of male rats with 100 or 300 mg/kg of IQG-607 decreased total cholesterol levels, while animals treated with 100 mg/kg also presented reduction on triglyceride levels. Of note, no treatment induced significant histopathological alterations in tissues of all organs and glands analyzed, even in that group that received the highest dose of IQG-607.
authors.affiliation: Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga 6681, Prédio 92A Tecnopuc, 90619-900, Porto Alegre, Brazil; Programa de Pós-Graduação em Medicina e Ciências da Saúde, PUCRS, Porto Alegre, Brazil.
authors.forename: Valnês S
authors.initials: VS
authors.lastname: Rodrigues-Junior
authors.affiliation: Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga 6681, Prédio 92A Tecnopuc, 90619-900, Porto Alegre, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular, PUCRS, Porto Alegre, Brazil.
authors.forename: Pablo
authors.initials: P
authors.lastname: Machado
authors.affiliation: Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
authors.affiliation: Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors.forename: Jarbas M
authors.initials: JM
authors.lastname: Siqueira
authors.affiliation: Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors.forename: Edinéia L
authors.initials: EL
authors.lastname: Andrade
authors.affiliation: Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors.forename: Allisson F
authors.initials: AF
authors.lastname: Bento
authors.affiliation: Programa de Pós-Graduação em Medicina e Ciências da Saúde, PUCRS, Porto Alegre, Brazil; Instituto de Toxicologia e Farmacologia, PUCRS, Porto Alegre, Brazil.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Campos
authors.affiliation: Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga 6681, Prédio 92A Tecnopuc, 90619-900, Porto Alegre, Brazil; Programa de Pós-Graduação em Medicina e Ciências da Saúde, PUCRS, Porto Alegre, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular, PUCRS, Porto Alegre, Brazil.
authors.forename: Luiz A
authors.initials: LA
authors.lastname: Basso
authors.affiliation: Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga 6681, Prédio 92A Tecnopuc, 90619-900, Porto Alegre, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular, PUCRS, Porto Alegre, Brazil. Electronic address: diogenes@pucrs.br.
authors.forename: Diógenes S
authors.initials: DS
authors.lastname: Santos
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015992:Body Mass Index; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000633:toxicity*; D007538:Isoniazid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D051381:Rats; D012472:Salivation / Q000187:drug effects; D023382:Toxicity Tests, Acute / Q000379:methods
chemical_list: D005296:Ferrous Compounds; C576457:pentacyano(isoniazid)ferrate(II); D007538:Isoniazid
keywords: Drug development; IQG-607; Preclinical toxicology; Rodents; Tuberculosis