title: Side-Effects of Irinotecan (CPT-11), the Clinically Used Drug for Colon Cancer Therapy, Are Eliminated in Experimental Animals Treated with Latex Proteins from Calotropis procera (Apocynaceae).
abstract: Intestinal mucositis (IM) is the critical side effect of irinotecan (CPT-11), which is the front-line drug used for the treatment of colorectal cancer. This study aimed to evaluate the effectiveness of latex proteins (LP) from Calotropis procera to prevent IM and diarrhea in animals. Swiss mice were treated daily with saline or LP (1, 5, or 50 mg/kg, i.v.) 24 h prior to CTP-11 (75 mg/kg/4 days, i.p) and for additional 6 days. Animal survival, body weight variation, and diarrhea were registered. After animal sacrifice (day 7 post first injection of CPT-11), intestinal samples were collected to study morphology and inflammatory parameters. Animals given LP exhibited improved parameters (survival, body weight, and absence of diarrhea) as compared with the CPT-11 control. The severity of IM observed in animals given CPT-11 was reduced in animals treated with LP. Treatment with LP also prevented the reduction in the villus/crypt ratio promoted by CPT-11. The rise in MPO activity and pro-inflammatory cytokines, over-contractility of the smooth muscle, and diarrhea were all abrogated in LP-treated mice. Markedly reduced immunostaining intensity for COX-2, TNF-α, IL-1β, iNOS, and NF-κB was observed in the intestinal tissue of animals treated with LP. The side-effects of CPT-11 were eliminated by LP treatment in experimental animals and improved clinical parameters characteristic of IM All known biochemical pathogenesis. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Departamento de Fisiologia e Farmacologia/UFC, Coronel Nunes de Melo, 1127 Rodolfo Teófilo, 60430-270, Ceará, Brazil.
authors.forename: Nylane Maria Nunes
authors.initials: NM
authors.lastname: de Alencar
authors.affiliation: Departamento de Fisiologia e Farmacologia/UFC, Coronel Nunes de Melo, 1127 Rodolfo Teófilo, 60430-270, Ceará, Brazil.
authors.forename: Flávio
authors.initials: F
authors.lastname: da Silveira Bitencourt
authors.affiliation: Departamento de Fisiologia e Farmacologia/UFC, Coronel Nunes de Melo, 1127 Rodolfo Teófilo, 60430-270, Ceará, Brazil.
authors.forename: Ingrid Samantha Tavares
authors.initials: IS
authors.lastname: de Figueiredo
authors.affiliation: Departamento de Fisiologia e Farmacologia/UFC, Coronel Nunes de Melo, 1127 Rodolfo Teófilo, 60430-270, Ceará, Brazil.
authors.forename: Patrícia Bastos
authors.initials: PB
authors.lastname: Luz
authors.affiliation: Departamento de Fisiologia e Farmacologia/UFC, Coronel Nunes de Melo, 1127 Rodolfo Teófilo, 60430-270, Ceará, Brazil.
authors.forename: Roberto César P
authors.initials: RC
authors.lastname: Lima-Júnior
authors.affiliation: Departamento de Fisiologia e Farmacologia/UFC, Coronel Nunes de Melo, 1127 Rodolfo Teófilo, 60430-270, Ceará, Brazil.
authors.forename: Karoline Sabóia
authors.initials: KS
authors.lastname: Aragão
authors.affiliation: Departamento de Fisiologia e Farmacologia/UFC, Coronel Nunes de Melo, 1127 Rodolfo Teófilo, 60430-270, Ceará, Brazil.
authors.forename: Pedro Jorge Caldas
authors.initials: PJ
authors.lastname: Magalhães
authors.affiliation: Departamento de Morfologia/UFC, Delmiro de Farias S/N, Rodolfo Teófilo, 60416030, Ceará, Brazil.
authors.forename: Gerly Anne
authors.initials: GA
authors.lastname: de Castro Brito
authors.affiliation: Departamento de Fisiologia e Farmacologia/UFC, Coronel Nunes de Melo, 1127 Rodolfo Teófilo, 60430-270, Ceará, Brazil.
authors.forename: Ronaldo Albuquerque
authors.initials: RA
authors.lastname: Ribeiro
authors.affiliation: Departamento de Fisiologia e Farmacologia/UFC, Coronel Nunes de Melo, 1127 Rodolfo Teófilo, 60430-270, Ceará, Brazil.
authors.forename: Ana Paula Fragoso
authors.initials: AP
authors.lastname: de Freitas
authors.affiliation: Departamento de Bioquímica e Biologia Molecular/UFC, Campus do Pici, Caixa Postal 6033, 60451-970, Ceará, Brazil.
authors.forename: Marcio Viana
authors.initials: MV
authors.lastname: Ramos
mesh_terms: D000818:Animals; D029062:Apocynaceae / Q000737:chemistry*; D031107:Calotropis / Q000737:chemistry*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D000077146:Irinotecan; D007840:Latex / Q000494:pharmacology*; D008297:Male; D051379:Mice
chemical_list: D007840:Latex; D000077146:Irinotecan; D002166:Camptothecin
keywords: Calotropis procera; cytokines; irinotecan; latex proteins; mucositis