Márcio V Ramos1, Ana Paula F Freitas2, Renata F C Leitão3, Deiziane V S Costa3, Gilberto S Cerqueira3, Nylane M N Alencar4, Larissa Barbosa N Freitas5, Gerly Anne C Brito6, Dainesy S Martins4, Conceição S Martins3. 1. Departamento de Bioquímica e Biologia Molecular, Centro de Ciências, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil. vramos@ufc.br. 2. Universidade da Integração Internacional da Lusofonia Afro-Brasileira (UNILAB), Redenção, Ceará, Brazil. 3. Departamento de Morfologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil. 4. Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil. 5. Departamento de Bioquímica e Biologia Molecular, Centro de Ciências, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil. 6. Departamento de Morfologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil. gerlybrito@hotmail.com.
Abstract
OBJECTIVE AND DESIGN: Oral mucositis (OM) is an intense inflammatory reaction progressing to tissue damage and ulceration. The medicinal uses of Calotropis procera are supported by anti-inflammatory capacity. PII-IAA, a highly homogenous cocktail of laticifer proteins (LP) prepared from the latex of C. procera, with recognized pharmacological properties was tested to treat OM. MATERIALS AND SUBJECTS: Male Golden Sirius hamsters were used in all treatments. TREATMENT: The latex protein samples were injected i.p. (5 mg/Kg) 24 h before mucositis induction (mechanical trauma) and 24 h later. METHODS: Histology, cytokine measurements [ELISA], and macroscopic evaluation [scores] were performed. RESULTS: PII-IAA eliminated OM, accompanied by total disappearance of myeloperoxidase activity and release of IL-1b, as well as reduced TNF-a. Oxidative stress was relieved by PII-IAA treatment, as revealed by MDA and GSH measurements. PII-IAA also reduced the expression of adhesion molecules (ICAM-1) and Iba-1, two important markers of inflammation, indicating modulatory effects. Histological analyses of the cheek epithelium revealed greater deposition of type I collagen fibers in animals given PII-IAA compared with the control group. This performance was only reached when LPPII was treated with iodoacetamide (IAA), an irreversible inhibitor of proteolytic activity of cysteine proteases. The endogenous proteolytic activity of LPPII induced adverse effects in animals. Candidate proteins involved in the phytomodulatory activity are proposed. CONCLUSIONS: Therapy was successful in treating OM with the laticifer protein fraction, containing peptidases and osmotin, from Calotropis procera. The effective candidate from the latex proteins for therapeutic use is PII-IAA.
OBJECTIVE AND DESIGN: Oral mucositis (OM) is an intense inflammatory reaction progressing to tissue damage and ulceration. The medicinal uses of Calotropis procera are supported by anti-inflammatory capacity. PII-IAA, a highly homogenous cocktail of laticifer proteins (LP) prepared from the latex of C. procera, with recognized pharmacological properties was tested to treat OM. MATERIALS AND SUBJECTS: Male Golden Sirius hamsters were used in all treatments. TREATMENT: The latex protein samples were injected i.p. (5 mg/Kg) 24 h before mucositis induction (mechanical trauma) and 24 h later. METHODS: Histology, cytokine measurements [ELISA], and macroscopic evaluation [scores] were performed. RESULTS: PII-IAA eliminated OM, accompanied by total disappearance of myeloperoxidase activity and release of IL-1b, as well as reduced TNF-a. Oxidative stress was relieved by PII-IAA treatment, as revealed by MDA and GSH measurements. PII-IAA also reduced the expression of adhesion molecules (ICAM-1) and Iba-1, two important markers of inflammation, indicating modulatory effects. Histological analyses of the cheek epithelium revealed greater deposition of type I collagen fibers in animals given PII-IAA compared with the control group. This performance was only reached when LPPII was treated with iodoacetamide (IAA), an irreversible inhibitor of proteolytic activity of cysteine proteases. The endogenous proteolytic activity of LPPII induced adverse effects in animals. Candidate proteins involved in the phytomodulatory activity are proposed. CONCLUSIONS: Therapy was successful in treating OM with the laticifer protein fraction, containing peptidases and osmotin, from Calotropis procera. The effective candidate from the latex proteins for therapeutic use is PII-IAA.
Authors: Nylane Maria Nunes de Alencar; Flávio da Silveira Bitencourt; Ingrid Samantha Tavares de Figueiredo; Patrícia Bastos Luz; Roberto César P Lima-Júnior; Karoline Sabóia Aragão; Pedro Jorge Caldas Magalhães; Gerly Anne de Castro Brito; Ronaldo Albuquerque Ribeiro; Ana Paula Fragoso de Freitas; Marcio Viana Ramos Journal: Phytother Res Date: 2016-12-02 Impact factor: 5.878