Avaliação da toxicidade aguda e do efeito cicatrizante em feridas cutâneas de um gel à base de Plectranthus neochilus, Schlechter (boldo-gambá) e Cnidoscolus quercifolius (favela) em roedores

Abstract

The objective of this work was to investigate the phytochemical characteristics and acute oral toxicity of the hydroalcoholic extracts of Plectranthus neochilus, Schlechter (boldo-opossum) and Cnidoscolus quercifolius, Pohl (favela) in Swiss mice, and the dermal toxicity and tissue repair of a formulation in Gel of the association of these plant species in Wistar rats with experimental wounds. For the phytochemical analyzes, a XEVO G2-S QTOF (Waters, Manchester, UK) mass spectrometer coupled to an Acquity UPLC liquid phase chromatograph and ESI electrospray ionization source (Waters Corp., Milford, MA, USA) . For acute oral toxicological analysis, the methodology described in Guide 423 of the OECD guidelines was used, in which nine female Swiss mice were used with three groups (n = 3 / group): Group 1 - animals treated with Plectranthus hydroalcohol extract Neochilus and Cnidoscolus quercifolius; Group 2 - treated with the extract of Cnidoscolus quercifolius and Group 3 - treated with the extract of Plectranthus neochilus. All in single dose (2000mg / kg), administered by gavage. For tissue repair and dermal toxicity 35 male Wistar rats were used. In all animals, a surgical wound of the excisional type was induced in the dorso-cervical region, which were distributed in five groups (n = 7 / group) and treated according to the respective group: Group 1 - positive control, animals treated with The commercial herbal gel; Group 2 - negative control, treated with carbopol gel 1%; Group 3 - Formulation Gel Boldo-opossum plus Favela (FGBF) 2.5%; Group 4 - FGBF 5%; Group 5 - FGBF 10%. . All received 1.0 ml of the product, topically, daily, for 14 days. It was observed that the animals showed no clinical signs of oral toxicity after exposure to the tested extracts. However, the group treated with the hydroalcoholic extract of P. neochilus at the dose studied presented a statistically significant increase in liver weight compared to the group treated with C. quercifolius or the two extracts associated. Macroscopic analysis revealed the presence of inflammation, granulation and epithelization in the wounds of all groups of rats treated topically. On the first day of treatment in the 5% or 10% FGBF groups there was a significant increase (52.53% and 53.51%) of the means and standard error of the mean of the surgical area. From the second to the sixth day of treatment in the 2.5% FGBF group there was a significant increase of 30.24%, 54.82%, 55.62%, 65.60%, 63.77%. From the fourth to the sixth day there was an increase of 71.07%, 59.65% and 94.49% in those treated with FGBF 5%. Animals treated with 10% FGBF showed a significant increase (54.32%, 94.91% and 116.70%) from the fourth to the sixth day. On the eighth day of treatment in the 2.5% group there was a significant increase of 115.30%. All the previously verified changes were compared with the positive control group. The groups treated with 2.5%, 5% or 10% FGBF presented on the 14th day the re-epithelialization process in 85.72%, 85.72% and 57.15% respectively, whereas the positive and negative control groups in 100% . The body weight of the mice treated topically with 10% FGBF had a significant reduction when compared to the other treated groups at times zero, seven, ten and thirteen days of treatment. The collagen quantification had a statistically significant reduction in the 5% and 10% FGBF groups when compared to the commercial herbal treatment. On the blood count, there was a significant increase in the platelet count in the FGBF groups, 2.5% (13.22%) and 10% FGBF (22.94%). In the biochemical analysis a statistically significant reduction in cholesterol levels was observed in the FGBF groups, 2.5% (40.02%), 5% (38.59%) and 10% (34.06%); Alkaline phosphatase had a significant increase in the FGBF groups of 2.5% (46.24%) and 5% (31.80%); In ALT and AST there was a significant increase in the 5% FGBF group (95.39% and 38.55%). All were compared to the vehicle treated group of the formulation. The histomorphological analysis of the liver of the rats presented in the 5% group mild subcapsular inflammatory infiltrate, hepatocytes with normal morphology, lipid inclusions, nuclei and evident nucleoli. It is concluded that the hydroalcoholic extracts of P. neochilus and C. quercifolius when administered in association with and / or isolated in a single dose (2000mg / kg) by gavage in Swiss mice did not cause death in any animal, classifying them as "toxicological class V "As low toxicity. The three formulations (FGBF 2.5%, 5% or 10%) when compared to the positive control, did not result in a significant improvement in the reduction of the time to the healing process of the cutaneous wounds of rats. However, among the three formulations, that of 2.5% was the one that presented increased fibroblast proliferation and more intense collagenization on the 14th day of treatment.