Toxicological and chemoprevention studies of Dalbergia ecastaphyllum (L.) Taub. stem, the botanical source of Brazilian red propolis.

OBJECTIVES: Dalbergia ecastaphyllum (L.) Taub. is a semi-prostrate species associated with estuaries, mangroves and dunes. This plant species has great ecological and economic importance, especially concerning apiculture pasture and Brazilian red propolis production. In this study, non-clinical toxicological evaluations of the hydroalcoholic extract of D. ecastaphyllum stems (DEHE), the resin production source, were conducted. In addition, the action of DEHE on genomic instability and colon carcinogenesis was investigated. METHODS AND RESULTS: The extract's chemical profile was analysed by HPLC, and medicarpin, vestitol and neovestitol were found as major compounds. DEHE showed an IC50 equivalent to 373.2 µg/ml and LC50 equal 24.4 mg/L, when evaluated using the XTT colorimetric test and the zebrafish acute toxicity assay, respectively. DEHE was neither genotoxic nor cytotoxic at the highest dose, 2000 mg/kg, by peripheral blood micronucleus test. The treatments DEHE (6 and 24 mg/kg) led to the reduction of micronuclei induced by doxorubicin (DXR) in mice. Furthermore, significantly higher serum levels of reduced glutathione were observed in animals treated with DEHE plus DXR, revealing an antioxidant effect. Treatments with DEHE (48 mg/kg) led to a significant reduction in pre-neoplastic lesions induced by the 1,2-dimethylhydrazine (DMH) carcinogen in the rat colon. Immunohistochemical analysis revealed significantly lower levels of expression of COX-2 (86%) and PCNA (83%) in the colon of rats treated with DEHE plus DMH, concerning those treated with the carcinogen. CONCLUSIONS: These results indicate the involvement of anti-inflammatory and antiproliferative pathways in the protective effect of DEHE.

Evaluation of the antiseptic and wound healing potential of polyhexamethylene guanidine hydrochloride as well as its toxic effects.

The synthetic polyhexamethylene guanidine hydrochloride (PHMGH) polymer presents antifungal and antimicrobial activities in vitro. However, in vivo reports regarding its antiseptic and healing activity are scarce in the scientific literature. Thus, the present study aimed to evaluate the antimicrobial and healing effects, as well as toxicological parameters, of a topical solution containing 0.5% PHMGH (Akwaton®) in the treatment of superficial skin wounds experimentally induced on the dorsum of rodents. In addition, non-clinical safety studies were also conducted for use in human health, such as acute oral toxicity and genotoxicity tests. Animals did clinically not present dermatitis. After two days of topical treatment, PHMGH showed a significant antiseptic effect compared to the untreated group, reducing the number of colony-forming units by 72%, reaching 100% on the fourth day of treatment. The animals treated with PHMGH showed a significant area reduction of the skin lesions in relation to the untreated group, indicating a healing effect of the polymer. Moreover, PHMGH treatment led to a significant increase in fibroblasts when compared to the untreated group, revealing its healing action. No significant differences were observed between the biochemical indicators of hepatoxicity and nephrotoxicity, nor genotoxicity between the PHMGH-treated and the negative control groups. The results of acute oral toxicity showed that PHMGH at 5% presents a lethal dose 50% greater than the 2000 mg/kg. At a concentration of 5%, PHMGH did not show genotoxicity nor cytotoxicity at doses up to 1500 mg/kg through the micronucleus assay in mice. Therefore, 0.5% PHMGH showed an antimicrobial and healing effect, with no toxicity, and could be a promising adjunct in the microbial control of healing wounds.

Betulinic acid modulates urethane-induced genotoxicity and mutagenicity in mice and Drosophila melanogaster.

Betulinic acid (BA) is a pentacyclic triterpenoid found in several plant species. Urethane (URE) is a known promutagen. Here, we examine the genotoxicity and mutagenicity of BA alone or in combination with URE using the bone marrow micronucleus assay in mice bone marrow cells and the Somatic Mutation and Recombination Test in Drosophila melanogaster. Findings revealed that BA alone was not genotoxic, but reduced the frequency of micronucleus when compared to the positive control. No significant differences were observed in the cytotoxicity. Biochemical analyzes showed no significant differences for liver (AST and ALT) or renal (creatinine and urea) function parameters, indicating the absence of hepatotoxic and nephrotoxic effects. BA alone did not increase the frequency of mutant spots, but reduced the total frequency of mutant spots when co-administered with URE in both ST and HB crosses. In addition, BA reduced the recombinogenic effect of URE at the highest concentrations of both crosses. In conclusion, under experimental conditions, BA has modulatory effects on the genotoxicity induced by URE in mice, as well as in somatic cells of D. melanogaster. We suggest that the modulatory effects of BA may be mainly due to its antioxidant and apoptotic properties.