ABSTRACT
Considering the promising previous results of ct-[RuCl(CO)(dppb)(bipy)]PF6 (where dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2,2'-bipyridine) as an antitumor agent, novel biological assays evaluating its toxicogenic potential were performed. The genotoxicity of the compound was evaluated by the in vitro micronucleus test (V79, Chinese hamster lung fibroblasts; HepG2, hepatocellular carcinoma cells), in vivo bone marrow micronucleus test and comet assay in hepatocytes (Swiss mice). The animals were treated with 0.63, 1.25, 2.5 and 5.0 mg/kg body weight (bw) of the compound. Negative (water) and positive (cisplatin, 1.5 mg/kg bw; methyl methanesulfonate, 40 mg/kg bw) controls were included. The parameters considered in the comet assay were the percentage of tail DNA, tail moment and tail length. The results of the in vitro micronucleus tests showed the absence of genotoxicity in V79 cells, while the compound was genotoxic in HepG2 cells at a concentration of 1.25 µm. In the in vivo micronucleus test, the compound was not genotoxic at the different doses evaluated. In the comet assay, only the dose of 5.0 mg/kg bw resulted in a significant increase in the frequency of DNA damage in hepatocytes when compared to the negative control. The genotoxic effect observed in HepG2 cells and in the liver comet assay indicates that the compound was metabolized by hepatic cells.
Subject(s)
Antineoplastic Agents/pharmacology , Cell Proliferation/drug effects , Coordination Complexes/pharmacology , DNA Damage , Micronuclei, Chromosome-Defective/chemically induced , Ruthenium/chemistry , 2,2'-Dipyridyl/chemistry , Animals , Antineoplastic Agents/toxicity , Cell Survival/drug effects , Coordination Complexes/chemistry , Coordination Complexes/toxicity , Cricetulus , Dose-Response Relationship, Drug , Erythrocytes/drug effects , Erythrocytes/pathology , Fibroblasts/drug effects , Fibroblasts/pathology , Hep G2 Cells , Hepatocytes/drug effects , Hepatocytes/pathology , Humans , Male , Mice , Phosphines/chemistryABSTRACT
Copaiba oleoresins are used in alternative medicine as anti-inflammatory, antitumoral, and antimicrobial treatments. (-)-Copalic acid (CA) is the major diterpene found in exudates from Copaifera species. We have examined the genotoxicity and the chemopreventive potential of Copaifera multijuga oleoresin (CM) and CA. Genotoxicity assessment was examined with the peripheral blood micronucleus test and the comet assay (male Swiss mouse hepatocytes). In the chemoprevention study, we evaluated the effects of CM and CA on the formation of 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in male Wistar rat colon. Neither agent caused a significant increase in micronucleus frequency relative to controls, but the highest CM dose tested (400mg/kg b.w.) caused DNA damage in the comet assay. Both agents significantly reduced the frequency of DMH-induced ACF. Both CM and CA suppressed ACF formation and may have a protective effect against colon carcinogenesis.
Subject(s)
Anticarcinogenic Agents/pharmacology , DNA Damage , Diterpenes/pharmacology , Fabaceae/chemistry , Micronuclei, Chromosome-Defective/chemically induced , Plant Extracts/pharmacology , Aberrant Crypt Foci/prevention & control , Animals , Anticarcinogenic Agents/isolation & purification , Anticarcinogenic Agents/toxicity , Colonic Neoplasms/prevention & control , Comet Assay , Diterpenes/isolation & purification , Diterpenes/toxicity , Dose-Response Relationship, Drug , Hepatocytes/drug effects , Hepatocytes/pathology , Male , Mice , Plant Extracts/isolation & purification , Plant Extracts/toxicity , Rats, WistarABSTRACT
The chemical composition and the in vitro schistosomicidal effects of the essential oil of Plectranthus neochilus (PN-EO) grown in Southeast Brazil was studied. ß-Caryophyllene (1; 28.23%), α-thujene (2; 12.22%), α-pinene (3; 12.63%), ß-pinene (4; 6.19%), germacrene D (5; 5.36%), and caryophyllene oxide (6; 5.37%) were the major essential oil constituents. This chemical composition differed from that previously reported for specimens harvested in Africa. Concerning the in vitro schistosomicidal activity against adult Schistosoma mansoni worms, PN-EO was considered to be active, but less effective than the positive control praziquantel (PZQ) in terms of separation of coupled pairs, mortality, decrease in the motor activity, and tegumental alterations. However, PN-EO caused an interesting dose-dependent reduction in the number and the percentage of developed S. mansoni eggs. These results suggest that PN-EO might be very promising for the development of new schistosomicidal agents.