Cytotoxicity of trans-Dehydrocrotonin from Croton cajucara on V79 Cells and Rat Hepatocytes

Abstract

The cytotoxicity of trans-dehydrocrotonin (DHC), an antiulcerogenic diterpene from Croton cajucara (Euphorbiaceae), was assessed on a V79 fibroblast cell line and on rat hepatocytes. Three independent endpoints for cytotoxicity were evaluated: DNA content, MTT reduction and neutral red uptake (NRU). For the V79 cells IC50 values of 253 and 360 microM were obtained for the NRU and MTT tests. The cytotoxic effect of DHC was time exposure dependent and no ability to recover after treatment was observed. For the rat hepatocytes IC50 values of 8, 300 and 400 microM for the MTT, DNA and NRU assays were obtained. The greater toxicity observed for the MTT test was inhibited when the experiment was performed using non-fresh hepatocytes in an age-dependent fashion. The treatment of V79 cells with the conditioned medium resulting after hepatocyte incubation with DHC showed an enhancement of MTT reduction without any evident toxic effects on fibroblasts. These results suggest that DHC has basal cytotoxic effects as observed on V79 fibroblasts and expresses a selective cytotoxicity after its metabolization by the hepatocytes. The bioactivation of DHC is mediated by cytochrome P450 and could generate metabolites that have no toxicity for V79 fibroblasts.

Potential benefits of the 19-nor-clerodane trans-dehydrocrotonin on the central nervous system

“…According to Maciel et al (2000) ethnobotanical investigations, this Croton may not produce hepatotoxicity if used as a tea preparation to be taken at a dose of a cup twice a day during 2 to 4 weeks. It has been supported by Rodríguez & Haun (1999) who found on in vitro experiments that DCTN showed only hepatic damage after administered in subchronic treatment.…”

Diterpenylquinone Hybrids: Synthesis and Assessment of Gastroprotective Mechanisms of Action in Human Cells

“…* p < 0.05 compared to NaT group. The results showed significant cytoprotective effect (p < 0.05) for the starting quinones 1 (25,22 and 29% cell protection at 285, 143 and 71 µM, respectively) and 2 (27,23 and 23%, at 146, 73 and 37 µM respectively), the diterpenes 5 (35, 25 and 19% reduction in cell viability at 333, 167 and 83 µM, respectively) and 6 (25% cell viability reduction at 71 and 35 µM) ( Figure 5). …”

Uma revisão das atividades biológicas da trans-desidrocrotonina, um produto natural obtido de Croton cajucara

“…A atividade citotóxica da DCTN foi estudada em diversas células tumorais das seguintes linhagens: células fi broblásticas pulmonares de hamsters chineses (Souza-Brito et al, 1998;Grynberg et al, 1999;Melo et al, 2001;Rodriguez;Haun, 1999;Freire et al, 2003), células promielocíticas leucêmicas (HL60) (Anazetti et al, 2003;Anazetti et al, 2004;Corrêa et al, 2005), hepatócitos de ratos (Rodriguez; Haun, 1999; Corrêa et al, 2005) (Maciel et al, 2002a;Grynberg et al, 1999;Melo et al, 2004).…”

“…O estudo em células promielocíticas leucêmicas (HL60) e células mononucleares sanguíneas humanas, mostrou diferenciação celular e indução de apoptose em células do tipo HL60 e baixa toxicidade nas células sanguíneas (Anazetti et al, 2003;Anazetti et al, 2004). A citotoxicidade da DCTN (8 μM), analisada em hepatócitos extraído de ratos, comprovou pelos danos causados nas células hepáticas após tratamento subcrônico da DCTN, a ocorrência de toxicidade seletiva (Rodriguez; Haun, 1999). Outro estudo mostrou a infl uência da DCTN na inibição de fosfatase em células HL60, induzindo apoptose (Corrêa et al, 2005).…”