ABSTRACT
Dipyrone or metamizole is one of the most frequently used analgesic worldwide. Despite its widespread use, this drug may exert genotoxic and cytotoxic effects on lymphocytes. Therefore, studies with therapeutic agents that may provide protection against these effects are important. The homeopathic compound Canova® (CA) appears to be a beneficial candidate for preventing DNA damage and cellular lethality, since this compound acts as an immunomodulator associated with cytoprotective actions. Hence, the aim of the present investigation was to determine the potential cytoprotective effects of CA using cell line VERO as a model. VERO cells were incubated with sodium dipyrone and subsequently subject to the comet, apoptosis and immunocytochemistry assays. Data demonstrated that sodium dipyrone induced an increase in DNA damage index (DI) employing the comet assay. However, when VERO cells were co-treated with CA at the three concentrations studied, a significant reduction in DI was observed, indicating an antigenotoxic effect attributed to CA. Further dipyrone induced an elevation in %apoptosis at 24 and 48 hr. However, when dipyrone was co-incubated with CA, a significant reduction in %apoptosis was noted at the three concentrations of CA employed. Results from immunocytochemical analysis showed a rise in the expression of caspase 8 and cytochrome C when cells were exposed to dipyrone. In contrast, co-treatment of dipyrone and CA significantly reduced the effect of dipyrone. Therefore, evidence indicated that CA acted as an anticytotoxic and antigenotoxic agent counteracting damage induced by dipyrone.
Subject(s)
Crotalid Venoms/pharmacology , Cryoprotective Agents/pharmacology , Dipyrone/adverse effects , Materia Medica/pharmacology , Plant Extracts/pharmacology , Animals , Apoptosis , Chlorocebus aethiops , Comet Assay , Immunohistochemistry , Vero CellsABSTRACT
BACKGROUND: CANOVA(®) (CA) is a homeopathic immunomodulator. It contains several homeopathic medicines prepares according to the Brazilian Pharmacopoeia. CA is indicated in clinical conditions in which the immune system is impaired and against tumors. N-methyl-N-nitrosourea (NMU) is an N-nitroso compound, with genotoxic/mutagenic properties. Although several studies have shown promising results in the use of CA, there are no studies reporting possible antigenotoxic effects. METHOD: This study evaluated the in vitro antigenotoxic and anticytotoxic effects of CA in human lymphocytes exposed to NMU. Samples of human lymphocytes that were subjected to different concentrations of a mixture containing CA and NMU were used. The genotoxicity/antigenotoxicity of CA was evaluated by the comet assay, anticytotoxicity was assessed by quantification of apoptosis and necrosis using acridine orange/ethidium bromide. RESULTS: CA significantly reduced DNA damage induced by NMU and reduced significantly the frequency of NMU-induced apoptosis after 24 h of treatment. CONCLUSION: CA has an important cytoprotective effect significantly reducing the DNA damage and apoptosis induced by the carcinogen NMU.