RESUMEN
ABSTRACT The aim of this study was to evaluate the possible protective of C. guianensis oil against MMC and CP, which are direct- and indirect-acting chemical mutagens, using the micronucleus test. Three experiments were performed. First the C. guianensis oil was co-administered to mice at doses of 250, 500 and 1000 mg/kg bw with 4 mg/kg bw MMC or 50 mg/kg bw CP. Second, the mutagenic drug (CP) was administered ip 50 mg/kg bw and after 6 and 12 hours 250 and 500 mg/kg bw of C. guianensis oil were administered. In the last, C. guianensis oil was administrated (250 and 500 mg/kg bw) during five days and after it was administered ip 50 mg/kg bw CP. The results obtained showed that the C. guianensis oil is not cytotoxic neither genotoxic to mouse bone marrow. Regarding the antimutagenic effect, all doses of C. guianensis oil were significantly (p < 0.05) effective in reducing the frequency of micronucleated polychromatic erythrocytes, when compared with MMC or CP alone. Based on these results, our results suggest that the C. guianensis oil shows medicinal potential as an antimutagenic agent, modulating the mutagenicity caused by both direct- and indirect-acting chemical mutagens, in a mammalian model.
Asunto(s)
Animales , Masculino , Ratas , Aceites de Plantas/farmacología , Células de la Médula Ósea/efectos de los fármacos , Mitomicina/antagonistas & inhibidores , Antimutagênicos/farmacología , Meliaceae , Extractos Vegetales/farmacología , Ciclofosfamida/antagonistas & inhibidores , Modelos Animales de EnfermedadRESUMEN
CMF is a combination of anticancer chemotherapeutic agents Cyclophosphamide, Methotrexate and 5-Fluorouracil. Vitamin E protects the basolateral membrane (BSM) from CMF induced lipid peroxidative damages. Rats were treated intravenously with cyclophosphamide-10 mg, methotrexate-1.0 mg and 5-fluorouracil-10 mg per kg body weight for six cycles. Vitamin E (600 mg/kg body weight) was administered orally, daily. Intestinal basolateral membrane bound ATPases (3.6.1.3), Alkalinephosphatase (3.1.1) and 5'-Nucleotidase (3.1.3.5) were protected by co-administration of vitamin E with CMF. In CMF treated rats the lipid peroxidation levels were found to be elevated with a significant depletion in membrane sulfhydryl groups. In vitamin E co-administered animals, the enzyme activities were found to be restored with concomitant reduction in malondialdehyde levels and an increase in the sulfhydryl groups. The membrane cholesterol and phospholipid levels which were altered in CMF treated rats were bought back to the normal in co-administration of vitamin E.
Asunto(s)
Animales , Protocolos de Quimioterapia Combinada Antineoplásica/antagonistas & inhibidores , Ciclofosfamida/antagonistas & inhibidores , Fluorouracilo/antagonistas & inhibidores , Mucosa Intestinal/efectos de los fármacos , Metabolismo de los Lípidos , Peróxidos Lipídicos/metabolismo , Masculino , Membranas/efectos de los fármacos , Metotrexato/antagonistas & inhibidores , Ratas , Ratas Wistar , Tirotropina/metabolismo , Vitamina E/farmacologíaRESUMEN
Cyclophosphamide induced a depletion in liver glutathione (GSH) and high rate of lipid peroxidation. GSH depletion was evident from 20 min onwards and the maximum depletion was observed at 3 hr post treatment. Lipid peroxidation was significant only after the maximum depletion of GSH. Pretreatment with either MPG or WR-77913 individually, or in combination could prevent the depletion of GSH and induction of lipid peroxidation after cyclophosphamide treatment.
Asunto(s)
Amifostina/análogos & derivados , Animales , Ciclofosfamida/antagonistas & inhibidores , Femenino , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Tiopronina/farmacologíaRESUMEN
Protein-A (PA) is a cell-surface glycoprotein of S. aureus Cowan I with immunomodulatory and anti-tumor activities, and ability to ameliorate cyclophosphamide and carbontetrachloride (CCl4) induced toxicity in rodents. The likely mechanism of this effect appears to be the anti-oxidant property of PA, evidenced in the present study by inhibition of CCl4 and Fe2-ascorbate induced lipid peroxidation in rat liver homogenates and inhibition of deaminative-oxidative degradation of L-glutamate into 2-thiobarbituric acid reactive products in a constituted chemical system. The anti-oxidant property of PA seem to arise from its molecular characteristics and the ability to interact with a superoxide derived free-radical species without any affinity for superoxide anion, hydroxyl radical and singlet oxygen species.