RESUMO
The first analysis of water pollutants using biomarkers at the Guarapiranga Reservoir, which supplies water for one-third of the population of the São Paulo megalopolis (Brazil), is reported. Studies were performed before and after the start of water pumping to the Guarapiranga from the highly polluted Billings reservoir. Billings's water was purified by passing through the natural wetland located near Guarapiranga. Liver enzymes of Oreochromis niloticus (tilopias) obtained from both reservoirs served as biomarkers of pollution in a comparison with animals obtained from a reference site. Enhanced levels of total cytochromes P450 (3.4 times) and b5 (2.7 times) and activity of cytochrome c (P450) reductase (2.2 times) were observed in specimens collected near the water influx from the Billings before the pumping started. However, these parameters were significantly decreased 3 months later. This effect is probably due to dilution of pollutants because of the increased level of water in the Guarapiranga.
Assuntos
Ciclídeos/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Monitoramento Ambiental , Microssomos Hepáticos/enzimologia , Poluentes Químicos da Água/análise , Animais , Benzo(a)pireno/análise , Brasil , Cidades , Sistema Enzimático do Citocromo P-450/análise , Citocromos b5/análise , Citocromos b5/metabolismo , Indução Enzimática , Resíduos Industriais , Fenantrenos/análise , Bifenilos Policlorados/análise , Esgotos , Gerenciamento de Resíduos , Abastecimento de ÁguaRESUMO
The cytotoxicity of two nitroheterocyclic compounds (NHCD), Nitracrine, 1-nitro-9(3-3-dimethylaminopropylamino) acridine and Quinifuryl, 2-(5'-nitro-2'-furanyl) ethenyl-4-[N-[4-(N,N-diethylamino)-1'-methylbutyl] carbamoyl] quinoline, towards two lines of leukaemic cells and a line of non-transformed cells, was measured in comparison, on the dark and under illumination with visible light (350-450 nm). Both drugs showed highly elevated cytotoxicity when illuminated with LC(50) values 7-35 times lower after 1 h illumination compared to 1 h incubation of cells incubation with drug on the dark. Cytotoxicity of Nitracrine toward all cell lines studied exceeded that of Quinifuryl, both on the dark and under illumination, so that approximately 10 times lower concentration of former drug was needed to reach the same toxicity as the latter. General toxic effect was calculated as a direct cell kill and a cell proliferation arrest. The effect >80% for both drugs was achieved after 1 h cell illumination with as low drug concentrations as 0.2 microM for Quinifuryl and 0.02 microM for Nitracrine.
Assuntos
Antineoplásicos/farmacologia , Luz , Nitracrina/farmacologia , Quinolinas/farmacologia , Animais , Antineoplásicos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Escuridão , Avaliação Pré-Clínica de Medicamentos , Humanos , Células K562 , Leucemia P388 , Camundongos , Células NIH 3T3 , Nitracrina/toxicidade , Quinolinas/toxicidadeRESUMO
We performed a comparative analysis of cytochrome P450, cytochrome b5, MFO associated enzymes and cytosolic antioxidant enzymes in hepatic microsomes and cytosolic fractions prepared from five animal species representing three vertebrate classes living in tropical conditions (Brazil). The data obtained show that rats have higher hepato-somatic index, specific cytochrome b5 concentration, and NADPH-dependent cytochrome c (P450) activity compared to ectothermic species, SOD activity similar to those in amphibians, and specific concentration of cytochrome P450 and catalase activity lower than in a toad, but higher than in fishes and a frog. Our data indicate that tropical fishes may have reduced xenobiotic-metabolizing ability compared to the rat and amphibians. In contrast to fish and rat, amphibians have a low ratio (< 0.5) of cytochrome b5 concentration to that of P450. Most species showed cytochrome b5 sensitivity to oxygen. Thus, the use of sodium dithionate as a reducer, rather than NADPH, may be preferential in b5 determinations.
Assuntos
Antioxidantes/metabolismo , Fígado/enzimologia , Oxigenases de Função Mista/metabolismo , Animais , Anuros , Feminino , Peixes , Masculino , Ratos , Ratos Wistar , Fatores Sexuais , Especificidade da EspécieRESUMO
The cytotoxicity of two nitroheterocyclic compounds (NHCD), Nitracrine, 1-nitro-9(3'3'-dimethylaminopropylamino) acridine (Polfa, Poland) and Quinifuryl, 2-(5'-nitro-2'-furanyl) ethenyl-4-[N-[4-(N,N-diethylamino)-1'-methylbutyl] carbamoyl] quinoline (Dr. N. M. Sukhova, Institute of Organic Synthesis, Riga, Latvian Republic), towards two lines of leukaemic cells and a line of non-transformed cells, was determined under normoxia conditions. Although both drugs showed significant cytotoxicity to all cell lines (LC(50) for 24h, < or = 2 microM) with that of Nitracrine exceeding Quinifuryl, their toxicity towards murine leukaemia P388 was substantially higher, compared to murine fibroblasts NIH3T3. In addition, the rate of cell death was also two- to three-fold higher in case of P388 cells versus NIH3T3. Interestingly, human erythroleukaemia K562 cells were shown to uptake the drugs 10 min after their addition to the tissue culture medium, while the LC(50) values were reached after a substantial delay of 3h. This delay might be due to the intracellular transformation of drugs required for cell killing.