RESUMO
Sugarcane (Saccharum sp, Poaceae) is native to Southeast Asia, and due to growing demand as raw material, its cultivation recently expanded to new frontiers. The genetic diversity analysis is essential for targeting strategies in the formation and maintenance of a germplasm. This study aimed to assess the genetic diversity of 26 accessions of sugarcane from the Active Germplasm Bank of Embrapa Coastal Tablelands, using inter-simple sequence repeat (ISSR) molecular markers. Sixteen primers were used, resulting in 87 fragments with 91.13% of polymorphism. The similarity of the individuals ranged between 0.22 and 0.87. Individuals RB867515 and RB92579 were closer genetically, and the most distant ones were PI240785 and NSL 291970. Four distinct clusters were formed, using UPGMA. This information can be used to prioritize the selection of accessions for the conduction of hybridization in breeding and germplasm exchange actions.
Assuntos
Repetições de Microssatélites , Polimorfismo Genético , Saccharum/genética , Sementes/genéticaRESUMO
The plant Kielmeyera rugosa Choisy (family Calophyllaceae), popularly known as 'pau-santo', is traditionally used in Brazilian folk medicine. Recently, the dichloromethane extract-dichloromethane partition from stems of K. rugosa (KR) has shown positive results in our cytotoxic screening programme. Therefore, the aim of this study was to validate the antitumour activity of KR on sarcoma 180 tumour-bearing mice. KR showed antitumour activity with both administration routes: intraperitoneal (50 and 100 mg/kg/day) and oral (100 and 200 mg/kg/day). Tumour growth inhibition rates were 40.8-34.9% and 25.4-51.8% after intraperitoneal and oral administrations, respectively. Treatment with KR did not significantly affect body mass, macroscopy of the organs or blood leukocyte counts. In conclusion, KR exhibited an in vivo antitumour effect without substantial toxicity.
Assuntos
Divisão Celular/efeitos dos fármacos , Malpighiaceae/química , Extratos Vegetais/farmacologia , Sarcoma/patologia , Animais , Ensaios de Seleção de Medicamentos Antitumorais , CamundongosRESUMO
AIM OF THE STUDY: Orthosiphon stamineus, Benth, also known as Misai Kucing in Malaysia and Java tea in Indonesia, is traditionally used in Southeastern Asia to treat kidney dysfunctions, diabetes, gout and several other illnesses. Recent studies of Orthosiphon stamineus pharmacological profile have revealed antioxidant properties and other potentially useful biological activities thereby lending some scientific support to its use in folk medicine. So far the genotoxicity of Orthosiphon stamineus extracts has not been evaluated. In this study the genotoxic potential of Orthosiphon stamineus aqueous extract was investigated by the Salmonella/microsome mutation assay and the mouse bone marrow micronucleus test. MATERIALS AND METHODS: Chemical composition of Orthosiphon stamineus aqueous extract was analyzed by High Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD). The Salmonella/microsome assay (TA97a, TA98, TA100 and TA1535; plate incorporation method) was performed in the presence or in the absence of extrinsic metabolic activation (S9 mixture). In the mouse micronucleus assay, Orthosiphon stamineus extract was administered by gavage (0, 500, 2000 and 4000 mg/kg body weight/day for 3 days) to male and female Swiss Webster mice (N=6 per dose per sex) and bone marrow cells were harvested 24 h after the last dose. Ethoxy-resorufin-O-dealkylase (EROD) and benzyloxy-resorufin-O-dealkylase (BROD) activities were determined in mouse liver microsomes. RESULTS: The chemical analysis revealed that the Orthosiphon stamineus extract contained flavonoids (sinensetin, eupatorin), caffeic acid, and rosmarinic acid (44.00±1.879 µg/mg), the latter seemed to be one of its major constituent. Tested at doses up to 5000 µg/plate, the Orthosiphon stamineus extract was not toxic to Salmonella tester strains and did not increase the number of revertant colonies over the background incidence. In the mouse bone marrow assay, the extract did not alter the polychromatic:normochromatic erythrocytes (PCE:NCE) ratio, nor did it increase the incidence of micronucleated polychromatic erythrocytes (MNPEs). No overt toxicity and no change of CYP1A (EROD) and 2B9/10 (BROD) activities were noted. CONCLUSIONS: Based on the aforementioned findings, it is concluded that the use of Orthosiphon stamineus in the traditional medicine poses no genotoxic risk.
Assuntos
Mutagênicos/toxicidade , Orthosiphon/toxicidade , Plantas Medicinais/toxicidade , Animais , Cinamatos/química , Cinamatos/toxicidade , Depsídeos/química , Depsídeos/toxicidade , Etnofarmacologia , Feminino , Flavonoides/química , Flavonoides/toxicidade , Malásia , Masculino , Medicina Tradicional , Camundongos , Testes para Micronúcleos , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Estrutura Molecular , Testes de Mutagenicidade , Mutagênicos/química , Orthosiphon/química , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Plantas Medicinais/química , Ratos , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Ácido RosmarínicoRESUMO
We investigated the presence and inducibility of CYP1A in suckermouth catfish (Hypostomus affinis and Hypostomus auroguttatus, Loricariidae), tilapia (Oreochromis niloticus, Cichlidae) and mice (Mus musculus, Muridae). Alkoxyresorufin-O-dealkylases (EROD, MROD, PROD and BROD) were detected and proved to be inducible (beta-naphthoflavone, BNF or dimethylbenz[a]anthracene, DMBA, 50 mg/kg bw ip) in liver microsomes from tilapia and mice. In loricariids, alkoxyresorufin-O-dealkylases were either undetectable (MROD/EROD) or very low (PROD/BROD), and so they remained after treatment with BNF or DMBA. Ethoxycoumarin-O-deethylase (ECOD) was recorded in all species and proved not to be inducible by BNF or DMBA. In loricariids and tilapia, ECOD was not depressed by a concentration of alpha-naphthoflavone (CYP1A-inhibitor) that markedly depressed EROD in tilapia. A CYP1A-like protein was detected by a monoclonal antibody in rats, mice and tilapia, but not in loricariids. A polyclonal antibody, however, detected a CYP1A-like protein in liver microsomes of loricariids. Suckermouth catfish, rats, mice and tilapia express a protein reactive with a polyclonal antibody against trout CYP3A. Loricariids and tilapia exhibited marked genotoxic responses (enhanced incidence of micronucleated erythrocytes) following treatment DMBA (50 mg/kg bw ip), a promutagen activated by CYP1A/1B. Therefore, although not exhibiting EROD, a CYP1A-mediated activity, loricariids converted DMBA into its genotoxic metabolites. Our findings suggest that the CYP1A-like protein of locariid catfish recognizes DMBA, but not ethoxyresorufin, as a substrate.
Assuntos
Hidrocarboneto de Aril Hidroxilases/metabolismo , Peixes-Gato/metabolismo , Proteínas de Peixes/metabolismo , Fígado/enzimologia , Tilápia/metabolismo , O-Dealquilase 7-Alcoxicumarina/metabolismo , 9,10-Dimetil-1,2-benzantraceno/metabolismo , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Hidrocarboneto de Aril Hidroxilases/antagonistas & inibidores , Hidrocarboneto de Aril Hidroxilases/biossíntese , Benzoflavonas/farmacologia , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP2B1/metabolismo , Citocromo P-450 CYP3A/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Indução Enzimática , Inibidores Enzimáticos/farmacologia , Proteínas de Peixes/biossíntese , Cinética , Fígado/efeitos dos fármacos , Camundongos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Microssomos Hepáticos/enzimologia , Mutagênicos/metabolismo , Mutagênicos/toxicidade , Oxazinas/metabolismo , Receptores de Hidrocarboneto Arílico/agonistas , Especificidade por Substrato , beta-Naftoflavona/farmacologiaRESUMO
The synthetic peptide T-20 (enfuvirtide, EFV) represents the first compound approved by the FDA known as entry inhibitors (EIs). The resistance mutations associated with this new class of antiretroviral drug are located in the first heptad repeat (HR1) region of gp41. Amino acid changes in codons G36D/S, I37V, V38A/M/E, Q39H/R, Q40H, N42T, and N43D can confer resistance to EFV. In this work we investigated the presence of resistance mutations that occur in patients never treated with EFV and failing HAART with protease inhibitors (PIs), nucleoside reverse transcriptase (RT) inhibitors (NRTIs), and nonnucleoside RT inhibitors (NNRTIs). This knowledge can reveal whether this salvage therapy can be effective in patients failing HAART. For this, we amplified 65 samples from plasma isolates and than sequenced a fragment of 416 nt encompassing the HR1 and HR2 regions (amino acids 33-170 of gp41). The subtype distribution among the 65 isolates was 45 (69.23%) subtype B, 9 (13.85%) subtype C, 7 (10.77%) subtype F1, and 4 (6.15%) mosaics B/F1, B/C, F1/C, and C/F1/B. We found a high prevalence (7.6%) of EFV-associated mutation G36D in this cohort of patients failing HAART therapy, five isolates from subtype B (11.11% within this group). In contrast, when 1079 sequences from drug-naive patients were analyzed, only one showed the G36D substitution. This finding indicates a strong association between the selected position G36D and HAART therapy (p < 0.0001). The isolates that possess these mutations can develop resistance to EFV more rapidly. Nevertheless, more information about the impact of these mutations in salvage therapy with EFV in patients failing HAART must still be obtained.
Assuntos
Terapia Antirretroviral de Alta Atividade , Farmacorresistência Viral , Proteína gp41 do Envelope de HIV/farmacologia , Inibidores da Fusão de HIV/farmacologia , Infecções por HIV/virologia , HIV-1/genética , Mutação de Sentido Incorreto , Fragmentos de Peptídeos/farmacologia , Adulto , Sequência de Aminoácidos , Substituição de Aminoácidos/genética , Brasil , Enfuvirtida , Genótipo , Proteína gp41 do Envelope de HIV/genética , Infecções por HIV/tratamento farmacológico , HIV-1/classificação , HIV-1/efeitos dos fármacos , HIV-1/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Alinhamento de Sequência , Análise de Sequência de DNA , Falha de Tratamento , Adulto JovemRESUMO
The effects of schistosomiasis on microsomal enzymes were studied on post-infection day 90 when accumulated damage and fibrosis are most intense but granulomatous reaction around the eggs harbored in the liver is smaller than during the earlier phases. Swiss Webster (SW) and DBA/2 mice of either sex (N = 12 per sex per group) were infected with 100 Schistosoma mansoni cercariae on postnatal day 10 and killed on post-infection day 90. Cytochrome P-450 (CYP) concentration and alkoxyresorufin-O-dealkylases (EROD, MROD, BROD, and PROD), p-nitrophenol-hydroxylase (PNPH), coumarin-7-hydroxylase (COH), and UDP-glucuronosyltransferase (UGT) activities were measured in hepatic microsomes. Age-matched mice of the same sex and strain were used as controls. In S. mansoni-infected mice, CYP1A- and 2B-mediated activities (control = 100 percent) were reduced in SW (EROD: male (M) 36 percent, female (F) 38 percent; MROD: M 38 percent, F 39 percent; BROD: M 46 percent, F 19 percent; PROD: M 50 percent, F 28 percent) and DBA/2 mice (EROD: M 64 percent, F 58 percent; MROD: M 60 percent; BROD: F 49 percent; PROD: M 73 percent) while PNPH (CYP2E1) was decreased in SW (M 31 percent, F 38 percent) but not in DBA/2 mice. COH did not differ between infected and control DBA/2 and UGT, a phase-2 enzyme, was not altered by infection. In conclusion, chronic S. mansoni infection reduced total CYP content and all CYP-mediated activities evaluated in SW mice, including those catalyzed by CYP2E1 (PNPH), CYP1A (EROD, MROD) and 2B (BROD, PROD). In DBA/2 mice, however, CYP2A5- and 2E1-mediated activities remained unchanged while total CYP content and activities mediated by other CYP isoforms were depressed during chronic schistosomiasis.
Assuntos
Animais , Feminino , Masculino , Camundongos , /metabolismo , Hepatopatias Parasitárias/enzimologia , Microssomos Hepáticos/enzimologia , Esquistossomose mansoni/enzimologia , Doença Crônica , Camundongos Endogâmicos DBA , Microssomos Hepáticos/parasitologia , Fatores de TempoRESUMO
The effects of schistosomiasis on microsomal enzymes were studied on post-infection day 90 when accumulated damage and fibrosis are most intense but granulomatous reaction around the eggs harbored in the liver is smaller than during the earlier phases. Swiss Webster (SW) and DBA/2 mice of either sex (N = 12 per sex per group) were infected with 100 Schistosoma mansoni cercariae on postnatal day 10 and killed on post-infection day 90. Cytochrome P-450 (CYP) concentration and alkoxyresorufin-O-dealkylases (EROD, MROD, BROD, and PROD), p-nitrophenol-hydroxylase (PNPH), coumarin-7-hydroxylase (COH), and UDP-glucuronosyltransferase (UGT) activities were measured in hepatic microsomes. Age-matched mice of the same sex and strain were used as controls. In S. mansoni-infected mice, CYP1A- and 2B-mediated activities (control = 100%) were reduced in SW (EROD: male (M) 36%, female (F) 38%; MROD: M 38%, F 39%; BROD: M 46%, F 19%; PROD: M 50%, F 28%) and DBA/2 mice (EROD: M 64%, F 58%; MROD: M 60%; BROD: F 49%; PROD: M 73%) while PNPH (CYP2E1) was decreased in SW (M 31%, F 38%) but not in DBA/2 mice. COH did not differ between infected and control DBA/2 and UGT, a phase-2 enzyme, was not altered by infection. In conclusion, chronic S. mansoni infection reduced total CYP content and all CYP-mediated activities evaluated in SW mice, including those catalyzed by CYP2E1 (PNPH), CYP1A (EROD, MROD) and 2B (BROD, PROD). In DBA/2 mice, however, CYP2A5- and 2E1-mediated activities remained unchanged while total CYP content and activities mediated by other CYP isoforms were depressed during chronic schistosomiasis.
Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Hepatopatias Parasitárias/enzimologia , Microssomos Hepáticos/enzimologia , Esquistossomose mansoni/enzimologia , Animais , Doença Crônica , Feminino , Masculino , Camundongos , Camundongos Endogâmicos DBA , Microssomos Hepáticos/parasitologia , Fatores de TempoRESUMO
alpha-Bisabolol (BISA) is a sesquiterpene alcohol found in the oils of chamomile (Matricaria chamomilla) and other plants. BISA has been widely used in dermatological and cosmetic formulations. This study was undertaken to investigate the mutagenicity and antimutagenicity of BISA in the Salmonella/microsome assay. Mutagenicity of BISA was evaluated with TA100, TA98, TA97a and TA1535 Salmonella typhimurium strains, without and with addition of S9 mixture. No increase in the number of his+ revertant colonies over the negative (solvent) control values was observed with any of the four tester strains. In the antimutagenicity assays, BISA was tested up to the highest nontoxic dose (i.e. 50 and 150 microg/plate, with and without S9 mix, respectively) against direct-acting (sodium azide, SA; 4-nitroquinoline-N-oxide, 4-NQNO; 2-nitrofluorene, 2-NF; and nitro-o-phenylenediamine, NPD) as well as indirect-acting (cyclophosphamide, CP; benzo[a]pyrene, B[a]P; aflatoxin B1, AFB1; 2-aminoanthracene, 2-AA; and 2-aminofluorene, 2-AF) mutagens. BISA did not alter mutagenic activity of SA and of NPD, and showed only a weak inhibitory effect on the mutagenicity induced by 4-NQNO and 2-NF. The mutagenic effects of AFB1, CP, B[a]P, 2-AA and 2-AF, on the other hand, were all markedly and dose-dependently reduced by BISA. It was also found that BISA inhibited pentoxyresorufin-o-depentylase (PROD, IC50 2.76 microM) and ethoxyresorufin-o-deethylase (EROD, 33.67 microM), which are markers for cytochromes CYP2B1 and 1A1 in rat liver microsomes. Since CYP2B1 converts AFB1 and CP into mutagenic metabolites, and CYP1A1 activates B[a]P, 2-AA and 2-AF, results suggest that BISA-induced antimutagenicity could be mediated by an inhibitory effect on the metabolic activation of these promutagens.
Assuntos
Antimutagênicos/farmacologia , Salmonella typhimurium/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Hidrocarboneto de Aril Hidroxilases/antagonistas & inibidores , Citocromo P-450 CYP1A1/antagonistas & inibidores , Citocromo P-450 CYP2B1/antagonistas & inibidores , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Feminino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Sesquiterpenos Monocíclicos , Testes de Mutagenicidade/métodos , Ratos , Ratos Wistar , Salmonella typhimurium/genéticaRESUMO
Euphorbia milii (Euphorbiaceae) is a decorative plant used in gardens and living fences. In China, it has also been employed in herbal remedies for hepatitis and abdominal edema. Since E. milii latex--lyophilized or in natura--proved to be a potent plant molluscicide, its toxicity to non-target organisms has been comprehensively studied. Concerns on a possible tumor promoting activity have discouraged its use as a locally-available alternative molluscicide in schistosomiasis control programs. Two in vitro assays (inhibition of metabolic cooperation in V79 cells and Epstein-Barr virus induction in Raji cells) had suggested that E. milii latex contained tumor-promoting substances. This study was undertaken to verify whether the latex acts as a tumor promoter in vivo as well. A single dose of the initiating agent DMBA (400 nmol) was applied on the back skin of male and female DBA/2 mice. Testing for tumor promoting activity began 10 days after initiation. Tetradecanoyl phorbol acetate (TPA) (5 nmol, positive control), lyophilized latex (20, 60 and 200 microg per mouse) or acetone (vehicle control) were applied on mouse back skin twice a week for 20 weeks. In TPA-treated mice, papillomas were firstly noted during the 11th week, and by the 17th week all animals exhibited skin tumors. No tumors developed in mice treated with the solvent alone and in those exposed to latex. Findings from the present study therefore indicated that E. milii crude latex does not act as a tumor promoting agent on the mouse back skin assay.
Assuntos
Carcinógenos , Cocarcinogênese , Euphorbia , Látex/toxicidade , Papiloma/induzido quimicamente , Neoplasias Cutâneas/induzido quimicamente , 9,10-Dimetil-1,2-benzantraceno , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos DBA , Acetato de TetradecanoilforbolRESUMO
Beta-ionone (BI) is a degraded (C 13) sesquiterpene found in plant essential oils. It has been used in the synthesis of perfume chemicals and vitamin A. Recently, it was reported that BI is a rather potent in vitro inhibitor of CYP2B1-catalysed reactions in rat liver microsomes. The present study was performed to investigate whether inhibition of CYP2B1 reactions by BI could lead to an attenuation of cyclophosphamide (CP)-induced embryotoxicity in the rat. In a preliminary experiment, a dose-dependent prolongation of pentobarbital sleeping time in male and female Wistar rats suggested that BI inhibits CYP2B1 in vivo as well. In a second experiment, rats were treated by gavage with BI (0, 250, 500, 750 or 1000 mg/kg body wt) 45 min prior to a subcutaneous injection of either CP (7.5 mg/kg body wt) or its vehicle (saline) on day 11 of pregnancy. BI alone, at the highest dose tested, caused a high proportion of resorptions. Lower doses of BI, however, clearly attenuated CP-induced embryolethality and teratogenicity. These results seem to support the view that, as far as rats are concerned, CYP2B1 plays an important role in the conversion of CP into its embryolethal and teratogenic metabolites.
Assuntos
Anormalidades Induzidas por Medicamentos/prevenção & controle , Ciclofosfamida/antagonistas & inibidores , Ciclofosfamida/toxicidade , Norisoprenoides , Terpenos/farmacologia , Anormalidades Induzidas por Medicamentos/etiologia , Animais , Peso Corporal , Ciclofosfamida/farmacocinética , Citocromo P-450 CYP2B1/antagonistas & inibidores , Citocromo P-450 CYP2B1/metabolismo , Interações Medicamentosas , Inibidores Enzimáticos/farmacologia , Feminino , Morte Fetal/induzido quimicamente , Reabsorção do Feto/induzido quimicamente , Hipnóticos e Sedativos/farmacologia , Masculino , Pentobarbital/farmacologia , Gravidez , Ratos , Ratos Wistar , Sono/efeitos dos fármacosRESUMO
Annatto or urucum is an orange-yellow dye obtained from Bixa orellana seeds. It has been used as a natural dye in a variety of food products, drugs and cosmetics, and also in Brazilian cuisine as a condiment ('colorau'). Bixin, a carotenoid devoid of provitamin A activity, is the main pigment found in annatto. Some carotenoids (canthaxanthin, astaxanthin and beta-Apo-8'-carotenal) are known to be potent inducers of CYP1A1, a property not shared by others (beta-carotene, lycopene and lutein). Little is known, however, about the CYP1A1-inducing properties of bixin and annatto. The present study was performed to determine the effects of an annatto extract (28% bixin) and bixin (95% pure) on rat liver monooxygenases. Adult female Wistar rats were treated by gavage with daily doses of annatto (250 mg/kg body weight, which contains approximately 70 mg bixin/kg body weight), bixin (250 mg/kg body weight) or the vehicle only (corn oil, 3.75 g/kg body weight) for 5 consecutive days, or were not treated (untreated control). The activities of aniline-4-hydroxylase (A4H), ethoxycoumarin-O-deethylase (ECOD), ethoxy- (EROD), methoxy- (MROD), pentoxy- (PROD) and benzyloxy- (BROD) resorufin-O-dealkylases were measured in liver microsomes. Annatto (250 mg/kg containing 70 mg bixin/kg) induced EROD (3.8x), MROD (4.2x), BROD (3.3x) and PROD (2.4x). Bixin (250 mg/kg) was a weaker inducer of EROD (2.7x), MROD (2.3x) and BROD (1.9x) and did not alter PROD, A4H or ECOD activities. These results suggest that constituents of the extract other than bixin play an important role in the induction of CYP1A and CYP2B observed with annatto food colorings.
Assuntos
Carotenoides/farmacologia , Fígado/enzimologia , Microssomos Hepáticos/enzimologia , Oxigenases de Função Mista/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Bixaceae , Indução Enzimática , Feminino , Oxigenases de Função Mista/biossíntese , Ratos , Ratos WistarRESUMO
Annatto or urucum is an orange-yellow dye obtained from Bixa orellana seeds. It has been used as a natural dye in a variety of food products, drugs and cosmetics, and also in Brazilian cuisine as a condiment ('colorau'). Bixin, a carotenoid devoid of provitamin A activity, is the main pigment found in annatto. Some carotenoids (canthaxanthin, astaxanthin and á-Apo-8'-carotenal) are known to be potent inducers of CYP1A1, a property not shared by others (á-carotene, lycopene and lutein). Little is known, however, about the CYP1A1-inducing properties of bixin and annatto. The present study was performed to determine the effects of an annatto extract (28 percent bixin) and bixin (95 percent pure) on rat liver monooxygenases. Adult female Wistar rats were treated by gavage with daily doses of annatto (250 mg/kg body weight, which contains approximately 70 mg bixin/kg body weight), bixin (250 mg/kg body weight) or the vehicle only (corn oil, 3.75 g/kg body weight) for 5 consecutive days, or were not treated (untreated control). The activities of aniline-4-hydroxylase (A4H), ethoxycoumarin-O-deethylase (ECOD), ethoxy- (EROD), methoxy- (MROD), pentoxy- (PROD) and benzyloxy- (BROD) resorufin-O-dealkylases were measured in liver microsomes. Annatto (250 mg/kg containing 70 mg bixin/kg) induced EROD (3.8x), MROD (4.2x), BROD (3.3x) and PROD (2.4x). Bixin (250 mg/kg) was a weaker inducer of EROD (2.7x), MROD (2.3x) and BROD (1.9x) and did not alter PROD, A4H or ECOD activities. These results suggest that constituents of the extract other than bixin play an important role in the induction of CYP1A and CYP2B observed with annatto food colorings
Assuntos
Animais , Feminino , Ratos , Carotenoides , Fígado , Microssomos Hepáticos , Oxigenases de Função Mista/efeitos dos fármacos , Extratos Vegetais , Indução Enzimática , Oxigenases de Função Mista/biossíntese , Ratos WistarRESUMO
Xenobiotic metabolism is influenced by a variety of physiological and environmental factors including pregnancy and nutritional status of the individual. Pregnancy has generally been reported to cause a depression of hepatic monooxygenase activities. Low-protein diets and protein-energy malnutrition have also been associated with a reduced activity of monooxygenases in nonpregnant animals. We investigated the combined effects of pregnancy and protein-energy malnutrition on liver monooxygenase O-dealkylation activity. On pregnancy day 0 rats were assigned at random to a group fed ad libitum (well-nourished, WN) or to a malnourished group (MN) which received half of the WN food intake (12 g/day). WN and MN rats were killed on days 0 (nonpregnant), 11 or 20 of pregnancy and ethoxy- (EROD), methoxy- (MROD) and penthoxy- (PROD) resorufin O-dealkylation activities were measured in liver microsomes. Only minor changes in enzyme activities were observed on pregnancy day 11, but a clear-cut reduction of monooxygenase activities (pmol resorufin min-1 mg protein-1) was noted near term (day 0 vs 20, means + or _ SD, Student t-test, P<0.05) in WN (EROD: 78.9 + or - 15.1 vs 54.6 + or - 10.2; MROD: 67.8 + or - 10.0 vs 40.9 + or - 7.2; PROD: 6.6 + or - 0.9 vs 4.3 + or - 0.8) and in MN (EROD: 89.2 + or - 23.9 vs 46.9 + or - 15.0; MROD: 66.8 + or - 13.8 vs 27.9 + or - 4.4; PROD: 6.3 + or - 1.0 vs 4.1 + or - 0.6) dams. On pregnancy day 20 MROD was lower in MN than in WN dams. Malnutrition did not increase the pregnancy-induced reduction of EROD and PROD activities. Thus, the present results suggest that the activities of liver monooxygenases are reduced in near-term pregnancy and that protein-energy malnutrition does not alter EROD or PROD in pregnant rats