RESUMEN
Vernonia cinerea has been widely used in traditional medicines for various diseases and shown to aid in smoking abstinence and has anticancer properties. V. cinerea bioactive compounds, including flavonoids and hirsutinolide-type sesquiterpene lactones, have shown an inhibition effect on the nicotine-metabolizing cytochrome P450 2A6 (CYP2A6) enzyme and hirsutinolides reported suppressing cancer growth. In this study, V. cinerea ethanol extract and its bioactive compounds, including four flavonoids and four hirsutinolides, were investigated for an inhibitory effect on human liver microsomal CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 using cocktail inhibition assays combined with LC-MS/MS analysis. Among tested flavonoids, chrysoeriol was more potent in inhibition on CYP2A6 and CYP1A2 than other liver CYPs, with better binding efficiency toward CYP2A6 than CYP1A2 (Ki values in competitive mode of 1.93 ± 0.05 versus 3.39 ± 0.21 µM, respectively). Hirsutinolides were prominent inhibitors of CYP2A6 and CYP2D6, with IC50 values of 12-23 and 15-41 µM, respectively. These hirsutinolides demonstrated time-dependent inhibition, an indication of mechanism-based inactivation, toward CYP2A6. Quantitative prediction of microsomal metabolism of these flavonoids and hirsutinolides, including half-lives and hepatic clearance rate, was examined. These findings may have implications for further in vivo studies of V. cinerea. Copyright © 2017 John Wiley & Sons, Ltd.
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Microsomas Hepáticos/efectos de los fármacos , Vernonia/química , Humanos , Microsomas Hepáticos/patologíaRESUMEN
Modulation of drug transporters via herbal medicines which have been widely used in combination with conventional prescription drugs may result in herb-drug interactions in clinical practice. The present study was designed to investigate the inhibitory effects of 50 major herbal constituents on P-glycoprotein (P-gp) in vitro and in vivo as well as related inhibitory mechanisms. Among these herbal medicines, four constituents, including emodin, 18ß-glycyrrhetic acid (18ß-GA), dehydroandrographolide (DAG), and 20(S)-ginsenoside F1 [20(S)-GF1] exhibited significant inhibition (>50%) on P-gp in MDR1-MDCKII and Caco-2 cells. Emodin was the strongest inhibitor of P-gp (IC50=9.42 µM), followed by 18ß-GA (IC50=21.78 µM), 20(S)-GF1 (IC50=76.08 µM) and DAG (IC50=77.80 µM). P-gp ATPase activity, which was used to evaluate the affinity of substrates to P-gp, was stimulated by emodin and DAG with Km and Vmax values of 48.61, 29.09 µM and 71.29, 38.45 nmol/min/mg protein, respectively. However, 18ß-GA and 20(S)-GF1 exhibited significant inhibition on both basal and verapamil-stimulated P-gp ATPase activities at high concentration. Molecular docking analysis (CDOCKER) further elucidated the mechanism for structure-inhibition relationships of herbal constituents with P-gp. When digoxin was co-administered to male SD rats with emodin or 18ß-GA, the AUC(0ât) and Cmax of digoxin were increased by approximately 51% and 58%, respectively. Furthermore, 18ß-GA, DAG, 20(S)-GF1 and Rh1 at 10 µM significantly inhibited CYP3A4/5 activity, while emodin activated the metabolism of midazolam in human liver microsomes. In conclusion, four herbal constituents demonstrated inhibition of P-gp to specific extents in vitro and in vivo. Taken together, our findings provided the basis for the reliable assessment of the potential risks of herb-drug interactions in humans.
Asunto(s)
Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Diterpenos/efectos adversos , Emodina/efectos adversos , Ginsenósidos/efectos adversos , Ácido Glicirretínico/análogos & derivados , Interacciones de Hierba-Droga , Subfamilia B de Transportador de Casetes de Unión a ATP/antagonistas & inhibidores , Animales , Área Bajo la Curva , Células CACO-2 , Línea Celular Tumoral , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Digoxina/administración & dosificación , Ácido Glicirretínico/efectos adversos , Humanos , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/patología , Conformación Proteica , Ratas , Verapamilo/administración & dosificaciónRESUMEN
Acetaminophen (APAP) overdose is the most frequent cause of adult acute liver failure. Susceptibility or resistance to APAP toxicity is most likely accounted for by the interplay of several factors. One factor important in multiple different chronic liver diseases that may play a role in APAP toxicity is elevated hepatic iron. Hereditary hemochromatosis is traditionally associated with hepatic iron overload. However, varying degrees of elevated hepatic iron stores observed in chronic hepatitis C and B, alcoholic liver disease and nonalcoholic fatty liver disease also have clinical relevance. We employed an animal model in which mice are fed a 3,5,5-trimethyl-hexanoyl-ferrocene (TMHF)-supplemented diet to evaluate the effect of elevated hepatic iron on APAP hepatotoxicity. Three hundred milligrams per kilogram APAP was chosen because this dosage induces hepatotoxicity but is not lethal. Since both excess iron and APAP induce oxidative stress and mitochondrial dysfunction, we hypothesized that the TMHF diet would enhance APAP hepatotoxicity. The results were the opposite. Centrilobular vacuolation/necrosis, APAP adducts, nitrotyrosine adducts, and a spike in serum alanine aminotransferase, which were observed in control mice treated with APAP, were not observed in TMHF-fed mice treated with APAP. Further analysis showed that the levels of CYP2E1 and CYP1A2 were not significantly different in TMHF-treated compared with control mice. However, the magnitude of depletion of glutathione following APAP treatment was considerably less in TMHF-treated mice than in mice fed a control diet. We conclude that a TMHF diet protects mice from moderate transient APAP-induced hepatotoxicity prior to the formation of APAP adducts, and one contributing mechanism is reduction in glutathione depletion.
Asunto(s)
Acetaminofén/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Suplementos Dietéticos , Compuestos Ferrosos/uso terapéutico , Hierro/metabolismo , Hígado/efectos de los fármacos , Análisis de Varianza , Animales , Western Blotting , Enfermedad Hepática Inducida por Sustancias y Drogas/enzimología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Modelos Animales de Enfermedad , Compuestos Ferrosos/administración & dosificación , Glutatión/metabolismo , Inmunohistoquímica , Hígado/enzimología , Hígado/metabolismo , Hígado/patología , Pruebas de Función Hepática , Masculino , Metalocenos , Ratones , Ratones Endogámicos C57BL , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Microsomas Hepáticos/metabolismo , Microsomas Hepáticos/patologíaRESUMEN
Naringenin is a flavanone that is believed to have many biological actions, including as an anti-oxidant, free radical scavenger and an antiproliferative agent. The global incidence of gastric carcinoma is increasing rapidly, more than for any other cancer. Therefore, in the present study, we tested the effects of naringenin on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and saturated sodium chloride (S-NaCl) in rats. Male Wistar rats were divided into five groups and treated over a period of 20 weeks as follows: (i) a control group given corn oil (1 mL/rat, p.o.) daily 20 weeks; (ii) 200 mg/kg, p.o., MNNG on Days 0 and 14 with S-NaCl (1 mL/rat) administered twice a week for the first 3 weeks; (iii) 200 mg/kg, p.o., MNNG on Days 0 and 14, with naringenin (200 mg/kg, p.o., daily) treatment for the entire 20 weeks; (iv) 200 mg/kg, p.o., MNNG on Days 0 and 14, with naringenin treatment (200 mg/kg, p.o., daily) initiated from 6 to 20 weeks; (v) 200 mg/kg, p.o., naringenin alone daily for 20 weeks. In Group II rats in which gastric cancer was inducted with MNNG and S-NaCl, there was a significant increase in hydrogen peroxide and lipid peroxidation levels, with decreases in reduced glutathione, oxidized glutathione, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase. In addition, in Group II rats with gastric cancer, there were significant increases in the activity of cytochrome P450, cytochrome b(5) and NADPH cytochrome c reductase, with concomitant decreases in the activity of the phase II enzymes glutathione S-transferase and UDP-glucuronosyl transferase. Naringenin treatment (Groups III and IV) restored enzyme activity to near control levels. These results indicate that naringenin has a chemopreventive action against MNNG-induced gastric carcinoma in experimental rats.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Flavanonas/uso terapéutico , Metilnitronitrosoguanidina/toxicidad , Cloruro de Sodio/toxicidad , Neoplasias Gástricas/inducido químicamente , Neoplasias Gástricas/tratamiento farmacológico , Animales , Activación Enzimática/efectos de los fármacos , Activación Enzimática/fisiología , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/fisiología , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Microsomas Hepáticos/patología , Plantas Medicinales/química , Ratas , Ratas Wistar , Neoplasias Gástricas/enzimologíaRESUMEN
The antiangiogenic effect of Lygodium flexuosum extract was evaluated in Wistar rats intoxicated with N-nitrosodiethylamine (NDEA) in preventive and curative models. In preventive groups, NDEA was administered for 20 weeks. Daily doses of L. flexuosumn-hexane extract (200mg/kg) started 1 week before the onset of NDEA intoxication and continued for 20 weeks. In curative animals, NDEA was administered for 20 weeks followed by treatment with the n-hexane extract of L. flexuosum for 28 days. Rats intoxicated with NDEA had elevated levels of serum gamma-GT, AST, ALT, LDH levels and hepatic MDA and decreased levels of hepatic GSH. When treated with L. flexuosum extract had normal levels of gamma-GT, AST, ALT, LDH levels, hepatic MDA and GSH. NDEA administered rat liver showed an overexpressed levels of angiopoietins 1 (Ang-1) and 2 (Ang-2) and its receptor Tie-2 mRNA. L. flexuosum extract treatment significantly (pAsunto(s)
Inhibidores de la Angiogénesis/farmacología
, Helechos/química
, Neoplasias Hepáticas Experimentales/inducido químicamente
, Microsomas Hepáticos/efectos de los fármacos
, Extractos Vegetales/farmacología
, 3,4-Metilenodioxianfetamina/metabolismo
, Alanina Transaminasa/sangre
, Angiopoyetina 1/sangre
, Angiopoyetina 2/sangre
, Animales
, Aspartato Aminotransferasas/sangre
, Dietilnitrosamina
, Glutatión/sangre
, L-Lactato Deshidrogenasa/sangre
, Microsomas Hepáticos/metabolismo
, Microsomas Hepáticos/patología
, ARN Mensajero/sangre
, Ratas
, Ratas Wistar
, Receptor TIE-2/sangre
, Factores de Tiempo
, gamma-Glutamiltransferasa/sangre
RESUMEN
Rhinax, a herbal formulation, was investigated for its protective activity against CCl4-induced liver injury and survival in rats. Oral administration of Rhinax at a dose of 80 mg/kg significantly reduces the hepatotoxic effects of CCl4. It also significantly improves the survival of rats at a dose of 160 mg/kg. On the basis of these observations, we conclude that Rhinax possesses anti-hepatotoxic activity and that the observed activity may be due to the increased activity of cytochrome P450, thereby exerting an inhibitory effect on reductive pathways of CCl4.
Asunto(s)
Tetracloruro de Carbono/toxicidad , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Administración Oral , Animales , Aspartato Aminotransferasas/sangre , Tetracloruro de Carbono/administración & dosificación , Sistema Enzimático del Citocromo P-450/metabolismo , Modelos Animales de Enfermedad , Hígado/patología , Hepatopatías/tratamiento farmacológico , Hepatopatías/mortalidad , Masculino , Medicina Ayurvédica , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Microsomas Hepáticos/patología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Plantas Medicinales/química , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
The current investigation furnishes a good correlation between the alpha-tocopherol content of the liver and microsomes and corresponding inhibition of Russell's viper venom phospholipase A2 inflicted damage to them. Dietary supplementation of d1-alpha-tocopherol at a concentration of 100 mg and 200 mg per kg of diet displayed less damage caused by venom phospholipase A2 in sharp contrast to the vitamin E deficient rats. alpha-tocopherol due presumably to the formation of complexes with the phospholipid hydrolysis products of the membranes, plays a significant role in membrane stabilization.
Asunto(s)
Metabolismo de los Lípidos , Hígado/efectos de los fármacos , Microsomas Hepáticos/efectos de los fármacos , Fosfolipasas A/toxicidad , Venenos de Víboras/toxicidad , Vitamina E/farmacología , Animales , Colesterol/metabolismo , Suplementos Dietéticos , Membranas Intracelulares/efectos de los fármacos , Membranas Intracelulares/metabolismo , Membranas Intracelulares/patología , Hígado/metabolismo , Hígado/patología , Microsomas Hepáticos/metabolismo , Microsomas Hepáticos/patología , Fosfolipasas A2 , Fosfolípidos/metabolismo , Ratas , Ratas Wistar , Vitamina E/administración & dosificaciónRESUMEN
The present study was designed to examine the incorporation of phytosterols (PS) in membranes and tissues of rats fed a diet containing 2% PS in the presence of 0.2% cholic acid for 22 days. The control diet contained 12 mg PS/100 g compared with 2,012 mg/100 g. Liver, kidney, testis, and prostate microsomes, plasma, and epididymal fat pads were examined for sterols. Fatty acid composition and phospholipid pattern were also examined in some tissues. The PS diet resulted in a fivefold increase in plasma PS compared with controls. PS was found to accumulate in adipose tissue and liver microsomes in rats fed the PS-supplemented diet. There was no effect of PS incorporation on microsomal cholesterol content, except in the testes, in which dietary PS reduced cholesterol content by 25%. Dietary PS increased 20:4n-6 and 22:5n-3 fatty acids in membranes of the liver, testis, and prostate but decreased 16:1 in liver microsomes. PS incorporation had no effect on the phospholipid pattern of the liver and testis.
Asunto(s)
Dieta , Ácidos Grasos/análisis , Fitosteroles/farmacocinética , Esteroles/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Estudios de Cohortes , Ácidos Grasos/clasificación , Hígado/química , Hígado/patología , Masculino , Microsomas Hepáticos/química , Microsomas Hepáticos/patología , Fitosteroles/administración & dosificación , Próstata/química , Próstata/patología , Ratas , Ratas Sprague-Dawley , Esteroles/clasificación , Testículo/química , Testículo/patologíaRESUMEN
This study evaluated levo-alpha-noracetylmethadol (NorLAAM), the first N-demethylated metabolite of levo-alpha-acetylmethadol (LAAM), a long-acting morphine-like (mu) agonist, approved in 1993 to treat opiate dependence. After acute and 7-day pilot studies to define dose levels appropriate for use in longer term evaluations, Sprague-Dawley rats (20 of each sex per group) were gavaged with doses of 4.4-25.9 mg kg(-1) day(-1) for 30 days followed by a 14-day recovery period. Treatment-related effects included dose-dependent CNS depression paralleled by changes in food consumption, body weight gain and fecal output, as well as reddish urine and abdominal staining. Tolerance developed by day 7. The spectrum of activity observed differed from the parent compound primarily in its time course. Cage-biting and gnawing behavior were observed only with NorLAAM. Mortality was dose-dependent, with deaths occurring predominantly during the first week. At day 30, all male-treated groups exhibited statistically significant, dose-dependent decreases in body weight gain and increases in serum cholesterol that returned to the control range following recovery. Increases in brain/body weight and testes/body weight ratios and decreases in kidney/brain, liver/brain, spleen/brain and heart/brain ratios, as well as decreases in kidney, liver, spleen and heart absolute weights, achieved statistical significance only for males. At terminal sacrifice, histological findings in the kidneys included increased incidences of tubular mineral deposition in mid- and high-dose groups of both sexes and of corticomedullary mineral deposition in females. Hepatic centrilobular hypertrophy was evident in male and female mid- and high-dose groups. Histopathological changes abated following the recovery period. In summary, acute and repeated administration of NorLAAM produced a pharmacodynamic profile commensurate with its role as the primary N-demethylated metabolite of LAAM, which is more potent and less lipophilic than the parent compound; this was reflected in the toxicological outcomes observed. Like LAAM, NorLAAM's overall pattern of activity is consistent with its activity as a mu-agonist, which stimulates hepatic microsomal enzymes in rodents.
Asunto(s)
Analgésicos Opioides/toxicidad , Sistema Nervioso Central/efectos de los fármacos , Acetato de Metadil/análogos & derivados , Microsomas Hepáticos/efectos de los fármacos , Receptores Opioides mu/antagonistas & inhibidores , Administración Oral , Analgésicos Opioides/administración & dosificación , Animales , Conducta Animal/efectos de los fármacos , Colesterol/sangre , Relación Dosis-Respuesta a Droga , Tolerancia a Medicamentos , Ingestión de Alimentos/efectos de los fármacos , Heces/química , Femenino , Masculino , Acetato de Metadil/administración & dosificación , Acetato de Metadil/toxicidad , Microsomas Hepáticos/enzimología , Microsomas Hepáticos/patología , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Factores Sexuales , Distribución Tisular , Aumento de Peso/efectos de los fármacosAsunto(s)
Hidrocarburo de Aril Hidroxilasas , Benzoquinonas/farmacología , Peroxidación de Lípido/efectos de los fármacos , Hígado , Malondialdehído/análisis , Microsomas Hepáticos/metabolismo , Soluciones Preservantes de Órganos , Preservación de Órganos/métodos , Probucol/farmacología , Adenosina , Alopurinol , Animales , Western Blotting , Citocromo P-450 CYP3A , Sistema Enzimático del Citocromo P-450/análisis , Sistema Enzimático del Citocromo P-450/metabolismo , Radicales Libres , Glutatión , Glutatión Transferasa/análisis , Glutatión Transferasa/metabolismo , Insulina , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/patología , Oxidorreductasas N-Desmetilantes/análisis , Oxidorreductasas N-Desmetilantes/metabolismo , Rafinosa , Ratas , Ratas Wistar , Ubiquinona/análogos & derivadosRESUMEN
Adriamycin (25 microM) stimulated NADPH-dependent microsomal lipid peroxidation about fourfold over control values. The tested antioxidants, zinc, superoxide dismutase, vitamin E, and desferrioxamine (Desferal) inhibited Adriamycin-enhanced lipid peroxidation to varying degrees. Others antioxidants, e.g., glutathione, catalase, and selenium, were found to have no effects. Our in vitro studies suggest that adriamycin effect is mediated by a complex oxyradical cascade involving superoxide, hydroxyl radical, and small amounts of iron.
Asunto(s)
Antioxidantes/farmacología , Doxorrubicina/toxicidad , Peroxidación de Lípido/efectos de los fármacos , Microsomas Hepáticos/efectos de los fármacos , Animales , Catalasa/farmacología , Deferoxamina/farmacología , Relación Dosis-Respuesta a Droga , Glutatión/farmacología , Cinética , Ratones , Ratones Endogámicos , Microsomas Hepáticos/metabolismo , Microsomas Hepáticos/patología , NADP/metabolismo , Selenio/farmacología , Superóxido Dismutasa/farmacología , Vitamina E/farmacología , Zinc/farmacologíaRESUMEN
The rat intragastric feeding model for alcoholic liver disease was used to study the effect of different diets on the fatty acid composition of liver microsomes. Rats were fed corn oil and ethanol (CE), saturated fat and ethanol (SF+E) or corn oil and dextrose (CD) for either 2 or 4 weeks. Rats were also fed saturated and dextrose (SF+D) for 4 weeks. In comparison with the CD diet, lower levels of arachidonic acid were detected in rats fed the CE, SF+E, and SF+D diets. However, the diet-induced changes in levels of arachidonic acid varied as a function of length of feeding. In rats fed the CE diet, we detected a significant decrease in the level of arachidonic acid compared with CD animals. Conversely, in rats fed the SF+E diet, the level of arachidonic acid increased compared with the SF+D group. In addition, a significant correlation was noted between levels of oleic acid and arachidonic acid in both corn oil (r = -0.85, p < 0.01) and saturated fat (r = -0.76, p < 0.05) groups. However, the changes in levels of arachidonic acid and oleic acid were in opposite directions in the two groups. Levels of docosahexaenoic acid decreased between the 2 and 4 weeks in animals maintained on the CE diet. Levels of stearic acid increased between 2 and 4 weeks in rats fed the SF+E diet. The lowest level of linoleic acid was detected in the SF+D and SF+E groups, but levels of linoleic acid remained constant in all groups throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Alcoholismo/patología , Grasas de la Dieta/administración & dosificación , Ácidos Grasos/metabolismo , Cirrosis Hepática Alcohólica/patología , Microsomas Hepáticos/patología , Animales , Ácido Araquidónico/metabolismo , Aceite de Maíz/administración & dosificación , Aceite de Maíz/efectos adversos , Grasas de la Dieta/efectos adversos , Hígado/patología , Masculino , Ratas , Ratas WistarRESUMEN
In this study, the generalized Shwartzman reaction of rabbit induced by endotoxin of Escherichia Coli was built as DIC models. The experiment showed that the levels of lipid peroxide (LPO) in the hepatocytic microsomes of model group were increased significantly, whereas the cytochrome P-450 (Cyto. P-450) contents and aniline hydroxylase activities were obviously decreased. In the Re Du Qing (RDQ) group and dexamethasone group the decrease of LPO in hepatocytic microsomes as well as the reduction of Cyto. P-450 contents and aniline hydroxylase activities were alleviated. Furthermore, the correlation analysis indicated a significant negative correlation between levels of LPO in microsomes and the Cyto. P-450 contents as well as aniline hydroxylase activities. This study indicates the LPO may play an important role in the damage of hepatocytic microsomes and RDQ could prevent hepatocytic microsomes from injury of rabbits with endotoxin-induced DIC.
Asunto(s)
Coagulación Intravascular Diseminada/patología , Medicamentos Herbarios Chinos/farmacología , Microsomas Hepáticos/patología , Animales , Sistema Enzimático del Citocromo P-450/metabolismo , Coagulación Intravascular Diseminada/inducido químicamente , Coagulación Intravascular Diseminada/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Endotoxinas , Escherichia coli , Femenino , Peróxidos Lipídicos/metabolismo , Hígado/patología , Masculino , Microsomas Hepáticos/metabolismo , ConejosRESUMEN
The effect(s) of an intraperitoneal (i.p.) administration of aqueous extracts of two Nigerian medicinal plants, Garcina cola and Vermonia amygdalina on the level of glucose-6-phosphatase activity, total protein content and regenerative and total DNA concentrations, was determined in liver homogenates of partially-hepatectomized and normal albino rat liver. The established control curves for the DNA and microsome syntheses rates after partial hepatectomy showed two waves of synthetic activity; the first occurring at 24 hrs., and the second at 32 hrs as judged by total regenerative DNA concentration and glucose-6-phosphatase activity. Garcina cola significantly inhibited the first wave of microsome and DNA syntheses by 31% and 24% respectively in a dose-related manner. However, the degree of inhibition of glucose-6-phosphatase activity by Garcina cola was substantially reduced in normal rat liver when administered simultaneously with carbon tetrachloride. Dilute and concentrated extracts of Vermonia amygdalina, on the other hand, elevated the levels of glucose-6-phosphatase activity in normal rat liver by 44% and 54%, respectively over the controls. Total DNA concentration was similarly increased, though to a lesser degree. The implication of these results are discussed in relation to the structural similarity of the furocoumarins contained in these plants to AFB1, and their likely modes of action.
Asunto(s)
ADN/efectos de los fármacos , Glucosa-6-Fosfatasa/metabolismo , Regeneración Hepática , Microsomas Hepáticos/efectos de los fármacos , Extractos Vegetales/toxicidad , Plantas Medicinales , Animales , Tetracloruro de Carbono/toxicidad , Carcinógenos , ADN/biosíntesis , ADN/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Glucosa-6-Fosfatasa/antagonistas & inhibidores , Masculino , Microsomas Hepáticos/enzimología , Microsomas Hepáticos/patología , Nigeria , RatasRESUMEN
Two experiments were conducted to reevaluate the dietary vitamin E requirement of fingerling channel catfish. Purified diets containing 1% cod liver oil, 4% stripped lard and adequate selenium supplemented with graded levels of DL-alpha-tocopheryl acetate were used in both experiments. The results indicate that the previously reported requirement value, which was based on growth and pathological changes, was underestimated. The minimum dietary vitamin E requirement in the form of DL-alpha-tocopheryl acetate was determined to be 50 mg/kg of diet based on 16-week liver microsomal ascorbic acid-stimulated lipid peroxidation data. No differences were observed in growth rates or feed efficiencies in either experiment. No gross pathologies or hematological changes were evident in fish fed different levels of vitamin E for 20 weeks, except red blood cell hemolysis, which was elevated at the lower levels. Histological lesions were only observed in fish receiving the 0 mg/kg diet. A marked multifocal splenic hemosiderosis was observed in these fish. A mild multi-focal hemosiderosis was observed in the pancreatic tissue surrounding the hepatic vasculature. The pancreatic tissue appeared reduced from that observed in fish fed higher levels of vitamin E. No significant lesions were observed in the other tissues examined.