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1.
Molecules ; 25(6)2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32168847

RESUMO

The aim of this study was to compare the protective effects of chokeberry juice and silymarin against chemical-induced liver fibrosis in rats. Liver fibrosis was induced by CCl4 administered two days a week for six weeks. Two groups of rats were co-treated with chokeberry juice, 10 mL/kg/day. or silymarin as a positive control, 100 mg/kg/day for six weeks. Hepatic lipid peroxidation was suppressed by 50% and the activity of hepatic antioxidant enzymes was increased by 19%-173% in rats co-treated with CCl4 and substances tested as compared to rats administered CCl4 alone. Hepatic hydroxyproline was decreased by 24% only in rats treated with silymarin. The messenger RNA (mRNA) expression levels of fibrosis-related molecules, procollagen I, α-SMA, TIMP-1, TGFß, and TNFα, which were significantly increased in the liver of CCl4-treated rats, were not modulated by substances tested. Histological evaluation revealed a slight protective effect of silymarin against fibrosis. However, in CCl4 + chokeberry-treated rats, the density of vacuolated hepatocytes was significantly lower than that in silymarin administered animals. Chokeberry juice did not demonstrate an antifibrotic effect in the applied experimental model of fibrosis, and the effect of the known antifibrotic agent, silymarin, was very limited.

2.
In Vivo ; 30(6): 807-812, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27815465

RESUMO

BACKGROUND/AIM: The leaves of white mulberry (Morus alba L.) contain various polyphenolic compounds possessing strong antioxidant activity and anticancer potential. This study was designed to investigate the chemopreventive effect of aqueous extract of mulberry leaves against N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis. MATERIALS AND METHODS: Wistar rats were divided into four groups: control, mulberry extract-treated, NDEA-treated, and mulberry extract plus NDEA-treated. Mulberry extract was given in the diet (1,000 mg/kg b.w./day); NDEA was given in drinking water. RESULTS: Mulberry extract reduced the incidence of hepatocellular carcinoma, dysplastic nodules, lipid peroxidation, protein carbonyl formation, and DNA degradation. Treatment with mulberry leaf extract along with NDEA challenge did not affect the activity of antioxidant enzymes and glutathione content. CONCLUSION: Treatment with mulberry leaf extract partially protected the livers of rats from NDEA-induced hepatocarcinogenesis and a direct antioxidant mechanism appears to contribute to its anticarcinogenic activity.


Assuntos
Carcinoma Hepatocelular/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , Morus/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Carcinoma Hepatocelular/induzido quimicamente , DNA/metabolismo , Dietilnitrosamina , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/induzido quimicamente , Masculino , Substâncias Protetoras/farmacologia , Carbonilação Proteica/efeitos dos fármacos , Ratos Wistar
3.
J Med Food ; 19(3): 330-6, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26987026

RESUMO

The article presents an evaluation of the safety of yellow tea (Camellia sinensis) extract consumption and its antioxidant activity in an animal model. Wistar rats were exposed through diet to 2, 6, and 10 g yellow tea extract/kg feed for 90 days. No signs of toxicity and no differences in mean body weight gain in the treated and control rats were recorded throughout the experiment. No statistically significant differences in hematology findings and clinical chemistry parameters were observed between controls and treated groups. Microscopic examination of tissue sections revealed no pathology attributable to yellow tea extract intake. Lipid peroxidation level in the liver was slightly increased in medium-dose males and high-dose females and decreased in two female groups receiving 2 and 6 g/kg of the extract tested. Content of carbonyl groups in protein, as well as the basal level of DNA damage, was not changed. In a majority of rats, the activity of antioxidant enzymes was increased except superoxide dismutase in high-dose groups, glutathione peroxidase in high-dose females, glutathione reductase in low- and mid-dose groups, and glutathione S-transferase in mid-dose females and high-dose males. It could be concluded that rats tolerated well dietary treatment with yellow tea extract up to 0.8 g/kg b.w./day for 90 days. Results showed that yellow tea extract at the doses tested did not demonstrate adverse effects and improved the antioxidant status in the liver of rats.


Assuntos
Antioxidantes/metabolismo , Camellia sinensis/metabolismo , Extratos Vegetais/metabolismo , Animais , Antioxidantes/efeitos adversos , Camellia sinensis/efeitos adversos , Camellia sinensis/química , Feminino , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Extratos Vegetais/efeitos adversos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
4.
Plant Foods Hum Nutr ; 71(1): 13-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26880214

RESUMO

Ferritin-iron is currently considered as one of the most promising iron forms to prevent iron deficiency anaemia. We found that the cultivation of soybean seeds in a solution of ferrous sulfate results in material with extremely high iron content - 560.6 mg Fe/100 g of dry matter, while ferritin iron content was 420.5 mg/100 g dry matter. To assess the potential adverse effects of a preparation containing such a high concentration of iron, male and female Wistar rats were exposed via diet to 10, 30, 60 g soybean sprouts powder/kg feed for 90 days. There were no differences in final body weight and mean food consumption between controls and rats administered sprouts. No statistically significant differences in haematology and clinical chemistry parameters were found between controls and treated rats. Microscopic examination of 22 tissues did not reveal any pathology due to soybean sprouts intake. Long term administration of the test material did not cause oxidative damage to DNA and protein in the liver as evidenced by the unchanged basal levels of DNA damage as well as carbonyl groups content. Lipid peroxidation was slightly increased only in females. The activity of several antioxidant enzymes: superoxide dismutase, glutathione peroxidase and glutathione S-transferase was increased, which substantially enhanced the antioxidant status in the liver from the rats treated with soybean sprouts. Hence, the material tested can be recommended as a component of food supplements for individuals with iron deficiency anaemia and inflammatory bowel diseases.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Ferritinas/efeitos adversos , Alimento Funcional/efeitos adversos , Ferro/efeitos adversos , Soja/química , Anemia Ferropriva/sangue , Animais , Antioxidantes/metabolismo , Dano ao DNA/efeitos dos fármacos , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Compostos Ferrosos/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Pós/efeitos adversos , Ratos , Ratos Wistar , Plântula/química , Plântula/metabolismo , Sementes/química , Sementes/metabolismo , Soja/metabolismo
5.
Pharm Biol ; 54(9): 1891-900, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26839940

RESUMO

Context Yellow tea containing the same catechins as other types of tea but in different proportions has been suggested to possess potent anticancer activities. Objective This study investigates the chemopreventive effect of yellow tea aqueous extract against N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis in rats by employing histological and biochemical methods. Materials and methods Wistar rats were divided randomly into four groups: control (I), yellow tea (II), NDEA (III), and yellow tea + NDEA (IV). Groups II and IV were exposed via a diet to yellow tea extract in a concentration of 10 g/kg feed; groups III and IV received 0.01% NDEA in drinking water. The experiment lasted for 13 weeks. Results Daily intake of yellow tea in an average dose of 800 mg/kg b.w. alleviated the carcinogenic effect of NDEA as evidenced by reversed histopathological changes towards normal hepatocellular architecture and decreased lipid peroxidation, protein carbonyl formation, and DNA degradation by 64%, 37% and 15%, respectively, as compared with values obtained in NDEA alone-treated rats. Treatment with yellow tea extract caused protection of superoxide dismutase (SOD) and catalase (CAT); their activity was recovered by 47% and 12%, respectively, as compared with the NDEA-treated rats. Moreover, the extract normalized the NDEA-induced activity of paraoxonase 1 (PON1) and glutathione peroxidase (GPx), while a further increase in the level of reduced glutathione (GSH) was noticed. Conclusions On the basis of these findings, it can be concluded that treatment with yellow tea partially protected the livers of rats from NDEA-induced hepatocarcinogenesis and that its antioxidant activity contributed to this effect.


Assuntos
Anticarcinógenos/farmacologia , Antioxidantes/farmacologia , Camellia sinensis , Transformação Celular Neoplásica/efeitos dos fármacos , Dietilnitrosamina , Neoplasias Hepáticas Experimentais/prevenção & controle , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Anticarcinógenos/isolamento & purificação , Antioxidantes/isolamento & purificação , Biomarcadores/sangue , Camellia sinensis/química , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Dano ao DNA/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas Experimentais/sangue , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Carbonilação Proteica/efeitos dos fármacos , Ratos Wistar
6.
Acta Pol Pharm ; 72(2): 267-76, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26642677

RESUMO

UNLABELLED: Cloudy apple juice (CAJ) is a rich source of nutrients as well as non-nutrient components including high quantity of polyphenols, particularly oligomeric procyanidins, which are considered as potential chemopreventive agents that protect against the action of chemical carcinogens. The aim of this study was to examine the effect of CAJ alone or in combination with hepatocarcinogenic N-nitrosodiethylamine (NDEA) on liver damage biomarkers, including DNA damage, and the phase I and II enzymes in rat. The forced feeding with CAJ alone for 28 days, has slightly reduced the activities of phase I enzymes, MROD (CYP1A2 biomarker) and PNPH (CYP2El biomarker), while phase II enzymes, glutathione S-transferase (GST) and NAD(P)H: quinone oxidoreductase-1 (NQO1), were elevated. Combined treatment of rats with CAJ and NDEA significantly reduced the levels of hepatic ALT and SDH (by ~100%) as compared to values from NDEA-treated animals. CAJ pretreatment further increased the PROD (CYP2B biomarker) and NQO1 activities increased by NDEA administration. Modulation of enzymes activities was accompanied by the changes in the proteins levels. These results indicate that CAJ may protect liver against damage induced by NDEA. Moreover, a significant decrease of SDH activity by CAJ may confirm its potential anti-diabetic activity.


Assuntos
Anticarcinógenos/farmacologia , Bebidas , Dietilnitrosamina/toxicidade , Fígado/efeitos dos fármacos , Malus , Animais , Biotransformação , Dano ao DNA , Fígado/enzimologia , Masculino , Ratos , Ratos Wistar
7.
J. physiol. biochem ; 70(4): 981-990, dic. 2014. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-131431

RESUMO

Lycopene is a carotenoid pigment produced by vegetables and fruits, with tomatoes and their processed products being the most abundant sources. A high number of conjugated dienes make lycopene a powerful radical scavenger. Its antioxidant properties are considered to be primarily involved in many beneficial health effects. The present study was designed to assess the protective effect of lycopene-enriched tomato paste against N-nitrosodiethylamine (NDEA)-induced oxidative stress in rats. Forty-eight male Wistar rats were divided randomly into six groups. Four groups were treated with tomato paste, per os, for 28 days in doses which were equivalent to 0.5 (groups II and V) and 2.5 mg/kg b.w./day of lycopene (groups III and VI). Rats from groups IV-VI were given intraperitoneally a single dose of NDEA, 150 mg/kg b.w. Group I (control) was given distilled water. Pretreatment with tomato paste protected the antioxidant enzymes: superoxide dismutase, catalase and glutathione reductase. Their activity was recovered by 32-97 %, as compared to NDEA-treated rats. Microsomal lipid peroxidation in the liver was decreased in rats pretreated with a lower dose of tomato paste by 28 %, as compared to animals given NDEA alone. Pretreatment with tomato paste caused a decrease in plasma concentration of protein carbonyls, even below the control level, in rats given NDEA. Moreover, a 10 % reduction of DNA damage in leucocytes caused by NDEA was observed. The tomato paste tested was able to suppress NDEA-induced oxidative stress in rats (AU)


Assuntos
Animais , Ratos , Antioxidantes/farmacocinética , Concentrados de Tomates , Estresse Oxidativo , Modelos Animais de Doenças , Substâncias Protetoras/farmacocinética , Peroxidação de Lipídeos , Ensaio Cometa/métodos , Carbonilação Proteica
8.
J Physiol Biochem ; 70(4): 981-90, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25387411

RESUMO

Lycopene is a carotenoid pigment produced by vegetables and fruits, with tomatoes and their processed products being the most abundant sources. A high number of conjugated dienes make lycopene a powerful radical scavenger. Its antioxidant properties are considered to be primarily involved in many beneficial health effects. The present study was designed to assess the protective effect of lycopene-enriched tomato paste against N-nitrosodiethylamine (NDEA)-induced oxidative stress in rats. Forty-eight male Wistar rats were divided randomly into six groups. Four groups were treated with tomato paste, per os, for 28 days in doses which were equivalent to 0.5 (groups II and V) and 2.5 mg/kg b.w./day of lycopene (groups III and VI). Rats from groups IV-VI were given intraperitoneally a single dose of NDEA, 150 mg/kg b.w. Group I (control) was given distilled water. Pretreatment with tomato paste protected the antioxidant enzymes: superoxide dismutase, catalase and glutathione reductase. Their activity was recovered by 32-97 %, as compared to NDEA-treated rats. Microsomal lipid peroxidation in the liver was decreased in rats pretreated with a lower dose of tomato paste by 28 %, as compared to animals given NDEA alone. Pretreatment with tomato paste caused a decrease in plasma concentration of protein carbonyls, even below the control level, in rats given NDEA. Moreover, a 10 % reduction of DNA damage in leucocytes caused by NDEA was observed. The tomato paste tested was able to suppress NDEA-induced oxidative stress in rats.


Assuntos
Antioxidantes/farmacologia , Carotenoides/farmacologia , Dietilnitrosamina/farmacologia , Lycopersicon esculentum/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Dano ao DNA , Avaliação Pré-Clínica de Medicamentos , Peroxidação de Lipídeos , Licopeno , Masculino , Ratos Wistar
9.
Drug Chem Toxicol ; 37(4): 472-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24580095

RESUMO

Apples abundant in phenolic compounds show a variety of biological activities that may contribute to health beneficial effects against cardiovascular diseases, diabetes, obesity and cancer. We investigated the effect of cloudy apple juice (CAJ) on the hepatic and mammary gland carcinogen metabolizing enzymes, DNA damage and liver injury, altered by 7,12-dimethylbenz[a]anthracene (DMBA). Sprague-Dawley female rats were gavaged with CAJ (10 ml/kg b.w.) for 28 consecutive days. DMBA was administered i.p. on the 27th and the 28th days. In the liver, feeding with CAJ decreased the activities of CYP1A1 and 1A2 and increased phase II enzymes. The activities of all enzymes tested were enhanced in the animals treated with DMBA alone and in combination with CAJ. The most significant changes in the level of the hepatic enzymes tested were observed for GST alpha and NQO1. In mammary gland CAJ induced an increase in the level of GST mu and GST pi, while DMBA and CAJ combined administration elevated GST pi only. This may be beneficial as GST pi is involved in the DMBA detoxification. Additionally, pretreatment with CAJ reduced the level of most of the blood biochemical liver and kidney markers elevated as a result of DMBA treatment. These findings indicate that CAJ may interfere with enzyme system involved in carcinogen metabolism. However, this effect seems to be dependent on tissue and carcinogen and is moderately effective in the case of DMBA. Moreover, CAJ can also provide some protection against the liver and kidney damage.


Assuntos
9,10-Dimetil-1,2-benzantraceno/toxicidade , Fígado/efeitos dos fármacos , Malus/química , Glândulas Mamárias Animais/efeitos dos fármacos , Animais , Bebidas , Carcinógenos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Dano ao DNA/efeitos dos fármacos , Feminino , Rim/efeitos dos fármacos , Rim/patologia , Fígado/enzimologia , Fígado/patologia , Glândulas Mamárias Animais/enzimologia , Ratos , Ratos Sprague-Dawley
10.
Phytother Res ; 28(1): 55-61, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23450834

RESUMO

UNLABELLED: Red beetroot contains a specific class of antioxidants collectively named betalains, which have been shown to have anticarcinogenic and anti-inflamatory potential. We investigated the effect of beetroot juice on the hepatic and mammary gland carcinogen metabolizing enzymes, DNA damage and liver injury, altered by 7,12-dimethylbenz[a]anthracene (DMBA). In the liver, pretreatment with beetroot juice significantly decreased levels and activities of the majority of tested biochemical parameters, elevated by DMBA. Feeding with beetroot juice decreased the activities of CYP1A1 and 1A2 and increased phase II enzymes. The activities of all enzymes tested were enhanced in the animals treated with DMBA alone and in combination with beetroot juice. The most significant changes in the level of the enzymes tested were observed for NAD(P)H: quinone oxidoreductase-1. In mammary gland, beetroot juice induced the level of glutathione S-transferase pi, enzyme involved in active metabolites of DMBA detoxification. The final effects of beetroot juice are tissue specific and depend on the class of carcinogen.


Assuntos
9,10-Dimetil-1,2-benzantraceno/efeitos adversos , Beta vulgaris/química , Fígado/efeitos dos fármacos , Glândulas Mamárias Animais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2 , Citocromos/metabolismo , Dano ao DNA , Feminino , Glutationa S-Transferase pi/metabolismo , Glutationa Transferase/metabolismo , Inativação Metabólica , Fígado/enzimologia , Fígado/patologia , Glândulas Mamárias Animais/enzimologia , Glândulas Mamárias Animais/patologia , NAD(P)H Desidrogenase (Quinona)/metabolismo , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley
11.
Phytother Res ; 27(8): 1214-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23042583

RESUMO

The aim of the study was to evaluate a protective effect of apple juice on KBrO3-induced oxidative stress in rats. Male Wistar rats were administered apple juice per os, 10 ml/kg b.w. for 28 days. On 27 day of the experiment, some rats were given i.p. a single 125 mg/kg b.w. dose of KBrO3 . Markers of oxidative damage and clinical chemistry parameters were determined. Treatment with apple juice prior to KBrO3 challenge prevented an increase in hepatic and renal microsomal lipid peroxidation by 25 and 44%, respectively, increased the activity of antioxidant enzymes in the liver by 29 - 59% and decreased the plasma content of carbonyl groups by 19%. Aminotransferases activity in plasma was reduced by 19% and 36%, concentrations of plasma bilirubin, cholesterol and creatinine were suppressed by 21%, 16% and 26%, respectively, in rats supplemented with juice before KBrO3 injection. No protective effect of apple juice on nuclear DNA was observed. Supplementation with cloudy apple juice to some extent attenuated oxidative damage induced by KBrO3 in the liver and kidney of rats as evidenced by alterations of certain oxidative stress markers and clinical chemistry parameters.


Assuntos
Bebidas , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Malus/química , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Biomarcadores/sangue , Bromatos/efeitos adversos , Rim/enzimologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/enzimologia , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Oxirredução , Ratos , Ratos Wistar
12.
Food Chem Toxicol ; 50(6): 2027-33, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22465004

RESUMO

Red beetroot, a common ingredient of diet, is a rich source of a specific class of antioxidants, betalains. Our previous studies have shown the protective role of beetroot juice against carcinogen induced oxidative stress in rats. The aim of this study was to examine the effect of long term feeding (28 days) with beetroot juice on phase I and phase II enzymes, DNA damage and liver injury induced by hepatocarcinogenic N-nitrosodiethylamine (NDEA). Long term feeding with beetroot juice decreased the activities of enzymatic markers of cytochrome P450, CYP1A1/1A2 and CYP2E1. NDEA treatment also reduced the activities of these enzymes, but increased the activity of CYP2B. Moreover, combined treatment with beetroot juice and NDEA enhanced significantly CYP2B only. Modulation of P450 enzyme activities was accompanied by changes in the relevant proteins levels. Increased level and activity of NQO1 was the most significant change among phase II enzymes. Beetroot juice reduced the DNA damage increased as the result of NDEA treatment, as well as the biomarkers of liver injury. Collectively, these results confirm the protective effect of beetroot juice against oxidative damage shown in our previous studies and indicate that metabolic alterations induced by beetroot feeding may protect against liver damage.


Assuntos
Alquilantes/antagonistas & inibidores , Alquilantes/toxicidade , Beta vulgaris/química , Bebidas , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Dietilnitrosamina/antagonistas & inibidores , Dietilnitrosamina/toxicidade , Animais , Western Blotting , Ensaio Cometa , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP2B1/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Citosol/metabolismo , Dano ao DNA , Eletroforese em Gel de Poliacrilamida , Glutationa Transferase/metabolismo , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , NADP/metabolismo , Proteínas/metabolismo , Ratos , Ratos Wistar
13.
Environ Toxicol Pharmacol ; 31(2): 339-46, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21787703

RESUMO

Chokeberry is a rich source of procyanidins known to have several types of biological activity including anticarcinogenic potential in experimental models. In this study we examined the effect of chokeberry juice on the hepatic and mammary gland carcinogen metabolizing enzyme expression altered by the polycyclic aromatic hydrocarbon, 7,12-dimethylbenz[a]anthracene (DMBA). Sprague-Dawley rats were gavaged with chokeberry juice (8 ml/kg b.w.) for 28 consecutive days. DMBA was administered i.p. on the 27th and the 28th days. Pretreatment with chokeberry juice reduced the activity of CYP1A1 and increased that of CYP2B involved in metabolic activation/detoxication of DMBA in rat liver, as well as expression and activity of phase II enzymes. Chokeberry juice had no effect on these parameters in the mammary gland and DMBA induced DNA damage in rat blood cells. These results together with our earlier observations indicate that metabolic alterations induced by chokeberry feeding are tissue specific and depend on the class of carcinogen.


Assuntos
9,10-Dimetil-1,2-benzantraceno/toxicidade , Carcinógenos/toxicidade , Frutas , Fígado/efeitos dos fármacos , Glândulas Mamárias Animais/efeitos dos fármacos , Photinia , Animais , Ensaio Cometa , Citocromo P-450 CYP1A1/biossíntese , Citocromo P-450 CYP2B1/biossíntese , Sistema Enzimático do Citocromo P-450/biossíntese , Dano ao DNA/efeitos dos fármacos , Feminino , Glutationa Transferase/biossíntese , Isoenzimas/biossíntese , Fígado/enzimologia , Glândulas Mamárias Animais/enzimologia , NAD(P)H Desidrogenase (Quinona)/biossíntese , Ratos , Ratos Sprague-Dawley
14.
Regul Toxicol Pharmacol ; 57(2-3): 266-73, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20347908

RESUMO

The aim of this study was to investigate cytotoxicity, acute and subchronic oral toxicity of an ionic liquid didecyldimethylammonium saccharinate [DDA][Sac] in rat. IC(50) values tested on six human cell lines varied from 1.44 microM to 5.47 microM. The compound tested was classified to the 4th toxicity class with a fixed LD(50) cut-off value 500 mg/kg. Organ pathology induced by [DDA][Sac] in an acute experiment included exfoliation of the surface layer of the colon and alveolar septa in lung parenchyma. In a subchronic experiment rats were administered 10, 30 and 100 mg/kg/day [DDA][Sac] for 28 days. Reduced body weight gain and slightly reduced food consumption was observed particularly in high-dose rats. Slight hematology changes were found only in mid-dose females. Statistically significant changes in clinical chemistry parameters included: increases in the ALT, SDH, ALP and GGT activities, and in glucose, blood urea nitrogen and creatinine concentrations. However, these changes did not occur in both sexes and were not dose-related with the exception of ALP in females. No treatment-related microscopic changes were observed in a subchronic experiment. Under the condition of this study the lowest-observed-adverse-effect level of [DDA][Sac] was considered to be 10 mg/kg/day.


Assuntos
Proliferação de Células/efeitos dos fármacos , Líquidos Iônicos/toxicidade , Compostos de Amônio Quaternário/toxicidade , Animais , Contagem de Células Sanguíneas , Peso Corporal/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sistema Digestório/efeitos dos fármacos , Sistema Digestório/patologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Concentração Inibidora 50 , Fígado/efeitos dos fármacos , Fígado/metabolismo , Testes de Função Hepática , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Especificidade de Órgãos , Ratos , Ratos Wistar , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica
15.
Drug Chem Toxicol ; 32(4): 395-404, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19793032

RESUMO

The aim of this study was to investigate acute and subacute oral toxicity of an ionic liquid, didecyldimethylammonium acesulfamate [DDA][Ace], in rats. The compound tested was classified to the fourth toxicity class with a fixed LD(50) cut-off value of 500 mg/kg. Organ pathology induced by [DDA][Ace] in acute experiments included exfoliation of the surface layer of the digestive tract and alveolar septa in lung parenchyma. In a subacute experiment, rats were administered 10, 50, and 100 mg/kg/day [DDA][Ace] for 28 days. Reduced body weight gain and reduced food consumption was observed in mid- and high-dose rats. Statistically significant hematology changes were found mostly in high-dose groups of both sexes: increases in hematocrit, mean corpuscular volume, and mean platelet volume. Statistically significant changes in clinical chemistry parameters included increases in the GGT, SDH, and LDH activity and bilirubin concentration, and decreases in triglycerides, glucose, and inorganic phosphorus concentration. No treatment-related microscopic changes were observed. Under the conditions of this study, the lowest-observed-adverse-effect level of [DDA][Ace] was considered to be 10 mg/kg/day.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Líquidos Iônicos/farmacologia , Ácido Oxônico/farmacologia , Administração Oral , Animais , Pressão Sanguínea/fisiologia , Relação Dose-Resposta a Droga , Ingestão de Alimentos , Feminino , Ratos , Ratos Sprague-Dawley , Ratos Wistar
16.
Int J Occup Med Environ Health ; 22(2): 115-23, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19617191

RESUMO

INTRODUCTION: The ethyl ether extract from Aquilegia vulgaris (L.) (Ranunculaceae) contains a lot of phenolic acids. Their hydroxyl groups are capable of donating hydrogen atoms at the initial stage of lipid peroxidation (LPO), which inactivates hydroxyperoxides formed from polyunsaturated fatty acids (PUFAs) and leads to breakdown of the propagation chain. MATERIAL AND METHODS: Rats pretreated with acetaminophen (APAP) (600 mg/kg b.w., p.o.) were given ethyl ether extract (100 mg/kg b.w., p.o.) obtained from A. vulgaris herb. The study parameters measured were microsomal lipid peroxidation, reduced glutathione, and the activity of hepatic antioxidant enzymes and some drug metabolizing enzymes. RESULTS: The treatment with ethyl ether extract of the herb produced a 87-95% decrease in uninduced and Fe2+/ascorbate-stimulated microsomal lipid peroxidation in the liver of rats receiving APAP. Hepatic glutathione level depleted by APAP increased significantly (by 18%) after the extract treatment. Antioxidant enzyme activity in the liver, inhibited by APAP, was found to increase after administration of the extract: catalase by about 36%, glutathione reductase by 27% and glutathione S-transferase by 29%. Glucose-6-phosphate dehydrogenase, which decreased after APAP administration, increased again by 26% after extract treatment. The extract tested did not affect the activity of DT-diaphorase. The cytochrome P450 content, depleted by APAP, increased as much as by 100% after the treatment. The activities of NADPH-cytochrome P450 reductase, aniline hydroxylase and aminopyrine N-demethylase were not affected. CONCLUSIONS: The protective effect of the Aquilegia vulgaris extract in APAP-induced liver injury was mediated by its antioxidant activity. The extract did not inhibit the formation of reactive intermediate metabolites of APAP.


Assuntos
Antioxidantes/metabolismo , Aquilegia , Microssomos Hepáticos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Análise de Variância , Animais , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Microssomos Hepáticos/metabolismo , Fitoterapia , Ratos , Ratos Wistar
17.
J Agric Food Chem ; 57(11): 5071-7, 2009 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-19378944

RESUMO

Chokeberry is a rich source of polyphenols, which may counteract the action of chemical carcinogens. The aim of this study was to examine the effect of chokeberry juice alone or in combination with N-nitrosodiethylamine (NDEA) on phase I and phase II enzymes and DNA damage in rat liver. The forced feeding with chokeberry juice alone decreased the activities of enzymatic markers of cytochrome P450, CYP1A1 and 1A2. NDEA treatment also decreased the activity of CYP2E1 but enhanced the activity of CYP2B. Pretreatment with chokeberry juice further reduced the activity of these enzymes. Modulation of P450 enzyme activities was accompanied by the changes in the relevant proteins levels. Phase II enzymes were increased in all groups of animals tested. Chokeberry juice augmented DNA damage and aggravated the effect of NDEA. These results indicate that chokeberry may protect against liver damage; however, in combination with chemical carcinogens it might enhance their effect.


Assuntos
Bebidas/análise , Carcinógenos/farmacocinética , Dietilnitrosamina/farmacocinética , Photinia/química , Extratos Vegetais/farmacologia , Animais , Biotransformação , Carcinógenos/toxicidade , Sistema Enzimático do Citocromo P-450/metabolismo , Dano ao DNA/efeitos dos fármacos , Dietilnitrosamina/toxicidade , Inativação Metabólica , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar
18.
Exp Toxicol Pathol ; 61(5): 443-51, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19059770

RESUMO

Six groups of male Wistar rats were treated as follows: in groups II, III and V liver damage was induced by CCl(4) (per os, 1590 mg/kg b.w.day) given 2 days a week for 6 weeks; group III was treated simultaneously with ethanol extract of Aquilegia vulgaris (100 mg/kg b.w.day) for 6 weeks; group V with silymarin, positive control, at a dose of 100 mg/kg b.w.day for 6 weeks; and groups IV and VI received only the extract or silymarin, respectively. Microsomal lipid peroxidation in the liver increased following CCl(4) treatment by 61-213% and was not changed significantly by the extract. The effect of silymarin was more pronounced, 19-52% decrease in the lipid peroxidation level. Hepatic glutathione was depleted by 22% in CCl(4)-treated rats. The extract tested did not change this parameter. The activity of antioxidant enzymes was significantly reduced after CCl(4) administration, by 42-63%. Co-administration of the extract or silymarin resulted in significant increase in these enzymes activity; however, the basal level was not reached. Hepatic hydroxyproline concentration was elevated over 5-fold in comparison with controls. Co-administration of the extract or silymarin decreased the level of hydroxyproline by 66% and 55%, respectively. Activity of serum hepatic enzymes was elevated in rats treated with CCl(4) by 47-8700%. Both the extract and silymarin reduced significantly these enzymes' activity. The extract caused a fall in bilirubin and cholesterol level in rats treated with CCl(4) by 42% and 17%, respectively. Histopathological examination revealed less-severe fibrosis in rats co-administered the extract or silymarin when compared to animals treated with CCl(4) alone.


Assuntos
Aquilegia/química , Tetracloreto de Carbono/toxicidade , Hepatopatias/prevenção & controle , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Animais , Doença Hepática Induzida por Substâncias e Drogas , Fibrose/induzido quimicamente , Fibrose/prevenção & controle , Glutationa/efeitos dos fármacos , Hidroxiprolina/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Hepatopatias/patologia , Masculino , Ratos , Ratos Wistar , Silimarina/farmacologia
19.
Indian J Exp Biol ; 45(8): 702-11, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17877147

RESUMO

The ethyl ether extract of A. vulgaris inhibited in vitro microsomal lipid peroxidation (IC50 58.8 microg/ml) and showed moderate ability to scavenge superoxide radicals and to chelate iron ions. The extract (100 mg/kg body weight, po) decreased uninduced and enzymatic microsomal lipid peroxidation in the liver of male rats pretreated with CCl4 (1 ml/kg body weight) by 27 and 40%, respectively. Activity of antioxidant and related enzymes (catalase and glucose-6-phosphate dehydrogenase) inhibited by CCl4 was significantly restored after administration of the extract. The extract itself significantly enhanced superoxide dismutase activity. There was no effect of the extract on hepatic glutathione level and cytochrome P450 content, both were decreased by CCl4. Neither CCl4 nor the tested extract affected activities of NADPH-cytochrome P450 reductase and two monooxygenases, aniline hydroxylase and aminopyrine n-demethylase. It can be concluded that the protective effect of the A. vulgaris extract in CCl4-induced liver injury is mediated by inhibition of microsomal lipid peroxidation and restoring activity of some antioxidant and related enzymes.


Assuntos
Aquilegia/química , Tetracloreto de Carbono/antagonistas & inibidores , Doença Hepática Induzida por Substâncias e Drogas , Depuradores de Radicais Livres/farmacologia , Hepatopatias/prevenção & controle , Animais , Tetracloreto de Carbono/toxicidade , Éter/química , Depuradores de Radicais Livres/uso terapêutico , Concentração Inibidora 50 , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos
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