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1.
Iran J Med Sci ; 46(5): 395-398, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34539014

RESUMO

In April 2018, a 20-year-old man with a history of methanol intoxication from an alcoholic drink two years ago, when he was 18 years old, was referred to Nikookari Eye Hospital in Tabriz, Iran. He was admitted to emergency service and underwent eight hours of hemodialysis at the time of poisoning. His past medical history was negative, and he did not take any medication after discharge. The patient had a driving license and never experienced any visual problems before. At presentation, his visual acuity was 160/200 in both eyes with the main complaint of visual field deterioration. Other neurologic exams and brain magnetic resonance imaging (MRI) were reported normal by a neurologist. Optic disc cupping was near total in both eyes with a very narrow remaining rim. Optic disc cupping was very similar to glaucomatous cupping. Intraocular pressure was checked several times via Goldmann tonometry and was 13 mmHg. There was no history of refractive surgery leading to thin cornea. Based on this case, methanol poisoning can mimic glaucomatous optic disc cupping. This is the first case report of methanol toxicity-related optic disc cupping from Iran.


Assuntos
Metanol/toxicidade , Disco Óptico/efeitos dos fármacos , Humanos , Irã (Geográfico) , Masculino , Metanol/efeitos adversos , Disco Óptico/fisiopatologia , Tonometria Ocular/métodos , Adulto Jovem
2.
Environ Sci Pollut Res Int ; 26(8): 7711-7717, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30671757

RESUMO

Many researchers have focused on controlling pest insects and vectors by natural products because of their low environmental pollution. The present study was conducted to evaluate the antioxidant and larvicidal activities of chloroform and methanol extracts of the leaves, fruits, roots, and isolated coumarin compounds (prantschimgin, oxypeucedanin, and 6-hydroxymethylherniarin) of Ferulago trifida from the Apiaceae family against Anopheles stephensi as one of the main malaria vectors. For insecticidal evaluation, A. stephensi larvae were exposed to different concentrations of the extracts and pure compounds (0.625-1280 ppm) according to the WHO protocol. The mortality percentages were measured 24 h after treatment and lethal concentration values were calculated. In addition, radical scavenging activities of the mentioned extracts and compounds were measured by the DPPH method. The methanol extract of fruits showed potent insecticidal properties with LC50 and LC90 values of 2.94 and 18.12 ppm, respectively. The chloroform extracts of the fruits and leaves were the second and third extracts with larvicidal effects. Among pure compounds, only oxypeucedanin showed moderate toxicity against A. stephensi with LC50 and LC90 values of 116.54 and 346.41 ppm, respectively. The antioxidant activities of the methanol extracts of leaves and fruits were stronger than other extracts with IC50 values of 155.83 and 159.32 ppm, respectively. In conclusion, the methanol extract of F. trifida fruits can be used as a potent bio-insecticide in green control programs of mosquitoes, especially A. stephensi.


Assuntos
Anopheles/efeitos dos fármacos , Inseticidas/toxicidade , Metanol/toxicidade , Mosquitos Vetores , Aedes , Animais , Anopheles/fisiologia , Apiaceae , Culex , Frutas , Larva , Dose Letal Mediana , Malária , Extratos Vegetais , Folhas de Planta , Testes de Toxicidade
3.
CNS Neurol Disord Drug Targets ; 17(7): 528-538, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29968547

RESUMO

BACKGROUND & OBJECTIVE: The adolescent brain has a higher vulnerability to alcoholinduced neurotoxicity, compared to adult's brain. Most studies have investigated the effect of ethanol consumption on the body, however, methanol consumption, which peaked in the last years, is still poorly explored. METHOD: In this study, we investigated the effects of methanol neurotoxicity on memory function and pathological outcomes in the hippocampus of adolescent rats and examined the efficacy of Light- Emitting Diode (LED) therapy. Methanol induced neurotoxic rats showed a significant decrease in the latency period, in comparison to controls, which was significantly improved in LED treated rats at 7, 14 and 28 days, indicating recovery of memory function. In addition, methanol neurotoxicity in hippocampus caused a significant increase in cell death (caspase3+ cells) and cell edema at 7 and 28 days, which were significantly decreased by LED therapy. Furthermore, the number of glial fibrillary acid protein astrocytes was significantly lower in methanol rats, compared to controls, whereas LED treatment caused their significant increase. Finally, methanol neurotoxicity caused a significant decrease in the number of brain-derived neurotrophic factor (BDNF+) cells, but also circulating serum BDNF, at 7 and 28 days, compared to controls, which were significantly increased by LED therapy. Importantly, LED significantly increased the number of Ki-67+ cells and BDNF levels in the serum and hypothalamus in control-LED rats, compared to controls without LED therapy. CONCLUSION: In conclusion, chronic methanol administration caused severe memory impairments and several pathological outcomes in the hippocampus of adolescent rats which were improved by LED therapy.


Assuntos
Apoptose/efeitos dos fármacos , Hipocampo/patologia , Transtornos da Memória , Metanol/toxicidade , Fototerapia/métodos , Solventes/toxicidade , Animais , Apoptose/efeitos da radiação , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/efeitos da radiação , Edema Encefálico/induzido quimicamente , Edema Encefálico/terapia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/efeitos da radiação , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/patologia , Transtornos da Memória/terapia , Ratos , Ratos Wistar , Fatores de Tempo
4.
Adv Exp Med Biol ; 854: 437-41, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26427443

RESUMO

Evidence is growing that exposure of tissue to low energy photon irradiation in the far-red (FR) to near-infrared (NIR) range of the spectrum, collectively termed "photobiomodulation" (PBM) can restore the function of damaged mitochondria, upregulate the production of cytoprotective factors and prevent apoptotic cell death. PBM has been applied clinically in the treatment of soft tissue injuries and acceleration of wound healing for more than 40 years. Recent studies have demonstrated that FR/NIR photons penetrate diseased tissues including the retina. The therapeutic effects of PBM have been hypothesized to result from intracellular signaling pathways triggered when FR/NIR photons are absorbed by the mitochondrial photoacceptor molecule, cytochrome c oxidase, culminating in improved mitochondrial energy metabolism, increased cytoprotective factor production and cell survival. Investigations in rodent models of methanol-induced ocular toxicity, light damage, retinitis pigmentosa and age-related macular degeneration have demonstrated the PBM attenuates photoreceptor cell death, protects retinal function and exerts anti-inflammatory actions.


Assuntos
Raios Infravermelhos , Fototerapia/métodos , Retina/efeitos da radiação , Doenças Retinianas/terapia , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Modelos Animais de Doenças , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Eletrorretinografia , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/efeitos da radiação , Humanos , Metanol/toxicidade , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação , Fótons , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Células Fotorreceptoras de Vertebrados/efeitos da radiação , Ratos , Retina/efeitos dos fármacos , Retina/patologia , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/fisiopatologia
5.
J Ethnopharmacol ; 174: 287-92, 2015 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-26303017

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The two species of Filipendula genus, Filipendula hexapetala Gilib. and Filipendula ulmaria (L.) Maxim are a traditional herbal medicine widely used to treat haemorrhoids, diarrhoea, fever, rheumatism and arthritic pain, kidney problems, to stop bleeding, and the common cold, as well as food supplements. However, no scientific study has been performed to validate genotoxic and/or antigenotoxic potentials of these two Filipendula species. AIM OF THE STUDY: The aim of the present study was to examine the genotoxic and possible in vitro and in vivo DNA protection potential of methanol extracts of F. hexapetala and F. ulmaria. MATERIALS AND METHODS: The genotoxicity of different concentrations of F. hexapetala and F. ulmaria methanol extracts from roots and aerial parts (20, 40 and 80 mg/ml), mixed with standard food for Drosophila, was evaluated in vivo in the anterior midgut of Drosophila melanogaster using a modified alkaline comet assay. The protective effects of the highest dose of extracts were observed in somatic cells of third-instar larvae against ethyl methanesulphonate (EMS)-induced genotoxicity. Also, DNA protection activity of methanol extracts from F. hexapetala and F. ulmaria (100, 200, and 400 µg/ml) against hydroxyl radical-induced DNA damage was determined under in vitro conditions. RESULTS: The results showed that methanol extracts from the root and aerial part of F. hexapetala at a concentration of 20mg/ml indicated the absence of genotoxicity. Also, there were no statistically significant differences in total scores between any of the groups treated with F. ulmaria root extract and the negative control group, while F. ulmaria aerial part extract possess weak genotoxic effects depending on the concentrations. The percentage reduction in DNA damage was more evident in the group of larvae simultaneously treated with EMS and the highest dose of F. hexapetala root or aerial part extracts and F. ulmaria root extract (91.02, 80.21, and 87.5%, respectively) and less expressive in the group simultaneously treated with F. ulmaria aerial part extract (54.7%). F. hexapetala root and aerial part extracts and F. ulmaria root extract possess strong capabilities to protect DNA from being damaged by hydroxyl radicals. CONCLUSIONS: It can be concluded that F. hexapetala root and aerial part extracts and F. ulmaria root extract demonstrated the absence of genotoxic activity. The extracts appeared to have antigenotoxic effect, reducing the levels of DNA damage induced by EMS by more than 80%. Also, F. hexapetala root and aerial part extracts and F. ulmaria root extracts could effectively protect against hydroxyl radical-induced DNA damage.


Assuntos
Filipendula , Metanol/toxicidade , Componentes Aéreos da Planta/toxicidade , Extratos Vegetais/toxicidade , Raízes de Plantas/toxicidade , Animais , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/fisiologia , Drosophila melanogaster , Testes de Mutagenicidade/métodos , Extratos Vegetais/isolamento & purificação
6.
Niger J Physiol Sci ; 29(2): 107-11, 2014 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-26196575

RESUMO

The study was conducted to investigate safety associated with prolonged consumption of Moringa oleifera leaves as beverage. Fourteen rats were used in this study. They were divided into 2 groups each containing 7 rats. Rats in group I received 2ml/kg of corn oil (standard vehicle drug). Animals in groups II were administered with 400mg/kg body of methanolic extract of Moringa oleifera (MEMO) for five weeks respectively. Serum collected was analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, globulin, blood urea nitrogen (BUN) and creatinine. There was significant (P<0.05) decrease in serum total protein, albumin, globulin and AST activity. The activity of ALT decreased but not significant. Similarly, 400mg/kg body of MEMO led to significant (P<0.05) decrease in serum BUN and creatinine. All experimental animals that received 400mg/kb of MEMO had significant (P<0.05) decrease in body weight from week to week 4 of the experiment. Taken together, 400mg/kg body of MEMO seemed to be toxic to the liver with apparently no toxicity in the kidney. Hence, prolonged exposure is not advisable as such could portend danger to the liver.


Assuntos
Rim/metabolismo , Fígado/metabolismo , Metanol/administração & dosagem , Moringa oleifera , Extratos Vegetais/administração & dosagem , Animais , Esquema de Medicação , Feminino , Rim/química , Rim/efeitos dos fármacos , Fígado/química , Fígado/efeitos dos fármacos , Metanol/toxicidade , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Folhas de Planta , Ratos , Ratos Wistar
7.
J Neuroophthalmol ; 32(4): 325-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22810212

RESUMO

BACKGROUND: To present the effect of erythropoietin for the treatment of methanol optic neuropathy. METHODS: Two patients with methanol optic neuropathy were treated with 10,000 IU of intravenous erythropoietin twice a day for 3 days, 500 mg of methylprednisolone twice a day for 5 days (followed by 2 weeks of oral prednisolone [1 mg/kg per day]), and daily doses of vitamin B12, vitamin B6, and folic acid for 1 month. RESULTS: At presentation, the patients had no perception of light in both eyes, associated with mildly swollen optic discs. Both responded dramatically to the treatment regimen. In the first patient, visual acuity improved to 20/20 in both eyes within 3 days, whereas in the second patient, visual acuity returned to counting fingers at 6 feet, right eye, and 20/30, left eye, within 3 weeks. CONCLUSION: Intravenous erythropoietin may be an effective adjuvant when combined with current treatment for patients with methanol optic neuropathy.


Assuntos
Eritropoetina/uso terapêutico , Metanol/toxicidade , Doenças do Nervo Óptico/induzido quimicamente , Doenças do Nervo Óptico/tratamento farmacológico , Solventes/toxicidade , Administração Intravenosa , Administração Oral , Adulto , Anti-Inflamatórios/administração & dosagem , Humanos , Masculino , Metilprednisolona/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Disco Óptico/patologia , Prednisolona/administração & dosagem , Tomografia de Coerência Óptica , Testes de Campo Visual
8.
J Med Assoc Thai ; 95 Suppl 4: S76-81, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22696856

RESUMO

BACKGROUND: The retinal pathophysiology of methanol intoxication is that formate inhibits retinal mitochondrial function and increases oxidative stress. OBJECTIVE: To investigate the effect of coenzyme Q10 and curcumin on chronic methanol intoxication causing retinopathy in rats. MATERIAL AND METHOD: The authors designed an experimental study of chronic methanol intoxication in rats depleted of folate with methotrexate. The studied group received methanol (2 mg/kg body weight in saline by intraperitoneal injection) and methotrexate (0.1 mg/kg body weight in saline by subcutaneous injection) every other day for ten weeks to induce chronic methanol intoxication, while another group received saline as vehicle and served as control group. The studied rats were confirmed to develop significant retinopathy after 10 weeks and then assigned to three treatment arms: either corn oil (as control) or coenzyme Q10 (20 mg/kg/day) or Curcuma longa extract (2.5 mg/kg/day) for four weeks. Eyes were enucleated and the retinal tissue was prepared for histological examination. The sections were evaluated by an experienced pathologist and blinded to the experimental conditions. RESULTS: Histological analysis revealed that animals treated with both methanol and methotrexate showed vacuolation of photoreceptor inner segment and disaggregation of cells in the inner and outer nuclear layers of the retina compared to a normal histological appearance in control animals. The retinal histology in the experimental animals with administration of Coenzyme Q10 or Curcuma longa extract appeared essentially normal and this was not found in the experimental animals which received corn oil. CONCLUSION: Coenzyme Q10 and curcumin administration improves retinal histology by reversing the pathological changes due to chronic methanol and establish a morphologically normal retina.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Curcumina/uso terapêutico , Metanol/toxicidade , Doenças Retinianas/tratamento farmacológico , Ubiquinona/análogos & derivados , Vitaminas/uso terapêutico , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Doenças Retinianas/induzido quimicamente , Solventes/toxicidade , Ubiquinona/uso terapêutico
9.
Toxicol Ind Health ; 28(6): 549-59, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21937533

RESUMO

Methanol is primarily metabolized by oxidation to formaldehyde and then to formate. These processes are accompanied by formation of superoxide anion and hydrogen peroxide. This article reports data on the effect of methanol-induced oxidative damage in experimental rats and the role of aqueous extract of Opuntia vulgaris fruit extract (OE) to counteract the toxicity induced by methanol. The animals were exposed to methanol at a dose of 2.37 g/kg body weight intraperitoneally for 30 days. OE was found to contain large amounts of polyphenols and carotenoids and significant antioxidant capacities highlighted by scavenging activities for 2,2-diphenyl-l-picrylhydrazyl. The treatment with methanol exhibited a significant increase in serum hepatic and renal biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, bilirubin, urea, and creatinine). Methanol intoxication significantly increased hepatic and renal lipid peroxidation evaluated by thiobarbituric acid reactive substances in treated rats as compared to controls. However, hepatic and renal antioxidant enzymes namely superoxide dismutase, catalase, and glutathione peroxidase were significantly decreased in methanol-treated animals as compared to controls. The results concluded that treatment with OE prior to methanol intoxication has significant role in protecting animals from methanol-induced hepatic and renal histopathological and oxidative damage.


Assuntos
Sequestradores de Radicais Livres/farmacologia , Metanol/toxicidade , Opuntia/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Análise de Variância , Animais , Biomarcadores/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Flavonoides/análise , Flavonoides/farmacologia , Sequestradores de Radicais Livres/química , Frutas/química , Histocitoquímica , Injeções Intraperitoneais , Rim/química , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Metanol/administração & dosagem , Fenóis/análise , Fenóis/farmacologia , Extratos Vegetais/química , Ratos , Ratos Wistar
10.
Hum Exp Toxicol ; 30(12): 1963-71, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21422078

RESUMO

The ameliorative effects of Opuntia vulgaris fruit extract (OE) were evaluated against methanol-induced haematological and biochemical toxicity in rats. The methanol-induced haematological and biochemical perturbation significantly decreased the levels of red blood cell (RBC), haemoglobin (Hb), haematocrit (Ht), serum total protein and increased glucose, cholesterol, and triglyceride levels in serum. Treatment of rats with methanol significantly increased lipid peroxidation (LPO) level and decreased the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in erythrocytes. OE treatment could increase significantly the levels of RBC, Hb, Ht and total protein, and decrease glucose, cholesterol and triglyceride levels in serum, and increase the activities of SOD, CAT and GPx in erythrocytes, when compared with methanol-treated group. Spleen histopathology showed that OE could significantly reduce the incidence of spleen lesion induced by methanol. These results suggested that OE could exhibit a potential source of natural antioxidants against methanol-induced haematological and biochemical disruption in rats. The protective effects of OE may be due to the modulation of antioxidant enzymes activities and inhibition of LPO.


Assuntos
Antioxidantes/toxicidade , Doenças Hematológicas/tratamento farmacológico , Metanol/toxicidade , Opuntia/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Solventes/toxicidade , Animais , Análise Química do Sangue , Eritrócitos/efeitos dos fármacos , Eritrócitos/patologia , Frutas/química , Doenças Hematológicas/induzido quimicamente , Doenças Hematológicas/metabolismo , Testes Hematológicos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Oxirredutases/metabolismo , Ratos , Ratos Wistar , Baço/efeitos dos fármacos , Baço/patologia , Esplenopatias/induzido quimicamente , Esplenopatias/patologia
11.
Ukr Biokhim Zh (1999) ; 83(5): 67-81, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22276430

RESUMO

The Hansenula polymorpha GSH1/MET1 gene was cloned by complementation of glutathione-dependent growth of H. polymorpha gsh1 mutant isolated previously as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) resistant and cadmium ion sensitive clone. The H. polymorpha GSH1 gene was capable of restoring cadmium ion resistance, MNNG sensitivity, normal glutathione level and cell proliferation on minimal media without addition of cysteine or glutathione, when introduced into the gsh1 mutant cells. It was shown that the H. polymorpha GSH1 gene has homology to the Saccharomyces cerevisiae MET1 gene encoding S-adenosyl-L-methionine uroporphyrinogen III transmethylase, responsible for the biosynthesis of sulfite reductase cofactor, sirohaem. The H. polymorpha GSH1/MET1 gene deletion cassette (Hpgsh1/met1::ScLEU2) was constructed and corresponding null mutants were isolated. Crossing data of the point gsh1 and null gsh1/met1 mutants demonstrated that both alleles were located to the same gene. The null gsh1/met1 mutant showed total growth restoration on minimal media supplemented with cysteine or glutathione as a sole sulfur source, but not with inorganic (sulfate, sulfite) or organic (methionine, S-adenosylmethionine) sources of sulfur. Moreover, both the point gsh1 and null gsh1/met1 mutants displayed increased sensitivity to the toxic carbon substrate methanol, formaldehyde, organic peroxide and cadmium ions.


Assuntos
Cisteína/metabolismo , Glutamato-Cisteína Ligase/metabolismo , Glutationa/metabolismo , Metiltransferases/metabolismo , Pichia/genética , Proteômica/métodos , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Sequência de Aminoácidos , Cádmio/metabolismo , Cádmio/toxicidade , Clonagem Molecular , Deleção de Genes , Expressão Gênica/efeitos dos fármacos , Teste de Complementação Genética , Glutamato-Cisteína Ligase/química , Metanol/metabolismo , Metanol/toxicidade , Metilnitronitrosoguanidina/toxicidade , Metiltransferases/química , Dados de Sequência Molecular , Pichia/efeitos dos fármacos , Pichia/enzimologia , S-Adenosilmetionina/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/enzimologia , Proteínas de Saccharomyces cerevisiae/química , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Sulfatos/metabolismo , Sulfatos/farmacologia , Ésteres do Ácido Sulfúrico/metabolismo , Ésteres do Ácido Sulfúrico/farmacologia
12.
J Med Food ; 13(4): 985-91, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20482279

RESUMO

Lycopene is one of the major carotenoids and is found almost exclusively in tomatoes and tomato products. This study was performed to evaluate the effect of lycopene on methanol-induced liver injury and to compare the results with those after fomepizole, which is used in treatment of methanol intoxication. Experiments were carried out with 30 female Wistar rats weighting 180-200 g. Rats were injected with a intraperitoneally dose of 3 g/kg methanol as a 50% solution in isotonic saline once for intoxication. Rats were pretreated with fomepizole (50 mg/kg) and/or lycopene (10 mg/kg) before methanol. After 24 hours all the drug-treated and intoxicated rats were sacrificed under anesthesia. Malondialdehyde (MDA) levels were determined in order to assess lipid peroxidation, and caspase-3 activity was determined by immunostaining of liver tissues to evaluate apoptosis. Methanol administration significantly increased the MDA level and caspase-3 activity in liver. Pretreatment with lycopene and/or fomepizole decreased the MDA levels significantly. Similarly, lycopene and fomepizole decreased methanol-induced caspase-3 activity. The findings of the present study demonstrate that methanol intoxication causes hepatic toxicity in rats and that this is likely a result of reactive oxygen species and apoptosis induction. Lycopene has protective effects against methanol-induced hepatic injury similar to fomepizole. It was demonstrated for the first time that both lycopene and fomepizole prevent methanol-induced hepatic injury by reducing the increase of lipid oxidation and caspase-3 activation.


Assuntos
Carotenoides/uso terapêutico , Caspase 3/metabolismo , Ativação Enzimática/efeitos dos fármacos , Hepatopatias Alcoólicas/tratamento farmacológico , Fígado/enzimologia , Metanol/toxicidade , Pirazóis/uso terapêutico , Animais , Modelos Animais de Doenças , Feminino , Fomepizol , Humanos , Fígado/efeitos dos fármacos , Hepatopatias Alcoólicas/enzimologia , Hepatopatias Alcoólicas/metabolismo , Licopeno , Malondialdeído/metabolismo , Metanol/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar
13.
J Ethnopharmacol ; 127(2): 286-91, 2010 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-19914367

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The manuscript is one of the series of attempts in authenticating scientific documentation of the seeds of Carica papaya being traditionally used for contraception. AIMS OF THE STUDY: To establish safety of the methanol sub-fraction (MSF) of the seeds of Carica papaya as a male contraceptive following long term oral treatment. MATERIALS AND METHODS: MSF was administered orally to albino rats at multiples of contraceptive dose (CD) at 50 (1x), 100 (2x), 250 (5x) and 500 (10x)mg/kg body weight daily for 52 weeks. Body weight, organs weight, morbidity, mortality, clinical chemistry, sperm analysis, histopathology and serum testosterone were evaluated to assess the safety and contraceptive efficacy. RESULTS: MSF treatment at various dose regimens, daily for 52 weeks did not show significant changes in body weight, organs weight, food and water intake and pre-terminal deaths compared to those of control animals. Sperm count and viability in 50mg/kg body weight treated animals and the weight of epididymis, seminal vesicle and prostate of all the treated animals showed significant reduction compared to control. Cauda epididymal spermatozoa of 50mg/kg body weight treated animals were immotile. Azoospermia was observed in 100, 250 and 500 mg/kg body weight treated animals. Serum clinical parameters, serum testosterone and histopathology of vital organs were comparable to those of control animals. Histology of testis revealed adverse effects on the process of spermatogenesis, while the histology of epididymis, seminal vesicles and ventral prostate showed no changes compared to control. CONCLUSION: The long term daily oral administration of MSF affects sperm parameters without adverse side effects and is clinically safe as a male contraceptive.


Assuntos
Carica , Anticoncepcionais Masculinos/administração & dosagem , Anticoncepcionais Masculinos/toxicidade , Metanol/administração & dosagem , Metanol/toxicidade , Extratos Vegetais/administração & dosagem , Extratos Vegetais/toxicidade , Sementes , Administração Oral , Animais , Anticoncepcionais Masculinos/isolamento & purificação , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Masculino , Extratos Vegetais/isolamento & purificação , Ratos , Ratos Wistar , Espermatogênese/efeitos dos fármacos , Espermatogênese/fisiologia , Testículo/efeitos dos fármacos , Testículo/patologia , Fatores de Tempo
14.
Int. j. morphol ; 25(3): 609-614, Sept. 2007. ilus, tab
Artigo em Inglês | LILACS | ID: lil-626912

RESUMO

Effects of graded dosages of methanolic extract of Aspilia Africana were examined on the estrous cycle, uterine weights and histology to determine its effects on the reproductive functions of 25 cyclic female rats. The rats were randomized into five groups A, B, C, D, and E. They were given Omg/kg body weight, 150 mg/kg body weight, 200 mg/kg body weight, 250 mg/kg body weight, and 300 mg/kg body weight, respectively. The effect on the estrous cycle was determined by vaginal lavage while routine histological preparations were done with haematoxylin-eosin stains. All values were statistically compared at appropriate confidence intervals. Estrous cycles were significantly reduced in a dose-dependent manner and histology revealed a dose-dependent toxicity.


Se examinaron los efectos de las distintas dosificaciones de extracto de metanol de Aspilia africana, en los ciclos estrales, peso uterino y en la histología para determinar sus efectos en las funciones reproductivas de 25 ratas hembra. Las ratas fueron randomizadas en cinco grupos: A, B, C, D y E y recibieron 0 mg/kg de peso corporal, 150 mg/kg de peso corporal, 200 mg/kg de peso corporal, 250 mg/kg de peso corporal y 300 mg/kg de peso corporal respectivamente. El efecto en el ciclo estral fue determinado por frotis vaginal, preparado con técnicas histológicas de rutina y teñido con hematoxilina-eosina. Todos los valores fueron estadísticamente comparados con intervalos de confianza adecuados. Los ciclos estrales fueron significativamente reducidos en forma dosis dependiente y la histología reveló una toxicidad dosis dependiente.


Assuntos
Animais , Feminino , Ratos , Útero/efeitos dos fármacos , Extratos Vegetais/toxicidade , Asteraceae , Ciclo Estral/efeitos dos fármacos , Metanol/toxicidade , Reprodução/efeitos dos fármacos , Útero/patologia , Peso Corporal/efeitos dos fármacos , Ratos Wistar , Folhas de Planta
15.
Exp Toxicol Pathol ; 57(5-6): 427-35, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16616465

RESUMO

The study aimed to evaluate the effect of L-carnitine on hepatic cytochrome P450-dependent monooxygenases exposed to methanol. Male Spraque-Dawley rats were given methanol (1/4 LD50 and 1/2 LD50) together with L-carnitine (1g/kg body weight). The parameters of microsome electron transport chains I and II and the levels of CYP2E1, CYP2B1/2 and CYP1A2 were measured 8, 12, 24, 48, 72 and 96 h after exposure. L-carnitine did not affect cytochrome P450 but it significantly increased at 72 and 96 h NADPH-cytochrome P450 reductase. It stimulated cytochrome b5 at 48 and 96 h and NADH-cytochrome b5 reductase activity at 12, 72 and 96 h. Methanol, especially the lower dose, inhibited cytochrome P450 after 48 h, but the higher methanol dose inhibited NADH-cytochrome b5 reductase activity in this time. L-carnitine, combined with the lower dose of methanol, stimulated NADPH-cytochrome P450 reductase after 48 h and cytochrome b5 and NADH-cytochrome b5 reductase over the whole period of observation. L-carnitine stimulated CYP2B1/2 but not CYP2E1 and CYP1A2. Methanol stimulated CYP2E1 at 24 h, but CYP1A2 at 96 h in the studied doses. CYP2B1/2 was induced by the lower dose of methanol at 24 h but by the higher one at 96 h. When given together, L-carnitine and methanol (1/2 LD50) significantly stimulated CYP2E1 up to 170% at 24 h and 145% at 96 h.


Assuntos
Hidrocarboneto de Aril Hidroxilases/biossíntese , Carnitina/uso terapêutico , Metanol/toxicidade , Microssomos Hepáticos/efeitos dos fármacos , Solventes/toxicidade , Complexo Vitamínico B/uso terapêutico , Administração Oral , Animais , Relação Dose-Resposta a Droga , Interações Medicamentosas , Indução Enzimática , Injeções Intraperitoneais , Masculino , Microssomos Hepáticos/enzimologia , NADPH-Ferri-Hemoproteína Redutase/biossíntese , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
16.
Arch Toxicol ; 79(10): 571-81, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15889238

RESUMO

The effect of methanol on the levels of endogenous carnitine and its derivatives was studied in male Sprague-Dawley rats aged three months. In addition, the effect of L-carnitine supplementation on metabolic disturbances caused by methanol intoxication was studied. The rats were randomized into six groups, including two control groups. Methanol was given at 1/4 LD(50) and 1/2 LD(50)/kg b.w. (or water in control) through an intragastric tube, and L-carnitine (or 0.9% NaCl in the control) was injected intraperitoneally. The levels of plasma L-carnitine and its derivatives were measured at selected time points for four days. Following methanol administration, the rats exhibited dose-dependent increases in L-carnitine levels and altered ratios of L-carnitine and its derivatives. L-carnitine supplementation accelerated the normalization of metabolic disturbances, as indicated by the acylcarnitine to free carnitine ratio (AC/FC). The protective effect of L-carnitine is supported by the fact that 100% of the methanol-treated rats supplemented with carnitine survived, while 8/60 rats and 27/101 rats died at methanol doses of 1/4 LD(50) and 1/2 LD(50), respectively, in groups without L-carnitine supplementation.


Assuntos
Intoxicação Alcoólica/sangue , Carnitina/análogos & derivados , Metanol/toxicidade , Intoxicação Alcoólica/metabolismo , Intoxicação Alcoólica/prevenção & controle , Animais , Área Sob a Curva , Carnitina/administração & dosagem , Carnitina/sangue , Carnitina/farmacocinética , Relação Dose-Resposta a Droga , Meia-Vida , Dose Letal Mediana , Masculino , Taxa de Depuração Metabólica , Metanol/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Análise de Sobrevida
17.
Horiz. méd. (Impresa) ; 3(1/2): 69-78, dic. 2003. ilus, tab, graf
Artigo em Espanhol | LILACS, LIPECS | ID: lil-677693

RESUMO

Se realizó el estudio fitoquímico, toxicológico agudo y citotóxico del cinnamomum zeylanicum (canela). Para la determinación de la DL50 se utilizaron 30 ratones albinos, cuyos pesos oscilaron entre 25 y 30 gr., siguiendo el método de Probits. Igualmente se determinó la concentración letal media (CL-50) en artemia salina. La actividad citotóxica y teratogénica fue evaluada en huevos de Tetrapygus Níger (erizo de mar). Nos permite concluir, siguiendo los criterios de William, que el extracto metanólico de la canela es ligeramente tóxico y posee efecto citotóxico frente al erizo de mar, no evidenciándose efecto teratogénico, a las dosis empleadas.


We have performed a Phytochemic. Toxicologic and Cytotoxic study, of Cinamomum zeylanicum (canela) in laboratory. We have determinated the letal 50-doses (DLSO) in mice, the letal middle concentration (CL_50) in Artemia salina and the cytotoxic and teratogenic effect on Tetrapygus niger eggs (sea Hedgehog). We may conclude following the William Criterions that the metanolic extract of canela is lightly toxic and it has cytotoxic effects on sea Hedgehog at the doses studied.


Assuntos
Masculino , Animais , Feminino , Camundongos , Artemia , Cinnamomum zeylanicum/toxicidade , Citotoxinas , Ouriços-do-Mar , Extratos Vegetais/toxicidade , Metanol/toxicidade , Testes de Toxicidade/métodos
18.
Proc Natl Acad Sci U S A ; 100(6): 3439-44, 2003 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-12626762

RESUMO

Methanol intoxication produces toxic injury to the retina and optic nerve, resulting in blindness. The toxic metabolite in methanol intoxication is formic acid, a mitochondrial toxin known to inhibit the essential mitochondrial enzyme, cytochrome oxidase. Photobiomodulation by red to near-IR radiation has been demonstrated to enhance mitochondrial activity and promote cell survival in vitro by stimulation of cytochrome oxidase activity. The present studies were undertaken to test the hypothesis that exposure to monochromatic red radiation from light-emitting diode (LED) arrays would protect the retina against the toxic actions of methanol-derived formic acid in a rodent model of methanol toxicity. Using the electroretinogram as a sensitive indicator of retinal function, we demonstrated that three brief (2 min, 24 s) 670-nm LED treatments (4 J/cm(2)), delivered at 5, 25, and 50 h of methanol intoxication, attenuated the retinotoxic effects of methanol-derived formate. Our studies document a significant recovery of rod- and cone-mediated function in LED-treated, methanol-intoxicated rats. We further show that LED treatment protected the retina from the histopathologic changes induced by methanol-derived formate. These findings provide a link between the actions of monochromatic red to near-IR light on mitochondrial oxidative metabolism in vitro and retinoprotection in vivo. They also suggest that photobiomodulation may enhance recovery from retinal injury and other ocular diseases in which mitochondrial dysfunction is postulated to play a role.


Assuntos
Metanol/toxicidade , Fototerapia , Retina/efeitos dos fármacos , Retina/lesões , Animais , Eletrorretinografia , Formiatos/metabolismo , Formiatos/toxicidade , Raios Infravermelhos/uso terapêutico , Masculino , Microscopia Eletrônica , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação , Ratos , Ratos Long-Evans , Retina/fisiopatologia
19.
Patol Fiziol Eksp Ter ; (3): 17-9, 2000.
Artigo em Russo | MEDLINE | ID: mdl-10983474

RESUMO

The response of hematological system, carbohydrate metabolism and pathomorphologic alterations in the viscera were studied for four weeks on the model of chronic alcoholization in conditions of hydrolytic alcohol production. It is shown that maximal deviations of all the parameters in white conventional rats occur after receiving a combined ethanol dose in inhalation of a mixture of methanol and furfurol vapour. Less manifest pathology was revealed in simultaneous introduction of nootropil solution. Thus, functional-morphologic changes in alcoholic intoxication in unfavourable environment are reversible in purposeful application of drugs with neurometabolic effect.


Assuntos
Alcoolismo/fisiopatologia , Nootrópicos/uso terapêutico , Piracetam/uso terapêutico , Alcoolismo/sangue , Alcoolismo/tratamento farmacológico , Alcoolismo/etiologia , Alcoolismo/patologia , Animais , Animais não Endogâmicos , Sangue/efeitos dos fármacos , Células Sanguíneas/efeitos dos fármacos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Furaldeído/toxicidade , Masculino , Metanol/toxicidade , Ratos
20.
Folia Med (Plovdiv) ; 41(1): 43-5, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10462919

RESUMO

The cytotoxicity of test agents on serum-free McCoy cultures has not been studied at all. The cytotoxic effect of EDTA, methanol, DMSO, and cycloheximide on serum-free McCoy-Plovdiv cell culture (SF) was detected visually on inverted microscope and quantitatively by tests for viability (NR) and total protein (KBP). The IC50 values for the tested chemicals were calculated. SF showed the lowest IC50 values for cycloheximide, DMSO and EDTA and the highest for methanol according to both tests. EDTA, methanol, DMSO and cycloheximide had dose-effect relationship in the cell test systems after treatment. The data indicate that McCoy-Plovdiv cell line is a suitable serum-free cell system for in vitro cytotoxic studies.


Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Técnicas de Cultura de Células/métodos , Linhagem Celular , Quelantes/toxicidade , Meios de Cultura Livres de Soro , Cicloeximida/toxicidade , Dimetil Sulfóxido/toxicidade , Ácido Edético/toxicidade , Humanos , Metanol/toxicidade , Solventes/toxicidade
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