RESUMO
Abstract Context: Ulva lactuca Linnaeus (Chlorophyceae), a commonly distributed seaweed, is rich in polysaccharide but has not been studied extensively. Objective: The present study investigated the effects of crude fraction of Ulva lactuca polysaccharide (ULP) on d-galactosamine (d-Gal)-induced DNA damage, hepatic oxidative stress, and necrosis in rats. Materials and methods: The rats were treated with ULP (100 mg/kg, orally) for 4 weeks before a single intraperitoneal injection of d-Gal (500 mg/kg). In addition to liver cell necrosis and DNA damage, antioxidant parameters, such as lipid peroxide (LPO), superoxide dismutase, and catalase, and histopathology of liver tissue were evaluated. Results: ULP pre-treatment significantly attenuated a d-Gal-induced decrease in DNA and RNA levels (3.67 ± 0.38) and (5.42 ± 0.46), respectively. Comet tail length and acridine staining confirmed the number of cells undergoing necrosis were relatively lower in ULP treated rats (30 µm and 8-10% of counted cells) compared to rats treated with d-Gal (60 µm and 16% of counted cells). Biochemical (LPO, SOD and CAT) and histological evaluation (p < 0.01) confirmed the anti-hepatotoxic and antioxidant property of crude polysaccharide against d-Gal-induced elevation of LPO and infiltration of inflammatory cells into liver tissue. Discussion and conclusion: Although our previous studies have reported on the protective role of ULP against liver toxicity, our present findings show that ULP improved the hepatic antioxidant defense system against d-Gal-induced DNA damage and necrosis in rats.
RESUMO
To find whether pretreatment of Ulva lactuca polysaccharide (ULP) extract could be effective against D-Galactosamine (500 mg/kg body weight, i.p.) induced anomaly in rat. Serum total cholesterol (TC), triglycerides (TG), free fatty acid (FFA), phospholipids (PL), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), tissue lipoperoxides (LPO), hepatic protein thiols, non-enzymatic anti-oxidants glutathione (GSH) and vitamins (E and C) were examined using spectrophotometer. The ultra structural changes of liver during D-Galactosamine and protection offered by ULP were examined by electron microscopy. Seaweed histology and chemical composition of polysaccharides in seaweed were examined. Alcian blue staining showed the presence of sulphated polysaccharide with total sugar (65.4%), sulphate (17.4%), and uronic acid (17.2%) content. D-Galactosamine intoxicated rats showed significant (p<0.01) liver damage with acute aberration in serum lipid profile, hepatic protein thiols and tissue non-enzymatic anti-oxidants. Assorted deposits of lipid droplets and abnormal appearance of mitochondria was observed in electron microscopy study. Rats pretreated with ULP (30 mg/kg body weight/day/for 21 days) showed a significant inhibition (p<0.05) against abnormality induced by d-Galactosamine. U.lactuca exhibit anti-peroxidative and anti-hyperlipidemic property.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Galactosamina/toxicidade , Hiperlipidemias/tratamento farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Polissacarídeos/farmacologia , Ulva/química , Animais , Doença Hepática Induzida por Substâncias e Drogas/patologia , Esquema de Medicação , Hiperlipidemias/induzido quimicamente , Fígado/patologia , Masculino , Polissacarídeos/administração & dosagem , Polissacarídeos/química , Ratos , Ratos WistarRESUMO
The present study was aimed to examine the protective effects of Sargassum polycystum (Phaeophyceae) alcoholic extract on changes in liver mitochondrial enzymes against acetaminophen induced toxic hepatitis in experimental rats. The levels of protein, lipid peroxide, glutathione (GSH) in mitochondrial fraction, superoxide dismutase (SOD) and catalase (CAT) were also determined. The activities of tricarboxylic acid enzymes such as isocitrate dehydrogenase (ICD), alpha-ketoglutarate dehydrogenase (alpha-KGD), succinate dehydrogenase (SD), malate dehydrogenase (MD), NADH dehydrogenase, and cytochrome-c-oxidase were determined in mitochondrial fraction. The rats intoxicated with acetaminophen showed significant elevation in the levels of lipid peroxides with decreased levels of protein, GSH, SOD, CAT and impaired tricarboxylic acid cycle enzyme activities. The prior oral administration of S. polycystum alcoholic extract showed significant diminution in the severity of toxic hepatitis in acetaminophen-induced rats by maintaining the activities of tricarboxylic acid enzymes with concomitant improvement in the hepatic mitochondrial antiperoxidative status when compared with intoxicated animals. The results obtained in the present study indicate that the protective effects of S. polycystum extract may be due to the presence of some active compounds that are inhibitory against the free radicals generated during lipid peroxidation in acetaminophen induced toxic hepatitis.
Assuntos
Acetaminofen/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Extratos Vegetais/farmacologia , Sargassum/química , Animais , Radicais Livres , Masculino , Mitocôndrias Hepáticas/enzimologia , Ratos , Ratos WistarRESUMO
Effect of pre-treatment with hot water extract of marine brown alga Sargassum polycystum C.Ag. (100 mg/kg body wt, orally for period of 15 days) on HCl-ethanol (150 mM of HCl-ethanol mixture containing 0.15 N HCl in 70% v/v ethanol given orally) induced gastric mucosal injury in rats was examined with respect to lipid peroxides, antioxidant enzyme status, acid/pepsin and glycoproteins in the gastric mucosa. The levels of lipid peroxides of gastric mucosa and volume, acidity of the gastric juice were increased with decreased levels of antioxidant enzymes and glycoproteins were observed in HCl-ethanol induced rats. The rats pre-treated with seaweed extract prior to HCl-ethanol induction reversed the depleted levels of antioxidant enzymes and reduced the elevated levels of lipid peroxides when compared with HCl-ethanol induced rats. The levels of glycoproteins and alterations in the gastric juice were also maintained at near normal levels in rats pre-treated with seaweed extract. The rats given seaweed extract alone did not show any toxicity, which was confirmed by histopathological studies. These results suggest that the seaweed extract contains some anti-ulcer agents, which may maintain the volume/acidity of gastric juice and improve the gastric mucosa antioxidant defense system against HCl-ethanol induced gastric mucosal injury in rats.
Assuntos
Mucosa Gástrica/efeitos dos fármacos , Ácido Clorídrico/toxicidade , Sargassum , Úlcera Gástrica/prevenção & controle , Água , Animais , Etanol/toxicidade , Mucosa Gástrica/patologia , Temperatura Alta , Masculino , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Sargassum/isolamento & purificação , Úlcera Gástrica/patologiaRESUMO
In this study we used liver mitochondrial and microsomal fraction from rats pretreated with seaweed Ulva lactuca polysaccharide extract (ULP - 200mg/kg body weight, daily for 21 days, oral gavage) on D-Galactosamine (500mg/kg body weight, intraperitoneally) challenge. Effectiveness of ULP was determined based on functional status of trichloro acetic acid (TCA), urea cycle, and microsomal enzymes. The composition of sulfate polysaccharide content such as total sugars, sulfate and uronic acid were examined. In addition the fine ultra structural changes were examined using electron microscopy (EM). We observed significant (p<0.001) mitochondrial and microsomal abnormalities during liver damage by D-Galactosamine, consequently altering enzymes of energy metabolism. Electron microscopy of D-Galactosamine intoxicated rat liver tissue revealed the swelling and loss of mitochondrial cristae. Conversely the rats pretreated with ULP against D-Galactosamine challenge prevented (p<0.05) the significant abnormality of TCA, microsomal enzymes and severity of mitochondria as observed in EM study in rats injected with D-Galactosamine alone. However no effective prevention was observed in urea cycle enzymes among D-Galactosamine and treatment group rats. These results showed the effectiveness of ULP in stabilizing the functional status of mitochondrial and microsomal membrane which might be due to the presence of sulfated polysaccharide that could prevented the oxidative stress induced by D-Galactosamine intoxication.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Microssomos Hepáticos/efeitos dos fármacos , Mitocôndrias Hepáticas/efeitos dos fármacos , Polissacarídeos/farmacologia , Ulva/química , Administração Oral , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Galactosamina/administração & dosagem , Galactosamina/toxicidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/enzimologia , Hepatócitos/ultraestrutura , Injeções Intraperitoneais , Masculino , Microssomos Hepáticos/enzimologia , Microssomos Hepáticos/ultraestrutura , Mitocôndrias Hepáticas/enzimologia , Mitocôndrias Hepáticas/ultraestrutura , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/enzimologia , Membranas Mitocondriais/ultraestrutura , Extratos Vegetais/farmacologia , Polissacarídeos/administração & dosagem , Polissacarídeos/química , Ratos , Ratos Wistar , Ácido Tricloroacético/metabolismo , Ureia/metabolismoRESUMO
Studies on the lipid peroxidation and antioxidant changes and their significance during myocardial injury have provided a new insight into the pathogenesis of heart disease. The heart failure subsequent to myocardial infarction may be associated with an antioxidant deficit as well as increased myocardial oxidative stress. The present study was designed to evaluate the effect of the combination of ferulic acid and ascorbic acid on antioxidant defense system and lipid peroxidation against isoproterenol (ISO)-induced myocardial infarction in rats. Induction of rats with isoproterenol (150 mg/kg body weight daily, i.p.) for 2 days resulted in a marked elevation in lipid peroxidation, serum marker enzymes (LDH, CPK, GOT, and GPT), and a significant decrease in activities of endogenous antioxidants (SOD, GPx, GST, CAT, and GSH). Pre-co-treatment with the combination of ferulic acid (20 mg/kg body weight/day) and ascorbic acid (80 mg/kg body weight/day) orally for 6 days, significantly attenuated these changes when compared to the individual treatment groups. Histopathological observations were also in correlation with the biochemical parameters. Thus, ferulic acid and ascorbic acid significantly counteracted the pronounced oxidative stress effect of ISO by the inhibition of lipid peroxidation, restoration of antioxidant status, and myocardial marker enzymes levels. In conclusion, these findings indicate the synergistic protective effect of ferulic acid and ascorbic acid on lipid peroxidation and antioxidant defense system during ISO-induced myocardial infarction and associated oxidative stress in rats.
Assuntos
Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Ácidos Cumáricos/uso terapêutico , Sequestradores de Radicais Livres/uso terapêutico , Isoproterenol/toxicidade , Infarto do Miocárdio/prevenção & controle , Animais , Interações Medicamentosas , Sinergismo Farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Ratos , Ratos WistarRESUMO
Lipid peroxidation is believed to play an important role in the pathogenesis of several diseases, such as cancer, diabetic mellitus and liver injury. Aqueous and ethanol extracts of Sargassum polycystum C. Agardh (Phaeophyta) were screened for their protective effects against acetaminophen (ACP; Paracetamol)-induced lipid peroxidation in rats. A single dose of acetaminophen significantly elevated the levels of lipid peroxides (LPO) with decreased levels of free radical scavenger enzymes (SOD, CAT, GSH, GPx, GST) in liver homogenate. The oral pretreatment of rats with ethanol and aqueous extracts of Sargassum polycystum C. Agardh (100 mg, 200 mg[sol ]kg body wt[sol ]day respectively, for a period of 15 days) significantly reduced the acetaminophen-induced oxidative stress in rats. The animals treated with the ethanol and aqueous extracts alone did not show any toxicity on liver tissue. This observation shows that the seaweed crude extracts probably acted to protect against acetaminophen-induced lipid peroxidation through their free radical scavenging property.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Peroxidação de Lipídeos/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Sargassum , Acetaminofen , Animais , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/uso terapêutico , Ratos , Ratos WistarRESUMO
The effect of Sargassum polycystum crude extract on lipid metabolism was examined against acetaminophen-induced (800 mg/kg body wt., intraperitoneally) hyperlipidemia during toxic hepatitis in experimental rats. The animals intoxicated with acetaminophen showed significant elevation in the levels of cholesterol, triglycerides and free fatty acid in both serum and liver tissue. The levels of tissue total lipids and serum LDL-cholesterol were also elevated with depleted levels of serum HDL-cholesterol and tissue phospholipid. The acetaminophen-induced animals showed significant alterations in the activities of lipid metabolizing enzymes serum lecithin cholesterol acyl transferase (LCAT) and hepatic triglyceride lipase (HTGL). The levels of liver tissue fatty acids (saturated, mono and polyunsaturated) such as palmitic acid, stearic acid, oleic acid, linoleic acid, arachidonic acid and linolenic acid monitored by gas chromatography were considerably altered in acetaminophen intoxicated animals when compared with control animals. The prior oral administration of Sargassum polycystum (200 mg/kg body wt./day for a period of 15 days) crude extract showed considerable prevention in the severe disturbances of lipid profile and metabolizing enzymes triggered by acetaminophen during hepatic injury. Liver histology also showed convincing supportive evidence regarding their protective nature against fatty changes induced during acetaminophen intoxication. Thus the present study indicates that the protective nature of Sargassum polycystum extract may be due to the presence of active compounds possessing antilipemic property against acetaminophen challenge.