RESUMEN
BACKGROUND: Chronic administration of D-galactose (GAL) induces changes that resemble natural aging in rodents. Oxidative stress and Advanced Glycation End products (AGE) formation play a role in GAL-induced aging. Carnosine (CAR; ß-alanyl-L-histidine) has antioxidant and anti-glycating actions and may be a potential therapeutic agent in aging due to these properties. The effect of CAR supplementation on AGE levels and oxidative stress parameters was investigated in serum, liver and brain tissues in GAL-treated rats. METHODS: GAL (300 mg/kg; s.c.; 5 days per week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days per week) was applied to male rats for two months. AGE, Advanced Oxidized Protein Products (AOPP), Protein Carbonyl (PC) and Malondialdehyde (MDA) levels together with Reactive Oxygen Species (ROS) formation and Ferric Reducing Antioxidant Power (FRAP) values were determined. RESULTS: GAL treatment elevated AGE levels, ROS formation and protein and lipid oxidation products in serum and examined tissues. CAR treatment was observed to decrease significantly glycooxidative stress in serum, liver and brain tissues of GAL-treated rats. CONCLUSION: Our results indicate that CAR may be useful for decreasing oxidative stress and glycation products in GAL-induced aging model in rats.
Asunto(s)
Antioxidantes/farmacología , Encéfalo/efectos de los fármacos , Carnosina/farmacología , Galactosa/toxicidad , Productos Finales de Glicación Avanzada/sangre , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Productos Avanzados de Oxidación de Proteínas/sangre , Factores de Edad , Envejecimiento/sangre , Animales , Biomarcadores/sangre , Encéfalo/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Masculino , Malondialdehído/sangre , Carbonilación Proteica/efectos de los fármacos , Ratas Wistar , Especies Reactivas de Oxígeno/sangreRESUMEN
AIM: Increases in oxidative stress and advanced glycation end-products (AGE) formation play an important role in the pathogenesis of aging. Carnosine (CAR; ß-alanyl-L-histidine) has anti-oxidant and antiglycating properties. We investigated the effect of CAR supplementation on AGE levels, and protein and lipid oxidation products in the serum and liver tissue in aged rats. METHODS: Young (3 months-of-age) and aged (20 months-of-age) rats were injected with CAR (250 mg/kg/daily; i.p.; 5 days per week) for 2 months. At the end of this period, AGE, protein carbonyl, advanced oxidized protein products, and malondialdehyde levels were determined in the serum and liver tissue. Furthermore, reactive oxygen species formation and ferric reducing anti-oxidant power values were measured. RESULTS: AGE, malondialdehyde, protein carbonyl and advanced oxidized protein products levels, and reactive oxygen species formation were higher in the serum and liver tissue of aged rats compared with young rats. CAR treatment was observed to significantly decrease AGE, malondialdehyde, protein carbonyl and advanced oxidized protein products levels, and reactive oxygen species formation in the serum and liver of aged rats. CONCLUSIONS: These results clearly show that CAR might be useful for decreasing glycoxidant stress in aged rats. Geriatr Gerontol Int 2017; 17: 2610-2614.
Asunto(s)
Envejecimiento/efectos de los fármacos , Carnosina/uso terapéutico , Productos Finales de Glicación Avanzada/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes , Femenino , Hígado/efectos de los fármacos , Masculino , Oxidantes , Ratas , Ratas WistarRESUMEN
Steatosis, the first lesion in non-alcoholic fatty liver disease (NAFLD), may progress to fibrosis, cirrhosis, and hepatocellular carcinoma. Steatosis predisposes the liver to oxidative stress, inflammation, and cytokines. Betaine (BET) has antioxidant, antiinflammatory and hepatoprotective effects. However, the effects of BET on liver fibrosis development are unknown. Rats were treated with high-fat diet (60% of total calories from fat) for 14weeks. Carbon tetrachloride (0.2mL/kg; two times per week; i.p.) was administered to rats in the last 6weeks with/without commercial food containing BET (2%; w/w). Serum liver function tests and tumor necrosis factor-α, insulin resistance, hepatic triglyceride (TG) and hydroxyproline (HYP) levels and oxidative stress parameters were determined along with histopathologic observations. Alpha-smooth muscle-actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) and type I collagen (COL1A1) protein expressions and mRNA expressions of matrix metalloproteinase-2 (MMP-2) and its inhibitors (TIMP-1 and TIMP-2) were evaluated. BET decreased TG and HYP levels, prooxidant status and fibrotic changes in the liver. α-SMA, COL1A1 and TGF-ß1 protein expressions, MMP-2, TIMP-1, and TIMP-2 mRNA expressions diminished due to BET treatment. BET has an antifibrotic effect and this effect may be related to its antioxidant and antiinflammatory actions together with suppression on HSC activation.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Betaína/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Hígado/efectos de los fármacos , Actinas/metabolismo , Animales , Tetracloruro de Carbono/toxicidad , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Dieta Alta en Grasa , Femenino , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/inducido químicamente , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The aim of this study was to investigate the effect of betaine (BET) on alcoholic liver fibrosis in rats. Fibrosis was experimentally generated with ethanol plus carbon tetrachloride (ETH+CCl4) treatment. Rats were treated with ETH (5% v/v in drinking water) for 14 weeks. CCl4 was administered intraperitoneally (i.p.) 0.2mL/kg twice a week to rats in the last 6 weeks with/without commercial food containing BET (2% w/w). Serum hepatic damage markers, tumor necrosis factor-α, hepatic triglyceride (TG) and hydroxyproline (HYP) levels, and oxidative stress parameters were measured together with histopathologic observations. In addition, α-smooth muscle-actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) and type I collagen (COL1A1) protein expressions were assayed immunohistochemically to evaluate stellate cell (HSC) activation. mRNA expressions of matrix metalloproteinase-2 (MMP-2) and its inhibitors (TIMP-1 and TIMP-2) were also determined. BET treatment diminished TG and HYP levels; prooxidant status and fibrotic changes; α-SMA, COL1A1 and TGF-ß protein expressions; MMP-2, TIMP-1 and TIMP-2 mRNA expressions in the liver of fibrotic rats. In conclusion, these results indicate that the antifibrotic effect of BET may be related to its suppressive effects on oxidant and inflammatory processes together with HSC activation in alcoholic liver fibrosis.
Asunto(s)
Betaína/uso terapéutico , Células Estrelladas Hepáticas/efectos de los fármacos , Cirrosis Hepática Alcohólica/prevención & control , Cirrosis Hepática Experimental/prevención & control , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Betaína/administración & dosificación , Biomarcadores/sangre , Peso Corporal/efectos de los fármacos , Femenino , Células Estrelladas Hepáticas/inmunología , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Peroxidación de Lípido/efectos de los fármacos , Hígado/inmunología , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática Alcohólica/inmunología , Cirrosis Hepática Alcohólica/metabolismo , Cirrosis Hepática Alcohólica/patología , Cirrosis Hepática Experimental/inmunología , Cirrosis Hepática Experimental/metabolismo , Cirrosis Hepática Experimental/patología , Pruebas de Función Hepática , Tamaño de los Órganos/efectos de los fármacos , Ratas Sprague-DawleyRESUMEN
BACKGROUND: This study aimed at investigating the possible protective effect of erythropoietin beta on experimental diabetic nephropathy (DN) model in rats. METHODS: Sprague Dawley rats (n = 32) were allocated into 4 equal groups of 8 each, the control (Group C), diabetes (Group D), erythropoietin beta (Group E), and erythropoietin beta treated DN (Group E + D) groups. Streptozocin (65 mg/kg) was used to induce diabetes in 10-week old rats. Erythropoietin beta was given intraperitoneally at a dose of 500 IU/kg/3 days of a week for 12 weeks. Renal function parameters, intrarenal levels and activities of oxidative stress biomarkers, serum inflammatory parameters and kidney histology were determined. RESULTS: Group E + D had lower mean albumin-to-creatinine ratio (p < 0.001) as well as higher creatinine clearance (p = 0.035) than the diabetic rats (Group D). Intrarenal malondialdehyde levels were significantly lower (p = 0.004); glutathione (GSH) levels (p = 0.003), GSH peroxidase (p = 0.004) and superoxide dismutase (p < 0.005) activities of renal tissue were significantly higher in Group E + D than in Group D. The mean serum levels of interleukin-4 (p < 0.005), interleukin 1 beta (p = 0.012), interferon gamma (p = 0.018) and tumor necrosis factor alpha (p < 0.005) were significantly lower; serum levels of monocyte chemoattractant protein 1 (p = 0.018) was significantly higher in Group E + D when compared to Group D. The mean scores of tubulointerstitial inflammation (p = 0.004), tubular injury (p = 0.013) and interstitial fibrosis (p = 0.003) were also lower in Group E + D when compared to Group D. CONCLUSION: Our data seem to suggest a potential role of erythropoietin beta for reducing the progression of DN in an experimental rat model. This protective effect is, in part, attributable to the suppression of the inflammatory response and oxidative damage.
Asunto(s)
Nefropatías Diabéticas/prevención & control , Modelos Animales de Enfermedad , Eritropoyetina/uso terapéutico , Animales , Citocinas/sangre , Nefropatías Diabéticas/enzimología , Nefropatías Diabéticas/metabolismo , Glutatión/metabolismo , Mediadores de Inflamación/sangre , Masculino , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismoRESUMEN
The aim of this study was to investigate the effect of carnosine (CAR) alone and together with vitamin E (Vit E) on alcoholic steatohepatitis (ASH) in rats. ASH was induced by ethanol (3 times; 5 g/kg; 12 h intervals, via gavage), followed by a single dose of lipopolysaccharide (LPS; 10 mg/kg; i.p.). CAR (250 mg/kg; i.p.) and Vit E (200 mg D-α-tocopherol/kg; via gavage) were administered 30 min before and 90 min after the LPS injection. CAR treatment lowered high serum transaminase activities together with hepatic histopathologic improvements in rats with ASH. Reactive oxygen species formation, malondialdehyde levels, myeloperoxidase activities and transforming growth factor ß1 (TGF-ß1) and collagen 1α1 (COL1A1) expressions were observed to decrease. These improvements were more remarkable in CAR plus Vit E-treated rats. Our results indicate that CAR may be effective in suppressing proinflammatory, prooxidant, and profibrotic factors in the liver of rats with ASH.
Asunto(s)
Antioxidantes/farmacología , Carnosina/farmacología , Etanol/toxicidad , Lipopolisacáridos/toxicidad , Estrés Oxidativo/efectos de los fármacos , alfa-Tocoferol/farmacología , Animales , Hígado , Masculino , Malondialdehído/metabolismo , RatasRESUMEN
D-galactose (GAL) has been used as an animal model for brain aging and antiaging studies. GAL stimulates oxidative stress in several tissues including brain. Carnosine (CAR; ß-alanil-L-histidine) and taurine (TAU; 2-aminoethanesulfonic acid) exhibit antioxidant properties. CAR and TAU have anti-aging and neuroprotective effects. We investigated the effect of CAR and TAU supplementations on oxidative stress and brain damage in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days per week) or TAU (2.5% w/w; in rat chow) for 2 months. Brain malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione transferase (GST) and acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brains by immunohistochemistry. GAL treatment increased brain MDA and PC levels and AChE activities. It decreased significantly brain GSH levels, SOD and GSH-Px but not GST activities. GAL treatment caused histopathological changes and increased apoptosis. CAR and TAU significantly reduced brain AChE activities, MDA and PC levels and elevated GSH levels in GAL-treated rats. CAR, but not TAU, significantly increased low activities of SOD and GSH-Px. Both CAR and TAU diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. Our results indicate that CAR and TAU may be effective to prevent the development of oxidative stress, apoptosis and histopathological deterioration in the brain of GAL-treated rats.
Asunto(s)
Antioxidantes/farmacología , Carnosina/farmacología , Galactosa/metabolismo , Estrés Oxidativo/efectos de los fármacos , Taurina/farmacología , Envejecimiento , Animales , Apoptosis/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Histidina/metabolismo , Masculino , Malondialdehído/metabolismo , Ratas Wistar , Superóxido Dismutasa/metabolismo , Taurina/metabolismoRESUMEN
D-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of whole fresh blueberry (BB) (Vaccinium corymbosum L.) treatment on oxidative stress in age-related brain damage model. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with 5 % (BB1) and 10 % (BB2) BB containing chow for two months. Malondialdehyde (MDA),protein carbonyl (PC) and glutathione (GSH) levels, and Cu Zn-superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities as well as acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brain by immunohistochemistry. MDA and PC levels and AChE activity increased, but GSH levels, SOD and GSH-Px activities decreased together with histopathological structural damage in the brain of GAL-treated rats. BB treatments, especially BB2 reduced MDA and PC levels and AChE activity and elevated GSH levels and GSH-Px activity. BB1 and BB2 treatments diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. These results indicate that BB partially prevented the shift towards an imbalanced prooxidative status and apoptosis together with histopathological amelioration by acting as an antioxidant (radical scavenger) itself in GAL-treated rats.
Asunto(s)
Arándanos Azules (Planta) , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/prevención & control , Galactosa/toxicidad , Estrés Oxidativo/fisiología , Extractos Vegetales/uso terapéutico , Animales , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Lesiones Encefálicas/patología , Galactosa/antagonistas & inhibidores , Masculino , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: The aim of the present study was to investigate the effect of combination of aliskiren with paricalcitol on experimental diabetic nephropathy (DN) model in rats. METHODS: Forty male Sprague Dawley rats were divided into 5 groups of 8 rats each, namely the control (Group C), diabetes (Group D), aliskiren (Group A), paricalcitol (Group P), and aliskiren plus paricalcitol (Group A+P) groups. Aliskiren was given by oral-gavage at a dose of 50 mg/kg/day once daily for 12 weeks. Paricalcitol was given by intraperitoneally at a dose of 0,4 µg/kg/three day of week for 12 weeks. Renal function parameters, oxidative stress biomarkers, mRNA expression of renin-angiotensin system parameters and kidney histology were determined. RESULTS: Group A+P had lower mean albümin-to-creatinine ratio (ACR) (p=0.004) as well as higher creatinine clearance (CCr) (p<0.005) than the diabetic rats (Group D). Combination therapy significantly increased CCr (Group A+P vs. Group A, p<0.005; Group A+P vs. Group P, p=0.022) and reduced ACR (Group A+P vs. Group A, p=0.018; Group A+P vs. Group P, p<0.005) when compared to monotherapy. Serum malondialdehyde levels were significantly lower (p=0.004); glutathion levels (p=0.003), glutathion peroxidase (p=0.004) and superoxide dismutase (p<0.005) activities were significantly higher in group A+P than in group D. The mean scores of mRNA expression of renin (p<0.005), angiotensin II (p=0.012) and angiotensin type 1 receptor (p=0.018) in group A+P were significantly lower. Although combination therapy showed no additional effect on oxidative system, renin-angiotensin system and renal histology, aliskiren plus paricalcitol significantly decreased interstitial fibrosis volume when compared to monotherapy (Group A+P vs. Group A, p<0.005; Group A+P vs. Group P, p=0.002). CONCLUSION: Our data seem to suggest a potential role of aliskiren plus paricalcitol acting synergystically for reducing the progression of diabetic nephropathy in an experimental rat model.
Asunto(s)
Amidas/uso terapéutico , Antihipertensivos/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Nefropatías Diabéticas/tratamiento farmacológico , Ergocalciferoles/uso terapéutico , Fumaratos/uso terapéutico , Animales , Antioxidantes/metabolismo , Biomarcadores/sangre , Nefropatías Diabéticas/patología , Progresión de la Enfermedad , Quimioterapia Combinada , Riñón/patología , Pruebas de Función Renal , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Sistema Renina-Angiotensina/efectos de los fármacosRESUMEN
AIM: Olive leaf (Olea europaea L.) extract (OLE) is a powerful anti-oxidant rich in polyphenols. As oxidative stress plays an important role in aging, we investigated the effect of OLE on oxidative stress in the liver, heart and brain of aged rats. METHODS: Young (age 3 months) and aged (age 20 months) Wistar rats were used. Aged rats received OLE (500 and 1000 mg/kg/day) in drinking water for 2 months. Malondialdehyde (MDA), diene conjugate (DC), protein carbonyl (PC), glutathione (GSH), vitamin E and vitamin C levels, and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined. RESULTS: MDA, DC and PC levels increased in tissues of aged rats. GSH levels decreased in the liver, but not in the heart and brain. There was no change of other anti-oxidant parameters in tissues. Hepatic SOD and GSH-Px protein expressions also remained unchanged. OLE treatment caused decreased tissue MDA, DC and PC levels, and increased hepatic GSH levels in aged rats. Other anti-oxidant parameters, hepatic SOD and GSH-Px protein expressions did not alter in aged rats by OLE treatment. CONCLUSION: The present results suggest that OLE seems to be useful for decreasing oxidative stress in examined tissues by acting as an anti-oxidant itself without affecting the anti-oxidant system.
Asunto(s)
Antioxidantes/metabolismo , Hígado/metabolismo , Miocardio/metabolismo , Olea , Estrés Oxidativo/efectos de los fármacos , Fitoterapia/métodos , Extractos Vegetales/farmacología , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Animales , Modelos Animales de Enfermedad , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , EspectrofotometríaRESUMEN
D-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of carnosine (CAR) or taurine (TAU), having antioxidant effects, on hepatic injury and oxidative stress in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days/week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days/week) or TAU (2.5 % w/w; in rat chow) for 2 months. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and hepatic malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-0050x), and glutathione transferase (GST) activities were determined. Hepatic expressions of B cell lymphoma-2 (Bcl-2), Bax and Ki-67 were evaluated. Serum ALT, AST, hepatic MDA, and PC levels were observed to increase in GAL-treated rats. Hepatic Bax expression, but not Bcl-2, increased, Ki-67 expression decreased. GAL treatment caused decreases in GSH levels, SOD and GSH-Px activities in the liver. Hepatic mRNA expressions of SOD, but not GSH-Px, also diminished. CAR or TAU treatments caused significant decreases in serum ALT and AST activities. These treatments decreased apoptosis and increased proliferation and ameliorated histopathological findings in the livers of GAL-treated rats. Both CAR and TAU reduced MDA and PC levels and elevated GSH levels, SOD and GSH-Px (non significant in TAU + GAL group) activities. These treatments did not alter hepatic mRNA expressions of SOD and GSH-Px enzymes. Our results indicate that CAR and TAU restored liver prooxidant status together with histopathological amelioration in GAL-induced liver damage
Asunto(s)
Animales , Ratas , Carnosina/farmacocinética , Taurina/farmacocinética , Estrés Oxidativo , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/tratamiento farmacológico , Galactosa/efectos adversos , Modelos Animales de Enfermedad , Sustancias Protectoras/farmacocinéticaRESUMEN
AIM: d-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of whole fresh blueberry (BB; Vaccinium corymbosum L.) treatment on oxidative stress in age-related liver injury model. METHODS: Rats received GAL (300 mg/kg, s.c.; 5 days per week) alone or together with 5% (BB1) and 10% (BB2) BB-containing chow for 2 months. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and hepatic malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels, and CuZn-superoxide dismutase (SOD1), glutathione peroxidase (GPx1) and glutathione transferase (GST) activities together with mRNA expressions of SOD1, GPx1, MnSOD (SOD2) and phospholipid hydroperoxide glutathione peroxidase (GPx4) were determined in GAL-treated rats. RESULTS: MDA and PC levels increased, but GSH levels, SOD1 and GPx1 activities decreased together with histopathological structural damage in the liver in GAL-treated rats. There was no change in hepatic mRNA expressions of SOD2 and GPx1, but SOD1 and GPx4 expressions decreased. BB1 and BB2 caused significant decreases in serum ALT and AST activities together with the amelioration in histopathological findings in GAL-treated rats. Both BB1 and BB2 reduced MDA and PC levels, and elevated GSH levels, and SOD1 and GPx1 activities. However, hepatic mRNA expressions of SOD1, SOD2, GPx1 and GPx4 remained unchanged in GAL-treated rats. CONCLUSIONS: These results show that BB restored liver pro-oxidant status together with histopathological amelioration by acting as an anti-oxidant (radical scavenger) itself without affecting mRNA expressions of anti-oxidant enzymes in GAL-treated rats.
Asunto(s)
Arándanos Azules (Planta) , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Galactosa/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Animales , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Ratas , Ratas WistarRESUMEN
D-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of carnosine (CAR) or taurine (TAU), having antioxidant effects, on hepatic injury and oxidative stress in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days/week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days/week) or TAU (2.5 % w/w; in rat chow) for 2 months. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and hepatic malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-0050x), and glutathione transferase (GST) activities were determined. Hepatic expressions of B cell lymphoma-2 (Bcl-2), Bax and Ki-67 were evaluated. Serum ALT, AST, hepatic MDA, and PC levels were observed to increase in GAL-treated rats. Hepatic Bax expression, but not Bcl-2, increased, Ki-67 expression decreased. GAL treatment caused decreases in GSH levels, SOD and GSH-Px activities in the liver. Hepatic mRNA expressions of SOD, but not GSH-Px, also diminished. CAR or TAU treatments caused significant decreases in serum ALT and AST activities. These treatments decreased apoptosis and increased proliferation and ameliorated histopathological findings in the livers of GAL-treated rats. Both CAR and TAU reduced MDA and PC levels and elevated GSH levels, SOD and GSH-Px (non significant in TAU + GAL group) activities. These treatments did not alter hepatic mRNA expressions of SOD and GSH-Px enzymes. Our results indicate that CAR and TAU restored liver prooxidant status together with histopathological amelioration in GAL-induced liver damage.
Asunto(s)
Antioxidantes/farmacología , Carnosina/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Galactosa/toxicidad , Hígado/metabolismo , Estrés Oxidativo/efectos de los fármacos , Taurina/farmacología , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Malondialdehído/metabolismo , Carbonilación Proteica , Ratas , Ratas WistarRESUMEN
Oxidative stress plays an important role in aging. Effects of several antioxidants on age-related oxidative stress have been investigated. Carnosine (CAR) and betaine have antioxidant actions. The combination of CAR with vitamin E(CAR+E) increases its antioxidant efficiency. We investigated the effects of CAR+E and betaine treatments on oxidative and antioxidative status in liver, heart and brain tissues of aged rats. Experiments were carried out on young (5 months)and aged (22 months) male Wistar rats. Aged rats were given CAR (250 mg/kg; i.p.; 5 days per week) and vitamin E (200mg/kg; i.m.; twice per week) or betaine (1% w/v) for two months. Malondialdehyde (MDA) and diene conjugate (DC)levels and antioxidants were measured. MDA and DC levels were higher in tissues of aged rats than young rats. Glutathione(GSH) levels decreased in liver, but not heart and brain. There were no changes in vitamin E and vitamin C levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities in tissues of aged rats. CAR+E treatment was observed to decrease MDA and DC levels in tissues of aged rats. However, betaine decreased only hepatic MDA and DC levels. Both CAR+E and betaine increased hepatic GSH and vitamin E levels, but these treatments did not affect antioxidant enzyme activities. These results suggest that CAR+E treatment seems to be useful to decrease oxidative stress in liver, heart and brain tissues, but betaine is only effective in liver tissue of aged rats.
Asunto(s)
Envejecimiento/metabolismo , Betaína/farmacología , Encéfalo/metabolismo , Carnosina/farmacología , Hígado/metabolismo , Miocardio/metabolismo , Estrés Oxidativo/efectos de los fármacos , Vitamina E/farmacología , Animales , Antioxidantes/farmacología , Peso Corporal/fisiología , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Modelos Animales , Estrés Oxidativo/fisiología , Ratas , Ratas WistarRESUMEN
We investigated the effect of blueberries (BB) on lipids and oxidative stress parameters in hypercholesterolemic guinea pigs. The animals were fed for 75 d on a high-cholesterol (HC) diet supplemented with fresh BB. BB reduced oxidative stress and cholesterol accumulation in the aorta and liver of the guinea pigs. This effect may be related to its antioxidative potential and lipid-reducing effect.
Asunto(s)
Aorta/metabolismo , Arándanos Azules (Planta) , Colesterol en la Dieta/administración & dosificación , Hipercolesterolemia/dietoterapia , Hígado/metabolismo , Estrés Oxidativo , Animales , Anticolesterolemiantes/farmacología , Aorta/efectos de los fármacos , Aorta/patología , Dieta Alta en Grasa , Flavonoles/farmacología , Cobayas , Hipercolesterolemia/etiología , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patología , Metabolismo de los Lípidos , Peroxidación de Lípido , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Polifenoles/farmacologíaRESUMEN
BACKGROUND: Endotoxins can cause serious organ damage and death by triggering the secretion of pro-inflammatory cytokines such as TNF-alpha, IL-6 and IL-1beta in bacterial infections. OBJECTIVES: The goal of this study was to evaluate the effects of a high dose (3000 U/kg) of erythropoietin-beta (EPO) on inflammatory cytokine levels, renal function and histological changes during the early period of Lipopolysaccharide (LPS)-induced endotoxemia using a rat model. MATERIAL AND METHODS: Male Sprague Dawley (350-400 g) rats were randomized into 3 groups: Control group (n = 7); LPS group (received 20 mcg/kg LPS through intraperitoneal (i.p.) injection (n = 7); LPS+EPO group (received 3000 U/kg, ip 30 minutes before LPS administration (n = 7). Four hours after the administration of LPS, kidney tissue and serum samples were collected. Kidney function parameters, TNF-alpha, IL-6, IL-1beta, C reactive protein (CRP) and complete blood counts (CBC) were measured. The severity of renal tubular injury and caspase-9 immunoreactive cells was expressed as a percentage. RESULTS: Serum levels of urea, creatinine, TNF-alpha, IL-6 and IL-1beta were significantly increased in the LPS group (p < 0.0001 - p = 0.04) and were lower in LPS+EPO group (p < 0.0001, p = 0.01, p = 0.02, p = 01 and p < 0.0001, respectively). Pretreatment with EPO significantly increased platelet counts (p = 0.00) and decreased white blood cell counts (p = 0.02). The renal tubular injury percentage was significantly higher in the LPS group than in the control and LPS+EPO groups (p = 0.002, p = 0.003, and p = 0.005, respectively) and caspase-9 expression was lower in the LPS+EPO and control groups than in the LPS group. CONCLUSIONS: EPO might have renoprotective effects against the inflammatory process and cell apoptosis during endotoxemia.