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AIM/INTRODUCTION: Diabetes Mellitus is a chronic degenerative disease, and its main biochemical characteristic is hyperglycemia due to impaired insulin secretion, resistance to peripheral actions of insulin, or both. Hyperglycemia causes dyslipidemia and stimulates oxidative damage, leading to the main symptoms, such as fatigue and culminates in diabetic complications. Previous studies have shown that ATP-sensitive potassium channels counteract muscle fatigue and metabolic stress in healthy mouse models. To determine the effect of diazoxide on muscle strength development during diabetes, we tested the effect of diazoxide in streptozotocin-diabetic rats in muscle function, lipid profile and oxidative stress biomarkers. MATERIALS AND METHODS: Wistar rats were divided into 4 groups of six animals each: (1) Control group, (2) diabetes group, (3) Control group + diazoxide, and (4) Diabetic + diazoxide (DB + DZX). 4 weeks after rats were sacrificed, soleus and extensor digitorum longus muscles (EDL) were extracted to prepare homogenates and serum was obtained for biochemical measurements. Oxidative damage was evaluated by the thiobarbituric acid method and the fluorescent for reactive oxygen species (ROS) probe 2,4-H2DCFDA, respectively. RESULTS: Diabetic rats with diazoxide administration showed an increase in the development of muscle strength in both muscles; in turn, the onset of fatigue was longer compared to the group of diabetic rats without treatment. Regarding the lipid profile, diazoxide decreased total cholesterol levels in the group of diabetic rats treated with diazoxide (xÌ 46.2 mg/dL) compared to the untreated diabetic group (xÌ =104.4 mg/dL); secondly, diazoxide decreased triglyceride concentrations (xÌ =105.3 mg/dL) compared to the untreated diabetic rats (xÌ =412.2 mg/dL) as well as the levels of very low-density lipoproteins (xÌ =20.4 mg/dL vs. xÌ =82.44 mg/dL). Regarding the various markers of oxidative stress, the diabetic group treated with diazoxide was able to reduce the concentrations of TBARS and total reactive oxygen species as well as preserve the concentrations of reduced glutathione. CONCLUSION: Diazoxide administration in diabetic rats increases muscle strength development in EDL and soleus muscle, decreases fatigue, reduces cholesterol and triglyceride concentrations and improves oxidative stress parameters such as TBARS, ROS, and glutathione status.
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Diabetes Mellitus Experimental , Hiperglicemia , Camundongos , Ratos , Animais , Diazóxido/efeitos adversos , Diazóxido/metabolismo , Estreptozocina/efeitos adversos , Estreptozocina/metabolismo , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Diabetes Mellitus Experimental/complicações , Substâncias Reativas com Ácido Tiobarbitúrico/efeitos adversos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Estresse Oxidativo , Hiperglicemia/complicações , Músculo Esquelético/metabolismo , Lipídeos , Triglicerídeos/efeitos adversos , Triglicerídeos/metabolismo , Colesterol/metabolismoRESUMO
Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia that affects practically all tissues and organs, being the brain one of most susceptible, due to overproduction of reactive oxygen species induced by diabetes. Eryngium carlinae is a plant used in traditional Mexican medicine to treat diabetes, which has already been experimentally shown have hypoglycemic, antioxidant and hypolipidemic properties. The green synthesis of nanoparticles is a technique that combines plant extracts with metallic nanoparticles, so that the nanoparticles reduce the absorption and distribution time of drugs or compounds, increasing their effectiveness. In this work, the antioxidant effects and mitochondrial function in the brain were evaluated, as well as the hypoglycemic and hypolipidemic effect in serum of both the aqueous extract of the aerial part of E. carlinae, as well as its combination with silver nanoparticles of green synthesis. Administration with both, extract and the combination significantly decreased the production of reactive oxygen species, lipid peroxidation, and restored the activity of superoxide dismutase 2, glutathione peroxidase, and electron transport chain complexes in brain, while that the extract-nanoparticle combination decreased blood glucose and triglyceride levels. The results obtained suggest that both treatments have oxidative activity and restore mitochondrial function in the brain of diabetic rats.
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Diabetes Mellitus Experimental , Eryngium , Nanopartículas Metálicas , Ratos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Estreptozocina/metabolismo , Estreptozocina/farmacologia , Estreptozocina/uso terapêutico , Eryngium/metabolismo , Prata/farmacologia , Prata/metabolismo , Prata/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Estresse Oxidativo , Ratos Wistar , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Peroxidação de Lipídeos , Encéfalo/metabolismo , Mitocôndrias/metabolismoRESUMO
Renal iron overload is a common complication of diabetes that leads to oxidative stress and mitochondrial dysfunction in the kidneys. This study investigated the effects of iron chelation using deferiprone on mitochondrial dysfunction and oxidative stress in the renal cortex of a murine model of type 2 diabetes. Diabetic rats were treated with deferiprone (50 mg/kg BW) for 16 weeks. Our results show that iron chelation with deferiprone significantly increased the nuclear accumulation of Nrf2, a transcription factor that regulates the expression of antioxidant enzymes. This led to enhanced antioxidant capacity, reduced production of reactive oxygen species, and improved mitochondrial bioenergetic function in diabetic rats. However, chronic iron chelation led to altered mitochondrial respiration and increased oxidative stress in non-diabetic rats. In conclusion, our findings suggest that iron chelation with deferiprone protects mitochondrial bioenergetics and mitigates oxidative stress in the renal cortex, involving the NRF2 pathway in type 2 diabetes.
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Secondary metabolites such as flavonoids are promising in the treatment of non-alcoholic fatty liver disease (NAFLD), which is one of the complications of diabetes due to oxidative stress and inflammation. Some plants, such as Eryngium carlinae, have been investigated regarding their medicinal properties in in vitro and in vivo assays, showing favorable results for the treatment of various diseases such as diabetes and obesity. The present study examined the antioxidant and anti-inflammatory effects of the phenolic compounds present in an ethyl acetate extract of the inflorescences of Eryngium carlinae on liver homogenates and mitochondria from streptozotocin (STZ)-induced diabetic rats. Phenolic compounds were identified and quantified by UHPLC-MS. In vitro assays were carried out to discover the antioxidant potential of the extract. Male Wistar rats were administered with a single intraperitoneal injection of STZ (45 mg/kg) and were given the ethyl acetate extract at a level of 30 mg/kg for 60 days. Phytochemical assays showed that the major constituents of the extract were flavonoids; in addition, the in vitro antioxidant activity was dose dependent with IC50 = 57.97 mg/mL and IC50 = 30.90 mg/mL in the DPPH and FRAP assays, respectively. Moreover, the oral administration of the ethyl acetate extract improved the effects of NAFLD, decreasing serum and liver triacylglycerides (TG) levels and oxidative stress markers and increasing the activity of the antioxidant enzymes. Likewise, it attenuated liver damage by decreasing the expression of NF-κB and iNOS, which lead to inflammation and liver damage. We hypothesize that solvent polarity and consequently chemical composition of the ethyl acetate extract of E. carlinae, exert the beneficial effects due to phenolic compounds. These results suggest that the phenolic compounds of the ethyl acetate extract of E. carlinae have antioxidant, anti-inflammatory, hypolipidemic, and hepatoprotective activity.
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Diabetes mellitus (DM) is a metabolic disorder characterized by persistent hyperglycemia. This state may lead to an increase in oxidative stress, which contributes to the development of diabetes complications, including diabetic kidney disease. Potentilla indica is a traditional medicinal herb in Asia, employed in the treatment of several diseases, including DM. In this study, we investigated the antioxidant effect of the ethyl acetate extract of Potentilla indica both in vitro and on kidneys of streptozotocin-induced diabetic male rats. Firstly, phytochemicals were identified via UPLC-MS/MS, and their in vitro antioxidant capabilities were evaluated. Subsequently, male Wistar rats were assigned into four groups: normoglycemic control, diabetic control, normoglycemic treated with the extract, and diabetic treated with the extract. At the end of the treatment, fasting blood glucose (FBG) levels, creatinine, blood urea nitrogen (BUN), and uric acid were estimated. Furthermore, the kidneys were removed and utilized for the determination of mitochondrial reactive oxygen species (ROS) production, mitochondrial respiratory chain complex activities, mitochondrial lipid peroxidation, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities. The in vitro findings showed that the major phytochemicals present in the extract were phenolic compounds, which exhibited a potent antioxidant activity. Moreover, the administration of the P. indica extract reduced creatinine and BUN levels, ROS production, and lipid peroxidation and improved mitochondrial respiratory chain complex activity and GSH-Px, SODk, and CAT activities when compared to the diabetic control group. In conclusion, our data suggest that the ethyl acetate extract of Potentilla indica possesses renoprotective effects by reducing oxidative stress on the kidneys of streptozotocin-induced diabetic male rats.
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Diabetes mellitus is a chronic degenerative disease characterized by hyperglycemia and oxidative stress. Iron catalyzes free radical overproduction. High iron concentrations have previously been reported to promote an increase in oxidative stress; however, the effect of iron restriction in diabetes has not yet been explored, so we tested to see if iron restriction in diabetic rats reduces oxidative damage and improved muscle function. Wistar rats were assigned to 4 groups: Control; Diabetic; Diabetic rats with a high iron diet, and Diabetic with dietary iron restriction. After 8 weeks the rats were sacrificed, the muscles were extracted to prepare homogenates, and serum was obtained for biochemical measurements. Low iron diabetic rats showed an increase in the development of muscle strength in both muscles. Dietary iron restriction decreased triglyceride concentrations compared to the untreated diabetic rats and the levels of extremely low-density lipoproteins. Aggravation of lipid peroxidation was observed in the diabetic group with a high iron diet, while these levels remained low with iron restriction. Iron restriction improved muscle strength development and reduced fatigue times; this was related to better lipid profile control and decreased oxidant stress markers.
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Obesity is a chronic disease that impairs skeletal muscle function, affects the ability to contract, and promotes the development of fatigue. For this reason, the study of treatments that seek to reduce the harmful effects of obesity on muscle tissue has been deepened. Diazoxide treatment and various exercise protocols have been proposed to protect skeletal muscle against oxidative stress and its effects. However, the intensity and duration of exercise combined with diazoxide that would obtain the best results for improving skeletal muscle function in obese rats is unknown. To this end, this study evaluated the effects of three different exercise intensities combined with diazoxide on contraction capacity, resistance to fatigue, markers of oxidative stress, lipid peroxidation, ROS, and glutathione redox status of skeletal muscle. The results showed that treatments with diazoxide and exercise at different intensities improved muscle contraction capacity by reducing oxidative stress during obesity, with the best results being obtained with low-intensity exercise in combination with diazoxide. Therefore, these results suggest that diazoxide and low-intensity exercise improve muscle function during obesity by decreasing oxidative stress with the same efficiency as a moderate-intensity exercise protocol.
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Oxidative stress is a factor that contributes to the development of complications in diabetes; however, its effects can be counteracted using exogenous antioxidants that are found in some plants, which is why people turn to traditional medicines in the search for therapeutic treatment. Justicia spicigera has been demonstrated to have the capacity to reduce glycemic levels; however, its effects on non-insulin-dependent organs such as the liver have not been reported. During 30 days of administration of Justicia spicigera ethanol extract, the blood glucose and weight of rats were measured every 5 days. Once the treatment was concluded, the rats were sacrificed. Corporal weight, blood glucose, cholesterol, very-low-density lipoprotein (VLDL), triglycerides, total lipids, and liver profile were reduced in the diabetic condition and normalized with the application of ethanol extract from J. spicigera (EJS). Additionally, there was a significant increase in catalase and superoxide dismutase activity in the control diabetic rats, a decrease in their activity with the extract administration, and no effect on normoglycemic rats. In conclusion, EJS is considered to be capable of reducing oxidative stress by maintaining diminished lipid and liver function profiles in male Wistar rats with streptozotocin-induced diabetes.
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Diabetes Mellitus Experimental , Justicia , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Glicemia , Diabetes Mellitus Experimental/tratamento farmacológico , Etanol/farmacologia , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Masculino , Estresse Oxidativo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , EstreptozocinaRESUMO
In the present study, we used a by-product from Agave lechuguilla (guishe) to test its antidiabetic effect, hypolipidemic activity, and capacity to mitigate the oxidative stress in kidney mitochondria from streptozotocin-induced diabetic rats. Orally, a crude aqueous extract from lyophilized guishe was administered over 5 weeks at different doses. Blood glucose and body weight were monitored. Also, blood chemistry, bilirubin, and alanine aminotransferase were assayed. Furthermore, the activity of catalase, thiobarbituric acid reactive species, mitochondrial superoxide dismutase, glutathione and glutathione peroxidase were determined in isolated kidney mitochondria. Our results show that guishe extracts have no antidiabetic properties at any dose. Nevertheless, it was able to diminish serum triglyceride levels and regulate the oxidative stress observed in isolated kidney mitochondria. These observations indicate that the aqueous extract from guishe can be used to treat abnormalities in serum lipids, as a hypolipidemic, and mitigate the oxidative stress, as an antioxidant, occurring during diabetes.
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Diabetes mellitus (DM) constitutes one of the public health problems today. It is characterized by hyperglycemia through a defect in the ß-cells function and/or decreased insulin sensitivity. Apocynin has been tasted acting directly as an NADPH oxidase inhibitor and reactive oxygen species (ROS) scavenger, exhibiting beneficial effects against diabetic complications. Hence, the present study's goal was to dissect the possible mechanisms by which apocynin could mediate its cardioprotective effect against DM-induced oxidative stress. Male Wistar rats were assigned into 4 groups: Control (C), control + apocynin (C+A), diabetes (D), diabetes + apocynin (D+A). DM was induced with streptozotocin. Apocynin treatment (3 mg/kg/day) was applied for 5 weeks. Treatment significantly decreased blood glucose levels and insulin resistance in diabetic rats. In cardiac tissue, ROS levels were higher, and catalase enzyme activity was reduced in the D group compared to the C group; the apocynin treatment significantly attenuated these responses. In heart mitochondria, Complexes I and II of the electron transport chain (ETC) were significantly enhanced in the D+A group. Total glutathione, the level of reduced glutathione (GSH) and the GSH/ oxidized glutathione (GSSG) ratio were increased in the D+A group. Superoxide dismutase (SOD) and the glutathione peroxidase (GSH-Px) activities were without change. Apocynin enhances glucose uptake and insulin sensitivity, preserving the antioxidant defense and mitochondrial function.
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Gestational diabetes (GD) has a negative impact on neurodevelopment, resulting in cognitive and neurological deficiencies. Oxidative stress (OS) has been reported in the brain of the first-generation offspring of GD rats. OS has been strongly associated with neurodegenerative diseases. In this work, we determined the effect of GD on the cognitive behavior, oxidative stress and metabolism of second-generation offspring. GD was induced with streptozotocin (STZ) in pregnant rats to obtain first-generation offspring (F1), next female F1 rats were mated with control males to obtain second-generation offspring (F2). Two and six-month-old F2 males and females were employed. Anxious-type behavior, spatial learning and spatial working memory were evaluated. In cerebral cortex and hippocampus, the oxidative stress and serum biochemical parameters were measured. Male F2 GD offspring presented the highest level of anxiety-type behavior, whilst females had the lowest level of anxiety-type behavior at juvenile age. In short-term memory, adult females presented deficiencies. The offspring F2 GD females presented modifications in oxidative stress biomarkers in the cerebral cortex as lipid-peroxidation, oxidized glutathione and catalase activity. We also observed metabolic disturbances, particularly in the lipid and insulin levels of male and female F2 GD offspring. Our results suggest a transgenerational effect of GD on metabolism, anxiety-like behavior, and spatial working memory.
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Ansiedade/etiologia , Comportamento Animal/fisiologia , Fenômenos Fisiológicos da Nutrição Materna , Estresse Oxidativo/fisiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Animais , Biomarcadores , Córtex Cerebral/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/psicologia , Diabetes Gestacional/metabolismo , Diabetes Gestacional/psicologia , Modelos Animais de Doenças , Feminino , Hipocampo/metabolismo , Peroxidação de Lipídeos/fisiologia , Masculino , Memória de Curto Prazo/fisiologia , Gravidez , Ratos , Aprendizagem Espacial/fisiologia , EstreptozocinaRESUMO
Diabetes mellitus is characterized by chronic hyperglycemia causing mitochondrial dysfunction and kidney iron overload has been observed during diabetes. We evaluated the effects of an iron-restricted diet (IRD) on mitochondrial function, oxidative stress, and mitochondrial iron levels in the kidneys of Wistar rats with streptozotocin-induced diabetes. IRD ameliorated mitochondrial dysfunction in diabetic rats by restoring mitochondrial respiration and respiratory complex activity, improving oxidative stress and glutathione status in kidney mitochondria. We also observed mitochondrial iron overload. Our data suggest that elevated iron levels were attenuated by IRD, resulting in modulation of oxidative stress and mitochondrial function in the kidney.
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Diabetes Mellitus Experimental/dietoterapia , Ferro/metabolismo , Mitocôndrias/metabolismo , Animais , Respiração Celular , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Glutationa/metabolismo , Deficiências de Ferro , Ferro da Dieta , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Estreptozocina , Resultado do TratamentoRESUMO
Abnormalities in lipid metabolism, associated with increased risk of cardiovascular disease (CVD), frequently occur in people with diabetes. Eryngium carlinae is a plant used in traditional medicine to treat lipid abnormalities. The chemical composition and hypolipidemic activity of the ethanolic extract of E. carlinae were analyzed to broaden our knowledge of its mechanism of action. The ethanolic extract of E. carlinae was tested for hypolipidemic activity by oral administration for 40 days. Atorvastatin, a widely used statin, was also administered to compare its effect with that of the extract. Serum was used for analysis of the lipid profile and liver microsomes to assess 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and low-density lipoprotein receptor (LDL-r) levels. The extract was able to reduce total cholesterol and non-high-density lipoprotein cholesterol (C-HDL) levels and increase the C-HDL levels reduced in diabetes, decreasing the atherogenic index and therefore the risk of suffering CVD at the same level as atorvastatin. The HMG-CoA reductase activity and LDL-r levels were not modified by the administration of E. carlinae. The results demonstrate the hypolipidemic potential of ethanol extract of E. carlinae and support its use in traditional medicine as a hypolipidemic agent.
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Diabetes Mellitus Experimental/tratamento farmacológico , Eryngium/química , Hipolipemiantes/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Atorvastatina , Colesterol/sangue , Etanol , Hidroximetilglutaril-CoA Redutases/metabolismo , Lipídeos/sangue , Microssomos Hepáticos/enzimologia , Ratos , Ratos WistarRESUMO
Gestational diabetes (GD) has been linked with an increased risk of developing metabolic disorders and behavioral abnormalities in the offspring. Oxidative stress is strongly associated with neurodegeneration and cognitive disruption. In the offspring brains in a GD experimental rat model, increased oxidative stress in the prenatal and postnatal stages was reported. However, long-term alterations to offspring behavior and oxidative stress, caused by changes in the cerebral cortex and hippocampus, remain unclear. In this study, we evaluated the effect of GD on young and adult male and female rat offspring in metabolic parameters, cognitive behavior, and oxidative stress. GD was induced using streptozotocin in dams. Next, the offspring were evaluated at two and six months of age. Anxiety-like behavior was evaluated using the elevated plus maze and open field maze; spatial learning and short-term memory were evaluated using the Morris water maze and radial maze, respectively. We determined oxidative stress biomarkers (reactive oxygen species (ROS), lipid peroxidation and glutathione status) and antioxidant enzymes (superoxide dismutase and catalase) in the brain of offspring. We observed that male GD offspring showed a reduced level of anxiety at both ages as they spent less time in the closed arms of the elevated plus maze at adult age ((P = 0.019, d = 1.083 ( size effect)) and spent more time in the open area of an open field (P = 0.0412, d = 0.743) when young and adult age (P = 0.018, d = 0.65). Adult female GD offspring showed a reduced level of anxiety (P = 0.036; d = 0.966), and young female GD offspring showed a deficiency in spatial learning (P = 0.0291 vs. control, d = 3.207). Adult male GD offspring showed a deficiency in short-term memory (P = 0.017, d = 1.795). We found an increase in ROS and lipid peroxidation, a disruption in the glutathione status, and decreased activity of catalase and superoxide dismutase (P < 0.05 vs. control, d > 1.0), in the cerebral cortex and hippocampus of male and female GD offspring. GD altered metabolism; male offspring of both ages and adult females showed a high level of triglycerides and a lower level of high-density lipoprotein-cholesterol (P < 0.05 vs. control, d > 1.0). Young and adult female offspring displayed higher insulin levels (P < 0.05, d > 1.0). These results suggest that gestational diabetes modifies oxidative stress and cognitive behavior in an age- and sex-dependent manner.
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Antioxidantes/metabolismo , Ansiedade , Encéfalo/metabolismo , Cognição , Diabetes Gestacional , Aprendizagem , Estresse Oxidativo , Animais , Catalase/metabolismo , Córtex Cerebral/metabolismo , HDL-Colesterol/sangue , Diabetes Gestacional/metabolismo , Feminino , Glutationa/metabolismo , Hipocampo/metabolismo , Peroxidação de Lipídeos , Masculino , Aprendizagem em Labirinto , Memória de Curto Prazo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/psicologia , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Triglicerídeos/sangueRESUMO
In the present study, we investigated the composition and antioxidant activity of the hexanic extract of Eryngium carlinae inflorescences by employing in vitro assays to measure antioxidant capacity and 2,2-diphenyl-1-picrylhydrazyl scavenging activity. We also applied the hexanic extract to Saccharomyces cerevisiae, under hydrogen peroxide-induced stress. Finally, we tested the extract in male Wistar rats with and without streptozotocin-induced diabetes. The compounds in the hexanic extract were analyzed by gas-chromatography-mass spectrometry, which revealed mainly terpenes and sesquiterpenes, including (Z)ß-farnesene (38.79%), ß-pinene (17.53%), calamene (13.3%), and α-farnesene (10.38%). In vitro and in S. cerevisiae, the extract possessed antioxidant activity at different concentrations, compared to ascorbic acid (positive control). In normoglycemic and hyperglycemic rats, oral administration of 30 mg/kg of the extract reduced blood glucose levels; lipid peroxidation in liver, kidney and brain; protein carbonylation; and reactive oxygen species (ROS) production. It also increased catalase activity in the brain, kidneys and liver. These findings show that this hexanic extract of E. carlinae inflorescences possessed antioxidant properties.