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High-fat and high-carbohydrate (HF-HC) diets induce metabolic syndrome via mitochondrial dysfunction and oxidative stress. We have previously shown that this may be prevented by avocado oil, a source of bioactive molecules with antioxidant properties. However, it is unknown if these effects are mediated by the unsaponifiable fraction of avocado oil (UFAO). Thus, we tested if this fraction improves glucose metabolism, bioenergetics and oxidative stress in mitochondria from the kidney and liver of rats fed an HF-HC diet. We found that 12 weeks of an HF-HC diet impaired glucose utilization and increased insulin resistance, which was prevented by UFAO administration. The HF-HC diet decreased respiration, membrane potential and electron transport chain (ETC) function in liver and kidney mitochondria. These mitochondrial dysfunctions were prevented by UFAO intake. Unexpectedly, UFAO increased ROS levels in the mitochondria of control animals and did not decrease them in rats with an HF-HC diet; however, UFAO protects liver and kidney mitochondria from iron-induced oxidative stress. These findings suggest that impairments in glucose metabolism and mitochondrial function by an HF-HC diet may be prevented by UFAO, without decreasing ROS generation but protecting mitochondria from oxidative damage.
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High-saturated fat (HF) or high-fructose (HFr) consumption in children predispose them to metabolic syndrome (MetS). In rodent models of MetS, diets containing individually HF or HFr lead to a variable degree of MetS. Nevertheless, simultaneous intake of HF plus HFr have synergistic effects, worsening MetS outcomes. In children, the effects of HF or HFr intake usually have been addressed individually. Therefore, we have reviewed the outcomes of HF or HFr diets in children, and we compare them with the effects reported in rodents. In humans, HFr intake causes increased lipogenesis, hypertriglyceridemia, obesity and insulin resistance. On the other hand, HF diets promote low grade-inflammation, obesity, insulin resistance. Despite the deleterious effects of simultaneous HF plus HFr intake on MetS development in rodents, there is little information about the combined effects of HF plus HFr intake in children. The aim of this review is to warn about this issue, as individually addressing the effects produced by HF or HFr may underestimate the severity of the outcomes of Western diet intake in the pediatric population. We consider that this is an alarming issue that needs to be assessed, as the simultaneous intake of HF plus HFr is common on fast food menus.
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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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A molecular switch based on the metastable radical anion derived from a substituted heteroaryl quinone is described. Pyrrolyl quinone thiocyanate (PQ 9) showed an interaction with the fluoride anion that was visible to the naked eye and quantified by UV/vis and 1H and 13â C NMR. The metastable quinoid species formed by the interaction with F- ("ON" state) showed a molecular switching effect autocontrolled by the presence of ascorbate ("OFF" state) and back to the "ON" state by an autooxidation process, measured by visible and UV/vis spectroscopy. Due to its out-of-equilibrium properties and the exchange of matter and energy, a dissipative structural behaviour is proposed. Considering its similarity to the mechanism of coenzyme Q in oxidative phosphophorylation, PQ 9 was evaluated on Saccharomyces cerevisiae mitochondrial function for inhibition of complexes II, III and IV, reactive oxygen species (ROS) production, catalase activity and lipid peroxidation. The results showed that PQ 9 inhibited complex III activity as well as the activity of all electron transport chain (ETC) complexes. In addition, PQ 9 reduced ROS production and catalase activity in yeast. The results suggest that PQ 9 may have potential applications as a new microbicidal compound by inducing ETC dysfunction.
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High sodium intake is decisive in the incidence increase and prevalence of hypertension, which has an impact on skeletal muscle functionality. Diazoxide is an antihypertensive agent that inhibits insulin secretion and is an opener of KATP channels (adosine triphosphate sensitive potasium channels). For this reason, it is hypothesized that moderate-intensity exercise and diazoxide improve skeletal muscle function by reducing the oxidants in hypertensive rats. Male Wistar rats were assigned into eight groups: control (CTRL), diazoxide (DZX), exercise (EX), exercise + diazoxide (EX + DZX), hypertension (HTN), hypertension + diazoxide (HTN + DZX), hypertension + exercise (HTN + EX), and hypertension + exercise + diazoxide (HTN + EX + DZX). To induce hypertension, the rats received 8% NaCl dissolved in water orally for 30 days; in the following 8 weeks, 4% NaCl was supplied to maintain the pathology. The treatment with physical exercise of moderate intensity lasted 8 weeks. The administration dose of diazoxide was 35 mg/kg intraperitoneally for 14 days. Tension recording was performed on the extensor digitorum longus and the soleus muscle. Muscle homogenates were used to measure oxidants using fluorescent probe and the activity of antioxidant systems. Diazoxide and moderate-intensity exercise reduced oxidants and increased antioxidant defenses.
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Antioxidantes , Diazóxido , Hipertensión , Músculo Esquelético , Condicionamiento Físico Animal , Ratas Wistar , Animales , Diazóxido/farmacología , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Hipertensión/metabolismo , Hipertensión/fisiopatología , Condicionamiento Físico Animal/fisiología , Ratas , Antioxidantes/metabolismo , Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Oxidantes/metabolismoRESUMEN
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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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 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 del Metal , Ratas , Animales , Antioxidantes/farmacología , Antioxidantes/metabolismo , Estreptozocina/metabolismo , Estreptozocina/farmacología , Estreptozocina/uso terapéutico , Eryngium/metabolismo , Plata/farmacología , Plata/metabolismo , Plata/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Estrés Oxidativo , Ratas Wistar , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Peroxidación de Lípido , Encéfalo/metabolismo , Mitocondrias/metabolismoRESUMEN
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 , Hiperglucemia , Ratones , Ratas , Animales , Diazóxido/efectos adversos , Diazóxido/metabolismo , Estreptozocina/efectos adversos , Estreptozocina/metabolismo , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Diabetes Mellitus Experimental/complicaciones , Sustancias Reactivas al Ácido Tiobarbitúrico/efectos adversos , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Estrés Oxidativo , Hiperglucemia/complicaciones , Músculo Esquelético/metabolismo , Lípidos , Triglicéridos/efectos adversos , Triglicéridos/metabolismo , Colesterol/metabolismoRESUMEN
Gallic (GA) and ellagic (EA) acids are present in foods, medicinal plants, teas, and dietary supplements. An acute toxicological study was conducted by oral administration of both compounds alone (200, 1000, and 2000 mg/kg) and combined (2000 mg/kg) and their effects on the electron transport chain (ETC) and the ROS production in kidney mitochondria further evaluated. All treatments induced a dose-dependent heart, lung, and kidney injury. However, the intensity of these effects varied according to the substance, with greater cardiac and renal toxicity for EA and pulmonary injury for GA, while the combination attenuated the toxicity of the isolated molecules. All substances inhibited the activity of complexes II, III, and IV of the ETC from renal mitochondria. However, no changes were observed regarding mitochondrial ROS production. These compounds have a non-negligible inherent deleterious potential, so their uncontrolled use at high doses (≥200 mg/kg) could cause undesirable effects.
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Ácido Gálico , Lesiones Cardíacas , Ratas , Animales , Ratas Wistar , Ácido Gálico/farmacología , Especies Reactivas de Oxígeno , Ácido Elágico/farmacología , Riñón , Pulmón , Administración OralRESUMEN
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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Polyunsaturated fatty acids (PUFA) hypersensitize yeast to oxidative stress. Ethanol accumulation during fermentation is another factor that induces oxidative stress via mitochondrial dysfunction and ROS overproduction. Since this microorganism has raised growing interest as a PUFA factory, we have studied if the combination of PUFA plus ethanol enhances yeast death. Respiration, ROS generation, lipid peroxidation, mitochondrial cardiolipin content, and cell death were assessed in yeast grown in the presence of 10% ethanol (ETOH) or linolenic acid (C18:3), or ethanol plus C18:3 (ETOH+C18:3). Lipid peroxidation and cardiolipin loss were several-fold higher in cells with ETOH+C18:3 than with C18:3. On the contrary, ETOH tended to increase cardiolipin content without inducing changes in lipid peroxidation. This was consistent with a remarkable diminution of cell growth and an exacerbated propidium iodide staining in cells with only ETOH+C18:3. The respiration rate decreased with all the treatments to a similar degree, and this was paralleled with similar increments in ROS between all the treatments. These results indicate that PUFA plus ethanol hypersensitize yeast to necrotic cell death by exacerbating membrane damage and mitochondrial cardiolipin loss, independent of mitochondrial dysfunction and ROS generation. The implications of these observations for some biotechnological applications in yeast and its physiology are discussed.
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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 , Género Justicia , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Glucemia , Diabetes Mellitus Experimental/tratamiento farmacológico , Etanol/farmacología , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Masculino , Estrés Oxidativo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Ratas Wistar , EstreptozocinaRESUMEN
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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Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in hepatocytes, and in advanced stages, by inflammation and fibrosis. Excessive ROS production due to mitochondrial dysfunction contributes to NAFLD development, making the decrease in mitochondrial ROS production an emerging target to alleviate NAFLD. Previously, we have shown that avocado oil, a source of several bioactive compounds with antioxidant effects, decreases oxidative stress by improving the function of the mitochondrial electron transport chain (ETC) and decreasing ROS levels in mitochondria of diabetic and hypertensive rats. Therefore, we tested in this work whether avocado oil alleviates NAFLD by attenuating mitochondrial dysfunction, oxidative stress and inflammation. NAFLD was induced in rats by a high fat-high fructose (HF) diet administered for six (HF6) or twelve (HF12) weeks. Hepatic steatosis, hypertrophy and inflammation were detected in both the HF6 and HF12 groups. Hyperglycemia was observed only in the HF12 group. The HF6 and HF12 groups displayed dyslipidemia, impairments in mitochondrial respiration, complex III activity, and electron transfer in cytochromes in the complex III. This led to an increase in the levels of ROS and lipid peroxidation. The substitution of the HF6 diet by standard chow and avocado oil for 6 weeks (HF6+AVO + D), or supplementation of the HF12 diet with avocado oil (HF12 + AVO), ameliorated NAFLD, hyperglycemia, dyslipidemia, and counteracted mitochondrial dysfunctions and oxidative stress. The substitution of the HF6 diet by standard chow without avocado oil did not correct many of these abnormalities, confirming that the removal of the HF diet is not enough to counteract NAFLD and mitochondrial dysfunction. In summary, avocado oil decreases NAFLD by improving mitochondrial function, oxidative stress, and inflammation.
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Hypertension impairs the function of the kidney and its vasculature. Adrenergic activation is involved in these processes by promoting oxidative stress and mitochondrial dysfunction. Thus, the targeting of mitochondrial function and mitochondrial oxidative stress may be an approach to alleviate hypertensive kidney damage. Avocado oil, a source of oleic acid and antioxidants, improves mitochondrial dysfunction, decreases mitochondrial oxidative stress, and enhances vascular function in hypertensive rats. However, whether avocado oil improves the function of renal vasculature during the adrenergic stimulation, and if this is related to improvement in renal damage and enhancement of mitochondrial activity is unknown. Thus, the effects of avocado oil on renal vascular responses to adrenergic stimulation, mitochondrial dysfunction, oxidative stress, and renal damage were compared with prazosin, an antagonist of α1-adrenoceptors, in hypertensive rats induced by L-NAME. Avocado oil or prazosin decreased blood pressure, improved endothelium-dependent renal vasodilation, prevented mitochondrial dysfunction and kidney damage in hypertensive rats. However, avocado oil, but not prazosin, decreased mitochondrial ROS generation and improved the redox state of mitochondrial glutathione. These results suggest that avocado oil and prazosin prevented hypertensive renal damage due to the improvement in 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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Ansiedad/etiología , Conducta Animal/fisiología , Fenómenos Fisiologicos Nutricionales Maternos , Estrés Oxidativo/fisiología , Efectos Tardíos de la Exposición Prenatal/etiología , Animales , Biomarcadores , Corteza Cerebral/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/psicología , Diabetes Gestacional/metabolismo , Diabetes Gestacional/psicología , Modelos Animales de Enfermedad , Femenino , Hipocampo/metabolismo , Peroxidación de Lípido/fisiología , Masculino , Memoria a Corto Plazo/fisiología , Embarazo , Ratas , Aprendizaje Espacial/fisiología , EstreptozocinaRESUMEN
Glutathione peroxidase 4 (Gpx4) counteracts mitochondrial lipid peroxidation in mammals. In yeast, Gpx2 is orthologous of Gpx4, is localized in mitochondria, and reduces both inorganic and organic peroxides. However, a phenotype of oxidative stress hypersensitivity has not been observed with gpx2 deletion. We hypothesized that the absence of polyunsaturated fatty acids (PUFA) in yeast membranes may mask an antioxidant role of Gpx2 in mitochondria. Thus, we tested the effects of PUFA on cell viability, mitochondrial function, ROS production, and mitochondrial fatty acid composition of a gpx2Δ mutant subjected to chronological aging. As expected, gpx2Δ mutation did not alter these parameters with respect to wild-type (WT) cells after 30 h growth, even in the presence of linolenic acid (C18:3), except for some activities of the electron transport chain (ETC) complexes. Conversely, aged gpx2Δ cells exhibited lower viability, impaired respiration, decreased ETC activities, and increased ROS generation in comparison to aged WT cells. These effects were exacerbated by C18:3, as gpx2Δ cells displayed residual respiration, full inhibition of ETC complexes, and a burst in ROS production on day 15 that decreased on day 30, although ROS remained several-fold higher than in WT cells. gpx2 was not involved in the preservation of PUFA levels, as no differences in mitochondrial C18:3 content were observed between WT and gpx2Δ cells. These results indicate that gpx2 is a late - acting antioxidant system that decreases mitochondrial ROS production and preserves ETC function, without being involved in the preservation of PUFA levels in mitochondria.