Stress In Rat Liver Mitochondria Research Articles

Effects of Dihydroquercetin on the Intensity of Oxydative Stress in Rat Liver Mitochondria at Hypothermia

A decrease in body temperature in homeothermic animals can cause a state of the body called hypothermic. It is accompanied by the development of a number of pathological processes, many of which are associated with mitochondrial dysfunction and the development of oxidative stress. In connection with the widespread introduction of hypothermia into medical practice, the question of the possibility of a regulatory influence on the proxidant-antioxidant status of mitochondria at low body temperatures remains relevant. In recent years, plant polyphenols, in particular dihydroquercetin (DHQ), have gained wide popularity as therapeutic agents with antioxidant and membrane protective effects. In this work, we investigated the effects of DHQ on the intensity of oxidative stress in rat liver mitochondria under moderate hypothermia. It was found that a course (5 days) oral administration of DHA at a dose of 100 mg/kg significantly reduces the levels of LPO and OMP products in the liver mitochondria of control rats, increasing the content of non-enzymatic components of the thiol-disulfide antioxidant system`s. DHQ effectively protects liver mitochondria from the development of oxidative stress during hypothermia, as evidenced by a significant decrease (and in some cases, complete normalization) in the levels of diene conjugates, MDA, Schiff bases and carbonyl groups in a group of animals subjected to hypothermia with prior administration of this polyphenol. At the same time, DHQ significantly increases the levels of glutathione and vitamin E, and also normalizes the content of thiol groups in mitochondrial proteins. In vitro, DHQ exhibits a dose-dependent antioxidant effect, suppressing OMB in mitochondria incubated in Fenton's medium (IC50 = 0.160 mg/ml).

Effects of Dihydroquercetin on the Intensity of Oxydative Stress in Rat Liver Mitochondria at Hypothermia

Effects of Dihydroquercetin on the Intensity of Oxydative Stress in Rat Liver Mitochondria at Hypothermia

Ethyl acetate extract of Terminalia arjuna bark shows antioxidant activity and protects against oxidative stress in rat liver mitochondria

The antioxidant properties of Terminalia arjuna (TA) bark have been identified in this present study. The antioxidant properties of ethyl acetate extract of TA bark were established by DPPH radical scavenging activity, reducing power, H2O2 scavenging activity, scavenging activity of hydroxyl radical, superoxide radical, and nitric oxide radical. This present study also showed the protective effects of ethyl acetate extract against copper-ascorbate-induced oxidative stress in rat liver mitochondria in vitro. The ethyl acetate extract of TA barkaltered the content of reduced glutathione (GSH), levels of lipid-peroxidation (LPO), and protein carbonylation (PCO) (P<0.001) against copper-ascorbate treated rat liver mitochondria, in vitro. Thus, the results indicate that the ethyl acetate extract of TA bark can be considered as a therapeutic agent in the future.

Folate- and glucuronate–functionalization of layered double hydroxides containing dysprosium and gadolinium and the effect on oxidative stress in rat liver mitochondria

Zinc/aluminum layered double hydroxide (LDH) particles were prepared by alkaline precipitation in the presence of dysprosium and dysprosium/gadolinium cations. The particles formed were stable against exchange reactions with folate or glucuronate ions since these organic ions exclusively functionalized the external surface of the layered double hydroxides. While the dysprosium derivatives reached magnetization susceptibilities between 2.06 × 10−5 and 2.20 × 10−5 cm3/g, the samples simultaneously containing dysprosium and gadolinium decreased to a range between 1.08 × 10−5 and 1.73 × 10−5 cm3/g. This last sample was tested as a magnetic resonance imaging contrast agent and demonstrated a reduction in T1 and T2 relaxation times in a linear dependence with the LDH concentration. The oxidative stress assays in rat liver mitochondria demonstrated the low toxicity of the composition simultaneously containing dysprosium and gadolinium as well as the functionalization product with glucuronate ions, suggesting the potential of these particles to design alternative MRI contrast agents.

Purified Acetaminophen-Glutathione Conjugate Is Able To Induce Oxidative Stress in Rat Liver Mitochondria

Acetaminophen overdose is the most often cause of acute liver injury. The toxic mechanism is linked to formation of an active metabolite that reacts with glutathione generating acetaminophen-glutathione conjugate (APAP-SG). This compound has been recognized to be non-toxic generally. Our preliminary results showed, however, that APAP-SG could possess a toxic effect too. Therefore, the aim of our study was to prepare, purify and to test possible toxicity of APAP-SG. We prepared APAP-SG using organic synthesis. The conjugate was purified by preparative HPLC and its structure was confirmed using mass spectrometry. Final purity of APAP-SG was >98 %. We estimated a toxic effect of APAP-SG in isolated rat liver mitochondria using a fluorescent ROS probe. We assessed ROS production in presence of complex I or complex II substrates. The increase of ROS-dependent fluorescence in presence of glutamate/malate was 104 ± 13 % and 130 ± 10 % in 1 mM and 5 mM APAP-SG, respectively, in comparison with controls. ROS production related to presence of complex II substrate was enhanced 4-times in APAP-SG (5 mM) treated mitochondria (compared to controls). We conclude, we proved our hypothesis that APAP-SG conjugate is able to induce a mitochondrial impairment leading to enhanced ROS production.

Mitochondrial oxidative stress induced by Ca2+ and monoamines: different behaviour of liver and brain mitochondria in undergoing permeability transition

Mitochondrial permeability transition (MPT) is correlated with the opening of a nonspecific pore, the so-called transition pore, that triggers bidirectional traffic of inorganic solutes and metabolites across the mitochondrial membrane. This phenomenon is caused by supraphysiological Ca(2+) concentrations and by other compounds leading to oxidative stress, while cyclosporin A, ADP, bongkrekic acid, antioxidant agents and naturally occurring polyamines strongly inhibit it. The effects of polyamines, including the diamine agmatine, have been widely studied in several types of mitochondria. The effects of monoamines on MPT have to date, been less well-studied, even if they are involved in a variety of neurological and neuroendocrine processes. This study shows that in rat liver mitochondria (RLM), monoamines such as tyramine, serotonin and dopamine amplify the swelling induced by calcium, and increase the oxidation of thiol groups and the production of hydrogen peroxide, effects that are counteracted by the above-mentioned inhibitors. In rat brain mitochondria (RBM), the monoamines do not amplify calcium-induced swelling, even if they demonstrate increases in the extent of oxidation of thiol groups and hydrogen peroxide production. In these mitochondria, the antioxidants are not at all or scarcely effective in suppressing mitochondrial swelling. In conclusion, we hypothesize that different mechanisms induce the MPT in the two different types of mitochondria evaluated. Calcium and monoamines induce oxidative stress in RLM, which in turn appears to induce and amplify MPT. This process is not apparent in RBM, where MPT seems resistant to oxidative stress.

Beneficial effect of the administration of Hemidesmus indicus against bromobenzene induced oxidative stress in rat liver mitochondria

Aim of the study To study the beneficial effect of the prior administration of an aqueous extract of Hemidesmus indicus against bromobenzene induced oxidative damage in rat liver mitochondria. Materials and methods Oxidative stress was induced in rats with bromobenzene (10 mmol/kg body wt.). The rate of respiration, P/O ratios, lipid peroxides, protein carbonyls and sulphydryls were studied. Results When the rats were administered with bromobenzene, the rate of respiration was decreased significantly and the P/O ratio was completely abolished. There was a significant increase on the levels of lipid peroxide and protein carbonyl and a significant decrease on total sulphydryl groups when compared with control. Administration of rats with an aqueous extract (100 mg/kg) prior to bromobenzene administration showed significant beneficial effects like, stimulation in respiration, prevented the rise in lipid peroxides and protein carbonyls, increased the level of sulphydryl groups back to control level. Administration of vitamin E could not reverse as effectively as Hemidesmus indicus. Conclusions This study demonstrates a good protective effect of Hemidesmus indicus against the bromobenzene induced oxidative stress.

Short-term vitamin A supplementation at therapeutic doses induces a pro-oxidative state in the hepatic environment and facilitates calcium-ion-induced oxidative stress in rat liver mitochondria independently from permeability transition pore formation

There is a growing body of evidence showing that vitamin A induces toxic effects in several experimental models and in human beings. In the present work, we have investigated the effects of short-term vitamin A supplementation on the adult rat liver redox status. We have found that vitamin A at therapeutic doses induces a hepatic oxidative insult. Furthermore, we have observed increased antioxidant enzyme activity in the liver of vitamin-A-treated rats. Additionally, some mitochondrial dysfunction was found since superoxide anion production was increased in vitamin-A-treated rat liver submitochondrial particles, which may be the result of impaired mitochondrial electron transfer chain activity, as assessed here. We have also isolated rat liver mitochondria and challenged it with 75 muM CaCl2, a non-oxidant agent that is able to induce mitochondrial oxidative stress indirectly. We have found that mitochondria isolated from vitamin-A-treated rat liver are more sensitive to CaCl2 than control mitochondria regarding the redox status. Importantly, vitamin A seems to alter mitochondrial redox status independently of the participation of the mitochondrial permeability transition pore, which is activated by Ca2+ ions since cyclosporin A did not prevent the oxidative insult elicited by Ca2+ addition. Overall, we show here that mitochondria are a target of vitamin-A-associated toxicity also in vivo.

Effects of perinatal and maintained calorie restriction to mitochondrial level of oxidative stress in rat liver

Calorie restriction (CR) is known to extend the lifespan of a number of organisms including yeast, worms, flies, rodents and perhaps non‐human primates. The mechanisms through which occurs have been unclear. CR during gestation led to growth retardation at birth. If CR was prolonged throughout lactation, adult body weight was permanently reduced. There is also evidence that the intrauterine environment of the fetus may be of greater importance in the etiology of chronic diseases in adult fetus.The aim of this project is to determine the effect of a perinatal and maintained calorie restriction regimen in oxidative stress in rat liver mitochondria. Offsprings of one month of age showed a decreased in body weight of 48% in female and 56% in male rats. Levels of NO• in CR rats increased 180% in females and 282% in male rats compared to controls. Lipoperoxidation showed an increase of 211% in female and 116% in male rats under CR regimen against controls. Female and male rats of five months of age weighed 35% and 50%, respectively, less than controls. The determination of NO• shows a diminution of 56% in female and 36% in male rats under calorie restriction versus controls. The same can be seen in determination of lipoperoxidation with a diminution of a 54% in male rats but, in contrast, an increased in lipoperoxidation levels in female rats of 97% were observed versus controls. Our initial conclusion is that oxidative and nitrosative stresses are affected in offsprings of one month and in five month‐old. Supported by Fondos Mixtos CONACYT‐ Gob. Edo. de Michoacán (64277, 64308), COECYT and CIC‐UMSNH (2.16) grants.

Different behavior of agmatine in liver mitochondria: Inducer of oxidative stress or scavenger of reactive oxygen species?

Agmatine, at concentrations of 10 μM or 100 μM, is able to induce oxidative stress in rat liver mitochondria (RLM), as evidenced by increased oxygen uptake, H 2O 2 generation, and oxidation of sulfhydryl groups and glutathione. One proposal for the production of H 2O 2 and, most probably, other reactive oxygen species (ROS), is that they are the reaction products of agmatine oxidation by an unknown mitochondrial amine oxidase. Alternatively, by interacting with an iron–sulfur center of the respiratory chain, agmatine can produce an imino radical and subsequently the superoxide anion and other ROS. The observed oxidative stress causes a drop in ATP synthesis and amplification of the mitochondrial permeability transition (MPT) induced by Ca 2+. Instead, 1 mM agmatine generates larger amounts of H 2O 2 than the lower concentrations, but does not affect RLM respiration or redox levels of thiols and glutathione. Indeed, it maintains the normal level of ATP synthesis and prevents Ca 2+-induced MPT in the presence of phosphate. The self-scavenging effect against ROS production by agmatine at higher concentrations is also proposed.

Effect of graded corticosterone treatment on aging-related markers of oxidative stress in rat liver mitochondria

Caloric restriction (CR) decreases aging rate and lowers the rate of reactive oxygen species (ROS) production at mitochondria in different organs, but the signal responsible for this last change is unknown. Glucocorticoids could constitute such a signal since it is well known that their levels increase during CR, and available studies failed to find consistent effects of insulin, the other better described hormone that varies during CR, on mitochondrial oxidative stress. In addition, there is almost no information on the possible in vivo effects of glucocorticoids on specific markers of mitochondrial and tissue oxidative stress. In this investigation, male Wistar rats were treated with corticosterone at doses of 150 and 400 mg/kg of diet during 4 weeks. After that time, oxidative stress-related parameters were measured in the liver. The corticosterone treatments did not change the rate of ROS production or the rate of oxygen consumption of rat liver mitochondria. The two lipoxidation protein markers measured (malondialdehyde-lysine and carboxymethyllysine) were decreased by both corticosterone treatments. These changes were associated with decreases in fatty acid unsaturation, especially with lowered levels of the highly unsaturated araquidonic and docosahexaenoic acids, which decrease the sensitivity to lipid peroxidation processes. The specific protein carbonyl glutamic semialdehyde, a marker of protein oxidation, was also lowered at 400 mg/kg corticosterone. The protein glycoxydation marker carboxyethyllysine and the level of oxidative damage to mtDNA (8-oxo-7,8-dihydro-2 9-deoxyguanosine) were increased by corticosterone. The results do not support the idea that corticosterone is the signal responsible for the decrease in mitochondrial ROS generation during CR. However, they show that this hormone modulates the level of oxidative stress both in proteins and in mtDNA. Some of these changes can contribute to the chronic effects of the hormone at tissue level.

Effects of fasting on oxidative stress in rat liver mitochondria

While moderate caloric restriction has beneficial effects on animal health state, fasting may be harmful. The present investigation was designed to test how fasting affects oxidative stress, and to find out whether the effects are opposite to those previously found in caloric restriction studies. We have focused on one of the main determinants of aging rate: the rate of mitochondrial free radical generation. Different parameters related to lipid and protein oxidative damage were also analyzed. Liver mitochondria from rats subjected to 72 h of fasting leaked more electrons per unit of O2 consumed at complex III, than mitochondria from ad libitum fed rats. This increased leak led to a higher free radical generation under state 3 respiration using succinate as substrate. Regarding lipids, fasting altered fatty acid composition of hepatic membranes, increasing the double bond and the peroxidizability indexes. In accordance with this, we observed that hepatic membranes from the fasted animals were more sensitive to lipid peroxidation. Hepatic protein oxidative damage was also increased in fasted rats. Thus, the levels of oxidative modifications, produced either indirectly by reactive carbonyl compounds (Nepsilon- malondialdehyde-lysine), or directly through amino acid oxidation (glutamic and aminoadipic semialdehydes) were elevated due to the fasting treatment in both liver tissue and liver mitochondria. The current study shows that severe food deprivation increases oxidative stress in rat liver, at least in part, by increasing mitochondrial free radical generation during state 3 respiration and by increasing the sensitivity of hepatic membranes to oxidative damage, suggesting that fasting and caloric restriction have different effects on liver mitochondrial oxidative stress.

Metabolic changes induced by cold stress in rat liver mitochondria.

The mechanisms involved in the metabolic changes induced by cold stress in isolated rat liver mitochondria were studied. Respiration, ATP synthesis, and membrane potential as well as the contents of several metabolites were determined in liver mitochondria from cold-exposed rats. At different times of cold exposure, the force-flux relationships showed net variation in flux (enhanced respiration, diminished ATP synthesis) with no associated variation in force (H+ gradient); this suggested that decoupling rather than classical uncoupling was involved in the effects of cold stress. The flux control coefficient of the H+ leak on basal respiration was slightly increased by 380 h of cold exposure. Cold stress also induced a diminution in total membrane fatty acids, Zn2+, Fe3+, ATP, and ADP/O ratios; the content of cytochromes c + c1 and b oscillated. The contents of Ca2+, Na+, Pi, and cytochromes a + a3 were not affected, whereas matrix ADP, AMP, K+, and Mg2+ were markedly increased. Basal and oleic acid-stimulated respiration of mitochondria from cold-stressed rats was inhibited by GDP, carboxyatractyloside, or albumin. These agents did not affect basal respiration in control mitochondria. Western blot analysis showed enhanced expression of a protein of about 35 kDa, presumably the uncoupling protein 2, induced by long-term cold exposure. The overall data suggest that cold stress promoted decoupling of oxidative phosphorylation, and hence, changes in several matrix metabolites, by increasing free fatty acids and the UCP2 content.

Chronic ethanol feeding causes oxidative stress in rat liver mitochondria. Prevention by S-adenosyl methionine

Chronic ethanol feeding causes oxidative stress in rat liver mitochondria. Prevention by S-adenosyl methionine

Suppressive effects of retinoid on oxidative stress in rat liver mitochondria and ito cells

Suppressive effects of retinoid on oxidative stress in rat liver mitochondria and ito cells