Mitochondrial Malondialdehyde Research Articles

Modified Gegen Qinlian Decoction Ameliorates DSS-Induced Ulcerative Colitis in Mice by Inhibiting Ferroptosis via Nrf2/GPX4 Pathway

Objective. Ferroptosis, a form of programmed cell death, is considered a novel target for the treatment of ulcerative colitis (UC). The aim of this study was to explore whether modified Gegen Qinlian decoction (MGQD) ameliorates UC in mice via mediating ferroptosis. Methods. Mice with dextran sulfate sodium- (DSS-) induced colitis were administered with MGQD for seven days. Subsequently, iron, malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) were measured. ELISA and immunohistochemistry were used to evaluate the levels of proinflammatory cytokines and tight junction proteins, respectively. Transmission electron microscopy was used to reveal mitochondrial morphology. Western blot and qRT-PCR analyses were used to assess the expression levels of the proteins of Nrf2/GPX4 pathway. The docking affinity of MGQD and Nrf2 was assessed using AutoDock Vina 1.1.2. Results. Ferroptosis was identified in mice with UC, as demonstrated by mitochondrial disruption, MDA and ROS production, iron overload, decrease in GSH level, and abnormal expression of core marker proteins of ferroptosis. After MGQD treatment, these characteristic changes of ferroptosis were significantly reversed, along with concomitant activation of the Nrf2/GPX4 pathway. Furthermore, molecular docking analysis revealed that MGQD had a high affinity for Nrf2. Conclusion. MGQD may ameliorate UC by inhibiting ferroptosis via the activation of Nrf2/GPX4 pathway. This study provided new insights into the application of MGQD complementary therapy for UC.

ErZhiTianGui Decoction alleviates age-related ovarian aging by regulating mitochondrial homeostasis and inhibiting ferroptosis

AimThis study was designed to investigate the pharmacological effects and mechanisms of ErZhiTianGui Decoction (EZTG) for age-related ovarian aging in mice.MethodsThis study used naturally aging mice as a model, and EZTG was used for intragastric administration. Ovarian pathological changes, as well as follicular reserve were assessed by hematoxylin and eosin staining, and serum hormone levels (anti-mullerian hormone, follicle-stimulating hormone), mitochondrial reactive oxygen species (ROS) and mitochondrial DNA (mtDNA) damage marker 8-hydroxy-2′-deoxyguanosine(8-OHdG), and lipid peroxidation markers glutathione(GSH) and malondialdehyde(MDA) were determined by enzyme-linked immunosorbent assay. Mitochondrial membrane potential (MMP) levels in ovaries were determined using flow cytometry. The levels of PINK1 and Parkin were observed using immunofluorescence staining. Mitochondrial-derived vesicles (MDVs) and mitochondrial morphology were observed using electron microscopy. Prussian blue staining was used to observe iron ion aggregation in ovarian tissue. The Iron assay kits detected total iron levels. Western blot was used to detect the expression of proteins related to mitochondrial and ferroptosis related genes.ResultsAfter EZTG treatment, aged mice showed increased ovarian reserve, improved serum hormone levels, increased MMP, GSH levels, and decreased mitochondrial ROS, 8-OHdG, and MDA levels. Immunofluorescence staining showed decreased levels of PINK1 and Parkin, and the same trend was observed for the Western blot. Meanwhile, electron microscopy showed that EZTG improved the mitochondrial morphology in the ovaries of aged mice. EZTG also decreased the total iron and protein levels of Acyl-CoA synthetase long-chain family4 (ACSL4) and increased the protein level of glutathione peroxidase 4 (GPX4) in the ovaries of aged mice.ConclusionsEZTG can maintain PINK1/Parkin-mediated mitochondrial homeostasis, reduce the lipid peroxidation caused by the accumulation of ROS, and inhibit the occurrence of ferroptosis and delaying ovarian aging. These findings suggest that EZTG may be a promising drug for treating age-related ovarian aging in females.

Divergent Oxidative Stress in Normal Tissues and Inflammatory Cells in Hodgkin and Non-Hodgkin Lymphoma.

Previous studies reported mitochondrial and endoplasmic reticulum redox stress in peripheral blood mononucleated cells (PBMCs) of treatment-naïve Hodgkin lymphoma (HL) patients. Here, we assessed whether this response also applies to non-HL (NHL) patients, and whether the oxidative damage is a selective feature of PBMCs or, rather, also affects tissues not directly involved in the inflammatory response. Isolated PBMCs of 28 HL, 9 diffuse large B cell lymphoma, 8 less aggressive-NHL, and 45 controls underwent flow cytometry to evaluate redox stress and uptake of the glucose analogue 2-NBDG. This analysis was complemented with the assay of malondialdehyde (MDA) levels and enzymatic activity of glucose-6P-dehydrogenase and hexose-6P-dehydrogenase (H6PD). In all lymphoma patients, 18F-fluoro-deoxyglucose uptake was estimated in the myocardium and skeletal muscles. Mitochondrial reactive oxygen species generation and MDA levels were increased only in HL patients as well as H6PD activity and 2-NBDG uptake. Similarly, myocardial FDG retention was higher in HL than in other groups as opposed to a similar tracer uptake in the skeletal muscle. Redox stress of PBMCs is more pronounced in HL with respect to both NHL groups. This phenomenon is coherent with an increased activity of H6PD that also extends to the myocardium.

Influence mechanism of tempering for storage quality of dried rice based on the evaluation of physicochemical and sensory characteristics and mitochondrial function and structure

Use of tempering has proven to be effective for the improvement of rice milling quality, but few researches focused on its influence mechanism for dried rice storage quality. In this study, influence mechanism of tempering treatments [tempering at 65 °C (DTHT), 50 °C (DTMT) and no tempering (DTNT)] on the storage quality of two varieties rice (“Aolongsimiao” and “Shengtaiyou 018″) was evaluated based on the assessment of physicochemical and sensory quality, and a novel method judging the damage of mitochondrial function and structure in dried rice. During rice drying and storage, compared with DTNT and DTMT samples, DTHT samples showed the slowest increase in fatty acid value (FAV), nonanoic acid (off-flavor compound) content, cooked rice hardness, cross-sectional crack, and ratio of broken rice. DTHT samples suffered less oxidative damage, maintained significantly (p < 0.05) higher mitochondrial antioxidant capacities (MAC) and membrane integrity, and showed a less than 18.18% increase of mitochondrial malondialdehyde (MDA). Mitochondrial super oxide dismutase and MDA were significant correlation (p < 0.01) with moisture content, FAV, appearance, texture, comprehensive score, and stickiness of rice quality. Tempering influence mechanism for rice storage quality might be its maintaining MAC and membrane integrity, and then inhibiting the decrease of dried rice storage quality.

Exposure of combination of environmental pollutant, lead (Pb) and β-amyloid peptides causes mitochondrial dysfunction and oxidative stress in human neuronal cells.

Exposure to the environmental pollutant lead (Pb) has been linked to Alzheimer's disease (AD), in which mitochondrial dysfunction is a pathological consequence of neuronal degeneration. The toxicity of Pb in combination with β-amyloid peptides (1-40) and (25-35) causes selective death in neuronal cells. However, the precise mechanism through which Pb induces Alzheimer's disease, particularly mitochondrial damage, is unknown. Changes in mitochondrial mass, membrane potential, mitochondrial complex activities, mitochondrial DNA and oxidative stress were examined in neuronal cells of human origin exposed to Pb and β-amyloid peptides (1-40) and (25-35) individually and in different combinations. The results showed depolarization of mitochondrial membrane potential, decrease in mitochondrial mass, ATP levels and mtDNA copy number in Pb and β-amyloid peptides (1-40) and (25-35) exposed cells. Also, significant reductions in the expression of mitochondrial electron transport chain (ETC) complex proteins (ATP5A, COXIV, UQCRC2, SDHB, NDUFS3), as well as down regulation of ETC complex gene expressions such as COXIV, ATP5F1 and NDUFS3 and antioxidant gene expressions like MnSOD and Gpx4 were observed in exposed cells. Furthermore, Pb and β-amyloid peptides exposure resulted in elevated mitochondrial malondialdehyde levels and a decrease in mitochondrial GSH levels. Our findings suggest that Pb toxicity could be one of the causative factors for the mitochondrial dysfunction and oxidative stress in Alzheimer's disease progression.

Methanol fraction of Ficus mucoso (welw) prevents iron-induced oxidative damage and alters mitochondrial dysfunction in Drosophila melanogaster

The present study investigated the antioxidant and cyto-/mito-protective roles of Methanol Fraction of Ficus mucoso (MFFM) in iron-induced oxidative damage in Drosophila melanogaster. At first, 10-day survival rates were carried out separately on FeSO4 and MFFM, respectively, after which ameliorative effects of MFFM were investigated on FeSO4-induced toxicity for 5 days using biochemical and behavioral markers. Additionally, mitochondria were isolated from treated D. melanogaster to assess mitochondrial Permeability Transition (mPT) pore opening. The results showed that FeSO4 significantly reduced survival rate, total thiol level and activities of catalase and glutathione-S-transferase in D. melanogaster. In addition, treatment with FeSO4 caused increased generation of H2O2, NO (nitrite/nitrates) and acetylcholinesterase (AChE) activity compared with control (p < 0.05). Conversely, MFFM restored FeSO4-induced inhibition of glutathione-S-transferase and catalase activities, as well as glutathione and total thiol levels. FeSO4-induced elevation of AChE activity as well as H2O2 and NO (nitrites/nitrates) levels were ameliorated by MFFM with improved climbing activity. Interestingly, MFFM prevented FeSO4-induced mitochondrial Permeability Transition (mPT) pore opening, and elevated mitochondrial ATPase activity and mitochondrial lipid peroxides generation in D. melanogaster. Taken together, our results demonstrated that iron impaired anti-stress defence capacity, altered behavioral functions, increased generation of mitochondrial malondialdehyde and activated opening of the mPT pore in D. melanogaster. Conversely, methanol fraction of F. mucoso protected against iron-induced cyto-/mito-toxic effects. F. mucoso possibly contain bioactive agents which might be useful in the management of disorders associated with oxidative stress induced by iron and or related metals.

Selenium restores mitochondrial dysfunction to reduce Cr-induced cell apoptosis in Chinese cabbage (Brassica campestris L. ssp. Pekinensis) root tips

Chromium (Cr) disrupts the growth and physiology of plants. Selenium (Se) is considered as a promising option to help plants ameliorate Cr toxicity. To investigate the effects of exogenous Se on reactive oxygen species (ROS) burst and programmed cell death (PCD) in root tip cells under Cr stress, hydroponic experiments were carried out with Chinese cabbage seedlings grown in Hoagland solution containing 1 mg L-1 Cr and 0.1 mg L-1 Se. Results showed that Se scavenged the overproduction of H2O2 and O2－·, and alleviated the level of lipid peroxidation in root tips stressed by Cr. Moreover, Se effectively prevented DNA degradation and reduced the number of apoptotic cells in root tips. Compared with Cr treatment, Se supplementation reduced the content of ROS and malondialdehyde in mitochondria by 38.23% and 17.52%, respectively. Se application decreased the opening degree of mitochondrial permeability transition pores by 32.30%, increased mitochondrial membrane potential by 40.91%, alleviated the release of cyt c from mitochondria into cytosol by 18.42% and caused 57.40% decrease of caspase 3-like protease activity, and thus restored mitochondrial dysfunction caused by Cr stress. In addition, the alteration of Se on mitochondrial physiological properties maintained calcium homeostasis between mitochondria and cytosol, which further contributed to reducing the appearance of Cr-induced PCD. Findings suggested that Se restored mitochondrial dysfunction, which further rescued root tip cells from PCD, consequently activating defense strategies to protect plants from Cr toxicity and maintaining plant growth.

Oxidative stress and hepatocellular mitochondrial dysfunction attenuated by asiatic acid in streptozotocin-induced diabetic rats

Oxidative stress produced by mitochondria is one of the main causes for diabetes associated complications. This study was planned to assess the efficacy of asiatic acid (AA) on oxidative stress mediated hepatocellular mitochondrial dysfunction in streptozotocin (STZ)-induced type-2 diabetic rats. Diabetic rats were generated by intraperitoneal injection of STZ administered as single dose at 40 mg/kg body weight (b. wt.). Then the rats were treated with 20 mg of AA or 600 μg of glibenclamide (Glib)/kg b. wt, once in a day for 45 days. The results of this study illustrated that diabetic rat liver mitochondrial malondialdehyde (MDA), reactive oxygen species (ROS) and protein carbonyl (PCO) levels were significantly increased at the same time antioxidant enzymes and non-enzymes status was markedly diminished when compared with the liver mitochondria of normal control rats. A marked reduction in ROS, MDA, PCO and significant amelioration in non-enzymatic and enzymatic antioxidants were observed in diabetic rats treated with AA or Glib as compared with untreated diabetic control rats. Tricarboxylic acid (TCA) cycle enzymes like isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and electron transport chain (ETC) complexes activities were significantly diminished in diabetic rats. Besides, mitochondrial uncoupling protein-2 (UCP2) expression was significantly upregulated at the same time adenosine triphosphate (ATP) level and mitochondrial membrane potential (MMP) was markedly lowered in the mitochondria of diabetic rats. AA or Glib treatment with diabetic rats restored the TCA cycle enzymes activities, ETC complexes, UCP2, MMP and ATP level to near normal control rats as compared with untreated diabetic control rats. Hence, the results of the current study indicated that AA ameliorated mitochondrial function by attenuating oxidative stress in STZ-induced type-2 diabetic rats.

Sophoridine Regulates the NADPH Oxidase-2 Pathway and Potentiates the Cardioprotective Effect of Dexmedetomidine Against Sepsis-Induced Cardiomyopathy

We have evaluated the protective effect of sophoridine and dexmedetomidine alone and in combination against lipopolysaccharides induced myocardial dysfunction. Mitochondrial reactive oxygen species, malondialdehyde and superoxide dismutase in the myocardial tissue and inflammatory cytokines served as markers of oxidative stress and mitochondrial dysfunction. Data of the study suggest that myocardial function was improved with sophoridine alone and in combination with dexmedetomidine in septic mice. Also, there was reduction in the expression of NADPH oxidase 2, NADPH oxidase 4, p-Extracellular signal-regulated kinase/Extracellular signal-regulated kinase, p-P38/P38 and caspase-3 protein in the myocardial tissues of sophoridine-treated group than sepsis group of mice. In conclusion, data of the report reveals that sophoridine alone and in combination with dexmedetomidine shows synergistic effect against the management of sepsis induced myocardial injured mice by modulating the expression of NADPH oxidase 2.

Protective effect of gallic acid and gallic acid-loaded Eudragit-RS 100 nanoparticles on cisplatin-induced mitochondrial dysfunction and inflammation in rat kidney

Cisplatin is used as a chemotherapy drug in the treatment of various types of cancer. Mitochondrial dysfunction, oxidative stress and inflammation have been identified as major mechanisms of cisplatin nephrotoxicity. The present study investigated the protective effects of pure gallic acid and nanoparticle gallic acid nanoparticles (nano-gallic acid) on cisplatin induced nephrotoxicity. Nano-gallic acid was prepared by double emulsions-solvent evaporation technique using Eudragit RS 100 polymer and polyvinyl alcohol as carrier. Then, the physicochemical characterization of the nanoparticles was examined. In the present study, renal mitochondria were isolated using different centrifugal methods. Our data indicated that the doses of 50 and 100 mg/kg gallic acid and 10 mg/kg nano-gallic acid significantly decreased mitochondrial reactive oxygen species (ROS) formation, mitochondrial membrane damage (ΔΨm), mitochondrial malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and significantly increased mitochondrial glutathione (GSH), mitochondrial superoxide dismutase (MnSOD), mitochondrial glutathione peroxidase (GPX) and mitochondrial catalase compared to the cisplatin treated group. Histopathological studies also confirmed biochemical tests. Finally, our results confirmed that the pure gallic acid and its nanoparticle improved renal oxidative stress, inflammation and mitochondrial dysfunction in acute nephrotoxicity induced by cisplatin in rat. Nano-gallic acid (10 mg/kg) was selected as the most effective dose. The findings of this study showed the superiority of nano-gallic acid against pure gallic acid. In conclusion, nano-gallic acid-loaded Eudragit-RS 100 as a novel antioxidant can be considered in the treatment of renal complications of cisplatin.

KURKUMİN UYGULAMASININ YÜKSEK YAĞLI DİYETLE BESLENEN SIÇANLARIN TESTİS DOKUSUNDA OKSİDANANTİOKSİDAN SİSTEM ÜZERİNE ETKİSİ

Objective: High fat diet (HFD) induced oxidative stress is known to adversely affect testicular functions. Curcumin, which is an active ingredient of turmeric spice, has been shown to reduce lipid peroxidation and stimulate cellular antioxidant enzymes. The aim of this study is to investigate the effect of dietary curcumin on the testicular oxidant-antioxidant status in rats fed on a HFD. Material and Method: Male Sprague-Dawley rats were divided into four groups. Group 1 was fed with a control diet (10% of total calories from fat). Group 2 was fed with a HFD (60% of total calories from fat). Groups 3 and 4 received a HFD and a control diet with curcumin (1g/kg diet; w/w) respectively for 16 weeks. The testis tissue was homogenized and divided into postmitochondrial and mitochondrial fractions and the reactive oxygen species (ROS) levels were measured with the fluorometric method. The malondialdehyde (MDA) and glutathione (GSH) levels and glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione transferase (GST) activities were measured with spectrophotometric methods. Results: HFD supplementation increased postmitochondrial and mitochondrial MDA levels and decreased cytosolic GSH levels in testis. MDA levels decreased with curcumin supplementation. Moreover, GSH levels and GST activity increased.&nbsp;However, curcumin supplementation alone did not affect oxidant-antioxidant status. ROS levels, SOD and GPx activities did not change significantly between the groups. Conclusion: Our data has shown that curcumin supplementation with HFD may prevent testicular oxidant damage. However, further studies are needed to investigate the underlying molecular mechanisms.&nbsp;

Multi-walled carbon nanotubes induce oxidative stress, apoptosis, and dysfunction in isolated rat heart mitochondria: protective effect of naringin.

Multi-walled carbon nanotubes (MWCNTs) are material with exclusive features that can be applied in different fields including industrial and medicine. It has been determined that the accumulation of MWCNTs in the organs is along with genotoxic and cytotoxic injuries. Previous studies have shown mitochondrial dysfunction in MWCNTs exposure with cell lines, but their exact mechanisms with isolated mitochondria have remained unclear. The present study evaluated toxicity induced by MWCNTs in isolated rat heart mitochondria and protective effect of naringin. Our results showed that MWCNTs toxicity caused the prevention of heart mitochondrial complex II activity. Treatment of isolated heart mitochondria with MWCNTs led to an increase in mitochondrial reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) collapse, and mitochondrial malondialdehyde (MDA) and a decrease in mitochondrial glutathione (GSH) level and mitochondrial catalase (CAT) activity. Pretreatment of isolated heart mitochondria with naringin decreased mitochondrial oxidative damage through decreasing lipid peroxidation, returned mitochondrial complex II changes, decreasing MMP collapse and ROS production, and restoration of GSH level and CAT activity. Our findings indicated that MWCNTs had toxic effects on isolated heart mitochondria by inducing oxidative stress and possibly apoptosis pathway. The protection effects of naringin may be accompanied by mitochondrial conservation by its antioxidant property or due to its free radical scavenging. Our findings indicated that naringin had a possible role in preventing the mitochondria complaints in the heart.

Effects of Ca(NO3)2 Stress on Mitochondria and Nitrogen Metabolism in Roots of Cucumber Seedlings

Cucumber is a major vegetable crop grown in facilities, and its seedlings are sensitive to salinity. Thus, it is important for cucumber cultivation to research the effects of Ca(NO3)2. In this study, we investigated salt-sensitive Chunqiu (CQ) and salt-tolerant BoMei 49 (BM) seedlings, the changes to the enzymes involved in the mitochondria antioxidant system in the seedlings, and the changes in the MPTP (Mitochondrial Permeability Transition Pore) opening, mitochondrial membrane fluidity, mitochondrial membrane potential depolarization, mitochondrial electron transfer chain, and NO metabolism in response to Ca(NO3)2. Ca(NO3)2 stresses inhibited the growth of the cucumber seedlings, which showed a reduced root length, a decreased surface area and a decreased number of root tips, but a significantly increased root diameter. The mitochondrial malondialdehyde (MDA) content, H2O2 content, and O2− producing rate of the two cucumber roots were gradually increased in the Ca(NO3)2 treatment. The activity of superoxide dismutase (SOD) and peroxidation enzyme (POD) gradually increased, and catalase (CAT) activity gradually decreased. The electron transport chain activity of “BM” was higher than “CQ” under Ca(NO3)2 stress. Ca(NO3)2 stress destroyed the membrane structure of the mitochondria, so that the mitochondrial body tended to bend, causing double-membrane digestion and a hollow interior. Under the stress of Ca(NO3)2, the NO3− content of the seedlings increased significantly. The contents of NH4+ and NO, as well as the activities of nitrate reductase (NR), nitrite reductase (NIR), and nitric oxide synthase (NOS) decreased significantly. These findings provide physiological insights into root damage in response to salt stress for salt tolerance in cucumber.

Local and systemic effects of aging on acute pancreatitis

Background/Objectives: Evaluation of the local and systemic effects of aging on the severity of acute pancreatitis (AP) in an experimental rat model in elderly animals. MethodsAP was induced in Wistar rats by intraductal 2.5% taurocholate injection and divided into two groups: Young (3 month old) and Aged (18 month old). Two and 24 h after AP induction blood samples were collected for determinations of amylase, AST, ALT, urea, creatinine, glucose, and of plasma I-FABP. TNF-α and IL-6 levels were determined in serum and ascitic fluid. Liver mitochondrial function and malondialdehyde (MDA) contents, pancreas histological analysis, and pulmonar myeloperoxidade (MPO) activity were performed. Bacterial translocation was evaluated by bacterial cultures of pancreas. ResultsA significant increase in serum amylase, AST, ALT, urea, creatinine, glucose, I-FABP, and IL-6 levels, and a reduction in serum and ascitic fluid TNF-α levels were observed in the aged group compared to the young group. Liver mitochondrial dysfunction, MDA contents, and pulmonary MPO activity were increased in the Aged AP group compared to the Young AP group. Positive bacterial cultures obtained from pancreas tissue in aged group were significantly increased compared to the young group. Acinar necrosis was also increased in aged AP group when compared to young AP group. ConclusionAging worsens the course of acute pancreatitis evidenced by increased local and systemic lesions and increased bacterial translocation.

Fine particulate matter induces mitochondrial dysfunction and oxidative stress in human SH-SY5Y cells

Exposure to ambient fine particulate matter (PM2.5) is associated with neurodegenerative diseases. Mitochondrion is key to brain degeneration. However, the underlying mechanism of PM2.5-induced brain injury, especially mitochondrial damage, is still unclear. In this study, changes in mitochondrial dynamics, mitochondrial permeability transition pore (mPTP), mitochondrial DNA (mtDNA) and oxidative stress in human SH-SY5Y cells exposed to PM2.5 at different concentrations (0, 25, 100, and 250 μg mL−1) were investigated. The results showed that PM2.5 caused more mitochondrial swell, accompanied by the opening of mPTP and the decrease of ATP levels, mitochondrial membrane potential and mtDNA copy number in SH-SY5Y cells. PM2.5 significantly enhanced the expression of mitochondrial fission/fusion genes (Drp1 and OPA1) and affected the gene expression of CypD, SIRT3, and COX Ⅳ in SH-SY5Y cells. Besides, PM2.5 triggered the increase of cellular ROS, Ca2+ and Aβ-42 levels, inhibition of manganese-superoxide dismutase (SOD2) activities, reduction of GSH levels GSH/GSSG ratio, and elevation of mitochondrial malondialdehyde contents. It suggests that mitochondrial dysfunction and oxidative stress are the potential mechanisms underlying PM2.5-induced brain nerve cell injury, which may be related to neurological diseases. Additionally, our study elucidated that PM2.5 components trigger different cytotoxicity.

Effects of water extracts of Rehmannia glutinosa on antioxidant system of Nrf2 in paraquat-induced insulin resistance diabetic rat model.

The objective of this study was to observe the effects of water extracts of Rehmannia glutinosa on the antioxidant system of Nrf-2 in diabetic mice induced by paraquat, and to provide the basis for its further development. Thirty male mice were randomly divided into the control group, model group and observation group. The mice in the model group and the observation group were treated with paraquat to induce insulin resistance, with the control group injected with the same volume saline. After the model establishment, the mice in observation group was given 1.2 g/kg·day with water extract of Rehmannia glutinosa, and the other groups were given equal volume of 1% hydroxymethyl cellulose sodium. After 7 days, the glucose tolerance was detected and the body weight was measured before and after the treatment. The body weight of the mice in the model group was significantly decreased (P<0.05), but the body weight of mice in the observation group was significantly higher than that in the model group (P<0.05). After 7 days of model establishment, the glucose tolerance of mice was damaged, with the blood sugar increased, but the level of blood sugar was significantly decreased when treated with water extracts of Rehmannia glutinosa. The water extract of Rehmannia glutinosa increased the level of phosphorylation of PKB significantly compared to the model group with the inhibition of PTEN. The level of malondialdehyde in mitochondria and muscle tissue was significantly increased after treated with water extracts of Rehmannia glutinosa (P<0.05). With decreased NQO-1 protein expression and the nuclear translocation of Nrf-2 in the model group, the water extract of Rehmannia glutinosa cloud reverse the injury effectively. Similarly, the water extract of Rehmannia glutinosa significantly increased the expression of IКBα, which was significantly decreased in the model group. In conclusion, water extracts of Rehmannia glutinosa effectively reversed the glucose metabolism disorder in insulin resistance mice induced by paraquat, and effectively activated the level of Nrf-2 to enhance the muscle insulin signal while alleviating the insulin resistance in mice.

Potentiation of apoptosis in rat striatum exposed to endosulfan and the role of quercetin

This study focuses on evaluation of the toxic effect of enduslfan (END) and the quercetin (QUE) role in rat striatum. END (2 mg/kg) associated or not with QUE (10 mg/kg), was daily administered to animals during 6 days. Then, striatum mitochondria suspension was prepared by centrifugation to assess mitochondria swelling and redox status by determining malondialdehyde (MDA), glutathione-s-transferase (GST), catalase (CAT) and Glutathion (GSH). In addition, striatal lysate was also elaborated to determine apoptosis markers caspases-9 and 8; B-cell lymphoma2 (Bcl2) and Bcl2 associated X (Bax), by applying luminescence and ELISA methods. This study has shown an increase in mitochondria swelling and induction of apoptotic pathway. In addition, a decrease in mitochondrial enzymatic activity of GST and CAT was recorded as well as an increase in mitochondrial MDA rate and a fall in mitochondrial GSH level. By contract, QUE has maintained oxidative stress and apoptotic markers at their homeostasis levels and prevented striatum mitochondria swelling. Thus, endosulfan impairs redox status and membrane integrity of striatum mitochondria and induces apoptosis, but the use of QUE avoids these alterations.

Carnosic Acid Suppresses the H2O2-Induced Mitochondria-Related Bioenergetics Disturbances and Redox Impairment in SH-SY5Y Cells: Role for Nrf2

The phenolic diterpene carnosic acid (CA, C20H28O4) exerts antioxidant, anti-inflammatory, anti-apoptotic, and anti-cancer effects in mammalian cells. CA activates the nuclear factor erythroid 2-related factor 2 (Nrf2), among other signaling pathways, and restores cell viability in several in vitro and in vivo experimental models. We have previously reported that CA affords mitochondrial protection against various chemical challenges. However, it was not clear yet whether CA would prevent chemically induced impairment of the tricarboxylic acid cycle (TCA) function in mammalian cells. In the present work, we found that a pretreatment of human neuroblastoma SH-SY5Y cells with CA at 1μM for 12h prevented the hydrogen peroxide (H2O2)-induced impairment of the TCA enzymes (aconitase, α-ketoglutarate dehydrogenase (α-KGDH), succinate dehydrogenase (SDH)) and abolished the inhibition of the complexes I and V and restored the levels of ATP by a mechanism associated with Nrf2. CA also exhibited antioxidant abilities by enhancing the levels of reduced glutathione (GSH) and decreasing the content oxidative stress markers (cellular 8-oxo-2'-deoxyguanosine (8-oxo-dG), and mitochondrial malondialdehyde (MDA), protein carbonyl, and 3-nitrotyrosine). Silencing of Nrf2 by small interfering RNA (siRNA) abrogated the protective effects elicited by CA in mitochondria of SH-SY5Y cells. Therefore, CA prevented the H2O2-triggered mitochondrial impairment by an Nrf2-dependent mechanism. The specific role of Nrf2 in ameliorating the function of TCA enzymes function needs further research.

Energetic, oxidative and ionic exchange in rat brain and liver mitochondria at experimental audiogenic epilepsy (Krushinsky-Molodkina model).

The role of brain and liver mitochondria at epileptic seizure was studied on Krushinsky-Molodkina (KM) rats which respond to sound with an intensive epileptic seizure (audiogenic epilepsy). We didn't find significant changes in respiration rats of brain and liver mitochondria of KM and control rats; however the efficiency of АТР synthesis in the KM rat mitochondria was 10% lower. In rats with audiogenic epilepsy the concentration of oxidative stress marker malondialdehyde in mitochondria of the brain (but not liver) was 2-fold higher than that in the control rats. The rate of H2O2 generation in brain mitochondria of КМ rats was twofold higher than in the control animals when using NAD-dependent substrates. This difference was less pronounced in liver mitochondria. In KM rats, the activity of mitochondrial ATP-dependent potassium channel was lower than in liver mitochondria of control rats. The comparative study of the mitochondria ability to retain calcium ions revealed that in the case of using the complex I and complex II substrates, permeability transition pore is easier to trigger in brain and liver mitochondria of KM and КМs rats than in the control ones. The role of the changes in the energetic, oxidative, and ionic exchange in the mechanism of audiogenic epilepsy generation in rats and the possible correction of the epilepsy seizures are discussed.

3'-Daidzein sulfonate sodium improves mitochondrial functions after cerebral ischemia/reperfusion injury.

3'-Daidzein sulfonate sodium is a new synthetic water-soluble compound derived from daidzein (an active ingredient of the kudzu vine root). It has been shown to have a protective effect on cerebral ischemia/reperfusion injury in rats. We plan to study the mechanism of its protective effect. 3'-Daidzein sulfonate sodium was injected in rats after cerebral ischemia/reperfusion injury. Results showed that 3'-daidzein sulfonate sodium significantly reduced mitochondrial swelling, significantly elevated the mitochondrial membrane potential, increased mitochondrial superoxide dismutase and glutathione peroxidase activities, and decreased mitochondrial malondialdehyde levels. 3'-Daidzein sulfonate sodium improved the structural integrity of the blood-brain barrier and reduced blood-brain barrier permeability. These findings confirmed that 3'-daidzein sulfonate sodium has a protective effect on mitochondrial functions after cerebral ischemia/reperfusion injury, improves brain energy metabolism, and provides protection against blood-brain barrier damage.