Effects of cyclosporin on oxidative stress and mitochondrial energy metabolism in rat hippocampus after status epilepticus

AIM：To investigate the effects of cyclosporin on oxidative stress and mitochondrial energy metabolism in the rat hippocampus after status epilepticus. METHODS：Status epilepticus was induced by pilocarpine. The changes of malondialdehyde and superoxide dismutase in the rat hippocampus with or without cyclosporin injection were evaluated. Additionally, the mitochondrial permeability transition, the activity of mitochondrial respiratory chain complex I/III and ATP content in the rat hippocampus were detected. RESULTS：Cyclosporin significantly inhibited mitochondrial permeability transition in the rat hippocampus after status epilepticus. Decreased malondialdehyde and increased superoxide dismutase levels were detected in cyclosporin treatment group compared with status epilepticus group (P<0.05). More-over, the activity of mitochondria respiratory chain complex I, not III, in the mitochondrial fraction increased after cyclo-sporin treatment (P<0.05). In addition, cyclosporin significantly prevented the decrease of ATP content in rat hippocampus after status epilepticus (P<0.05). CONCLUSION：Cyclosporin suppresses oxidative stress in the rat hippocampus after status epilepticus. Cyclosporin alleviates the impairment of mitochondrial energy metabolism in rat hippocampus after status epilepticus.     

The characteristics of hypertrophic cardiomyocyte injury and the effect of intervention on energy metabolism after different time of hypoxia/reoxygenation

AIM:To investigate the characteristics of pathological injury and its relationship with the transformation of energy metabolism of hypertrophic cardiomyocytes after hypoxia-reoxygenation. METHODS:Cultured rat cardiomyocytes were induced to be hypertrophy by angiotensin Ⅱ (Ang Ⅱ) and norepinephrine (NE). Glucose oxidation rate (GOR), glucolysis rate (GLR) and fatty acid oxidation rate (FOR) were determined by liquid scintillation counting, and cell apoptosis was detected by TUNEL. RESULTS:(1) Compared with the normal cardiomyocytes (NC), the GOR and GLR were slightly higher and the FOR was slightly lower in the group of hypertrophic cardiac cells (HC) than that in the group of normal cardiomyocytes cultured under the normal oxygen partial pressure. The apoptosis rate had no difference between the two groups. (2) The apoptosis rate of hypertrophic cardiomyocytes after hypoxia was significantly higher than that of hypertrophic cardiomyocytes in normal culture. It was higher and moreover, some necrosis cardiomyocytes appeared after reoxygenation. (3) GOR and FOR in both group (NC and HC) were slightly lower in a time-dependent manner after hypoxia than that in each group in normal culture condition. GLR had no difference in both group. The GOR was more lower in both NC and HC group when reoxygenation than that at the point of hypoxia for 2 hours, but the GLR and FOR were significantly higher in HC than that in NC when reoxygenation. (4) The GOR was significantly higher and the GLR and FOR were significantly lower in the hypertrophic cardiomyocytes group (HC) with dichloroacetate (DCA, 1 000 μmol/L) or trimetazidine (TMZ, 1 μmol/L) treated respectively than that in the responded hypertrophic cardiomyocytes after stimulation by hypoxia-reoxygenation. In the meanwhile, the apoptosis rate also was markedly lower in the treated hypertrophic cardiomyocytes group. CONCLUSION:The transformation of energetic metabolism pathway plays an important role in the pathogenesis (mainly the apoptosis) of the hypertrophic cardiomyocytes after hypoxia-reoxygenation.     

Effects of acute and chronic hypoxia on rat brain mitochondrial translation activity

AIM: To investigate the effect of simulated high altitude hypoxia on rat brain mitochondrial translation activity. METHODS: Animals were continuously exposed to simulated 4 000 m high altitude in hypobaric chamber for three days and forty days. Mitochondria of rat brain were isolated by homogenizing brain tissue and following centrifuging program. Protein translation activity in isolated mitochondria in vitro was measured with [³H]-Lencine incorporation method. Products labeled with [³⁵S]-methionine in isolated mitochondrial protein synthesis system in vitro were separated on SDS-PAGE and identified by autoradiography. RESULTS: Mitochondrial translation activity in vitro in acute hypoxia exposure were significantly lower than control(P< 0.01). Mitochondrial translation activity in chronic hypoxia exposure were significantly higher than that in acute hypoxia exposure(P< 0.05), but showed no statistical difference between chronic and control. No differences in electrophoretic-autoradiography pattern of -methionine incorporation into translational products was observed among three groups. CONCLUSION: These results indicated that acute hypoxia exposure depressed synthesis of mitochondrial protein encoded by mitochondrial DNA in vitro and the changes in mitochondrial protein synthesis were related with hypoxia exposure time.     

Effects of repeated hypoxic exposures on saturation oxygen,mitochondrial function and ATP levels in the mouse brain

AIM: To study the effects of repeated hypoxic exposures on saturation oxygen and mitochondrial function in the brain. METHODS: A BALB/C mouse was placed in an air-sealed jar and hypoxic environment in the jar was established through consumption of the oxygen by respiration of the mouse. A gasp breath was regarded as the hypoxic tolerant limit of the mouse. The mouse was then transferred to a new jar. The mouse was exposed to hypoxia in this way for 5 times. In each run of hypoxic exposure, the hypoxic tolerance time, local brain saturation oxygen was measured. By the end of each hypoxic exposure, the mitochondrial complex I activity and ATP levels in the brain were also examined. RESULTS: The hypoxic tolerant time of a mouse increased during repeated hypoxic exposures. The saturation oxygen in the brain declined quickly during the first two hypoxic exposures, but recovered to the normal levels after a short fall during the third to fifth hypoxic exposures. The mitochondrial complex I activity decreased during repeated hypoxic exposures. The ATP levels declined by the end of the first hypoxic exposure, but increased by the end of the third and fifth hypoxic exposure. CONCLUSION: Repeated hypoxic exposures lead to increased oxygen saturation and ATP levels but decreased mitochondrial function. The increased ATP levels may be responsible for the increased hypoxic tolerance of the mouse brain.     

Effects of pioglitazone on myocardial energy metabolism and hemodynamics in rats with myocardial infarction

AIM: To observe the effects of pioglitazone on myocardial energy metabolism and hemodynamics in rats with heart failure after myocardial infarction (MI). METHODS: The model of MI was established by ligation of left anterior descending artery. The 20 surviving rats were randomly divided into MI group (n=10) and pioglitazone intervention group (P group,n=10, pioglitazone 3 mg·kg^-1·d^-1 orally). The sham-operated rats (SH, n=10) served as controls. Hemodynamic parameters were measured. The ratio of left ventricular weight to body weight (LVW/BW) and the ratio of right ventricular weight to body weight (RVW/BW) were calculated after 8-week treatment. The expression of PPARγ was examined by Western blotting. Mitochondrial respiratory function was determined by Clark oxygen electrodes. The size of adenine acid pool (ATP, ADP and AMP) in mitochondria was measured by HPLC. The adenine nucleotide translocator(ANT) activity was detected by the atractyloside-inhibitor stop technique. RESULTS: Compared with SH group, the protein expression of PPARγ was significantly decreased in MI group (P<0.01). The mitochondrial respiratory activity, the transport activity of ANT and the high-energy phosphate content were decreased in MI group (P<0.01), and the hemodynamic parameters were in disorder (P<0.01). Compared with MI group, the protein expression of PPARγ in P group was significantly increased. The mitochondrial respiratory activity, the high-energy phosphate content, the transport activity of ANT were improved (P<0.01). However, the hemodynamic parameters were not significantly changed.CONCLUSION: Pioglitazone increases the protein expression of PPARγ and improves myocardial energy metabolism in the development of heart failure in the rat model of myocardial infarction, but dose not change the hemodynamic parameters significantly.     

Effects of salvianolic acid B on the energy metabolism and hydrocephalus in mice with cerebral ischemia

AIM: To explore the effects of salvianolic acid B (SalB) on the energy metabolism and hydrocephalus in mice with cerebral ischemia.METHODS: NIH mice were randomly divided into four groups: sham-operated group,cerebral ischemia group,SalB-treated group and nimodipine-treated group.The brain tissue energy charge (EC),phosphocreatine (PCr),the activity of ATPase,excitability amino acid (EAA) content and water content of brain were measured when cerebral ischemia for 30 min.RESULTS: EC (0.520±0.034),PCr content ［(98.344±13.249) μmol/g］,the activity of Na⁺-K⁺-ATPase ［(0.593±0.013)×10³ U/g］ and Ca²⁺-ATPase ［(0.484±0.053)×10³ U/g］ in SalB-treated group were significantly higher than those in cerebral ischemia group {EC (0.465±0.037),PCr content ［(81.614±9.919) μmol/g］ ,the activity of Na⁺-K⁺-ATPase ［(0.244±0.065)×10³ U/g］,the activity of Ca²⁺-ATPase ［(0.321±0.086)×10³ U/g］} (P<0.01).The glutamate (Glu) content ［(0.405±0.110) μmol/g］,aspartate (Asp) content ［(0.141±0.020) μmol/g］ and water content of brain ［(38.1±0.1)%］ in SalB-treated group were markedly lower than those in cerebral ischemia group ［ Glu content (0.550±0.140) μmol/g,Asp content (0.287±0.050) μmol/g,water content of brain (44.1±0.1)%］ (P<0.05,P<0.01).CONCLUSION: The increase in cerebral energy metabolism and the activity of ATPase,and decrease in EAA content in brain tissue are the mechanism of SalB alleviating hydrocephalus at the early stage of cerebral ischemia in mice.     

Effect of mild hypothermia on energy metabolism and hydroxyl radical production after cerebral ischemia/reperfusion in gerbils

AIM: To study the effect of mild hypothermia on energy metabolism and hydroxyl radical production as well as delayed neuronal death (DND) in hippocampus during cerebral ischemia/reperfusion in gerbils.METHODS: Forebrain ischemia was induced by occluding bilateral common carotid arteries with aneurysm clamps for 10 min in gerbils. The DND in hippocampal CA1 sector was assessed by histological examination, and hydroxyl radical, ATP (adenosine triphosphate), ADP (adenosine diphosphate),AMP (adenosine monophosphate) levels were determined by high performance liquid chromatography with electrochemical or ultraviolet detection. RESULTS: The number of survival neuronal in hippocampal CA1 sector in mild hypothermia + I/R group was more than that in I/R group after ischemia/reperfusion 96 h. The content of 2,3-DHBA (2,3- dihydroxybenzoic acid) in hippocampus in I/R group was much higher than those in sham operation and mild hypothermia + I/R group after reperfusion 6 h (P＜0.01), but there were no significant differences in 2,3-DHBA outputs among 3 groups 48 h and 96 h after reperfusion. There were no obvious differences in ATP, ADP, AMP level in hippocampus among 3 groups 6 h after reperfusion. However, the content of ATP,ADP,AMP in mild hypothermia + I/R group was much higher than those in I/R group 48 and 96 h after reperfusion (P＜0.01).CONCLUSION: Mild hypothermia can reduced DND by improving the cerebral energy metabolism during forebrain ischemia/reperfusion in gerbils.     

Effect of cGMP on voltage-gated potassium channel in pulmonary artery smooth muscle cells from rats exposed to chronic hypoxia

AIM: To investigate the effect of cGMP on voltage-gated potassium channel in pulmonary artery smooth muscle cells (PASMCs) from rats exposed to chronic hypoxia. METHODS: (1) Wistar rats were randomly divided into control group (group A) and chronic hypoxia group (group B). Then group B received hypoxia 8 hours per day for 4 consecutive weeks. (2) Single PASMC was obtained via acute enzyme separation method. (3) Conventional whole-cell patch clamp technique was used to record resting membrane potential (Em) and ion currents of voltage-gated potassium channel. The changes of ion currents of voltage-gated potassium channel before and after applying cGMP (1 mmol/L), an agonist of protein kinase G (PKG), and cGMP plus H-8 (1 mmol/L), an inhibitor of PKG were compared between two groups. RESULTS: The Em of group B were significantly lower than that of group A. The ion currents of voltage-gated potassium channel in group A and group B were all significantly inhibited by cGMP [control group: from (118.0±5.0) pA/pF to (89.9±16.5) pA/pF, n=6, P＜0.05;chronic hypoxia group: from (81.0±5.0) pA/pF to (56.8±9.1) pA/pF, n=6, P＜0.05]and these effects were reversed by H-8 [control group: from (119.2±10.3) pA/pF to (117.8±9.1) pA/pF, n=6, P＞0.05;chronic hypoxia group: from (96.8±6.2)　pA/pF to (98.0±2.2)　pA/pF, n=6, P＞0.05]. CONCLUSIONS: The currents of voltage-gated potassium channel was inhibited by chronic hypoxic. The inhibitory effect of cGMP on currents of voltage-gated potassium channel in PASMCs from both normal and chronic hypoxic rats may be probably through the phosphorylation of voltage-gated potassium channel.     

Energy metabolism and apoptotic effect of microwave radiation on rat myocardial cells

AIM: To investigate the effect of microwave radiation at different intensities on the rat myocardium and its possible mechanism.METHODS: The rats were radiated by the intensity of 500, 1 000, 1 500 and 2 000 W/m² with 2 450 MHz microwave for 6 min. The heart tissue was collected 6 h after microwave radiation. ATP and mitochondria complex Ⅳ and Ⅴ were measured. The changes of the tissue structures were observed under transmission electron microscope. The apoptosis of the myocardial cells was detected by a cell analyzer. The protein level of cleaved caspase-3 was determined by Western blotting.RESULTS: The concentration of ATP and activity of mitochondria complex Ⅳand Ⅴ signi-ficantly decreased compared with control group in the cardiac tissues. The decreased number, morphological abnormalities such as dissolved cavitation, matrix and obvious tumefaction of mitochondria were observed under transmission electron microscope. The microwave radiation induced the apoptosis of myocardial cells in the rats. The cell apoptotic rate and the protein level of cleaved caspase-3 increased with increasing intensity of microwave radiation(P<0.05).CONCLUSION: Microwave radiation has obvious injury effect on the rat heart, which can cause cardiac energy metabolism dysregulation and cardiac myocyte apoptosis.     

Effect of mitochondrial aconitase activity on energy synthesis during aging

AIM：To investigate the effect of mitochondrial aconitase (ACO2) on energy synthesis during aging in male SD rats and D-galactose-induced cell aging model. METHODS：D-galactose at concentration of 55 mmol/L was used to establish MRC-5 cell aging model. Intact mitochondria in the rat brain and MRC-5 cells were isolated by a sucrose density gradient centrifugation. The formation of NADPH was used to represent the ACO2 activity and determined by observation of the absorbance at 340 nm. Fluorescence quantitative PCR and Western blotting were applied to detected ACO2 expression. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured by the commercial assay kits. The tissue iron content was detected by ferrozine method. Mitochondrial membrane potential was detected by JC-1 mitochondrial membrane potential detection kit. The content of ATP, ADP and AMP was measured by HPLC analysis, and the energy charge was then calculated by the formula. RESULTS：ACO2 activity and iron content presented age-related decline and increase, respectively, while the expression level of ACO2 kept stable. ACO2 activity significantly declined when the cells were treated with hydrogen peroxide at different concentrations. In the aging cells, SOD activity and ACO2 activity were decreased and MDA content was increased significantly, while the expression level of ACO2 was unchanged. During aging, mitochondrial membrane potential, ATP synthesis and energy charge presented significant reduction. CONCLUSION：The activity of ACO2, which is sensitive to oxidative stress, declines during aging, and may affect the efficiency of the Krebs cycle. At the same time, mitochondrial membrane potential decreases, thus reducing the energy synthesis in mitochondria.     

The effect of Shenmai injection on cardiac myocyte apoptosis after hypoxia

AIM: To observe the effect of Shenmai injection, a chinese medicine, on apoptosis of cardiac myocytes after hypoxia. METHODS: Cardiac myocytes were separated from neonate rat heart and cultivated in vitro. Hypoxia condition was induced by mixture of 95%N2 and 5%CO2. Cells were exposed to hypoxia for 6 h or 12 h and treated with Shenmai injection (5 mL/L) from 24 h before hypoxia until the end of hypoxia. First, apoptosis was detected with Annexin V-FITC and PI staining by flowcytometry. Then, the activity of cardiac myocyte mitochondria was observed by MTT method. Mitochondria membrane potential and the activity of caspase 3,7 were also measured by laser scan microscopy and multi-detection microplate reader, respectively. RESULTS: The apoptotic cells became more and more with prolonged hypoxia. Shenmai injection enhanced mitochondria activity, kept membrane potential, inhibited the activation of caspase3,7 and then decreased apoptotic cells (P<0.01). CONCLUSION: Hypoxia induces apoptosis in cardiac myocytes by mitochondria pathway. Shenmai injection can decrease cardiomyocyte apoptosis after hypoxia, the mechanism is related to mitochondria membrane potential stabilization and caspase inhibition.     

Oxidative stress damage to mitochondria mediated the pathological processes in epilepsy

Recent studies show that epileptic seizures result in mass free radical production and induce oxidative damage because of relative deficiency in anti-oxygen system. Mitochondrium is crucial to sustaining energy metabolism, regulating cell death, synthesising neurotransmitter and oxidating fatty acid. Mitochondrium is not only the place for free radical production, but also the target of oxidative damage. Mitochondrial oxidative stress and resultant dysfunction enhance epileptic susceptibility. Seizure-induced free radical can influence energy metabolism, destroy DNA construction and induce apoptosis in neurontoxic consequences in epilepsy.     

Effect of intestinal endotoxemia on hepatic energy metabolism in acute liver failure

AIM:To study the effect of intestinal endotoxemia(IETM) on hepatic energy metabolism in acute liver failure. METHODS:Intoxication by thioacetamide (TAA) was used to establish rat model of acute liver injury.Ketone body(acetoacetate and β-hydroxybutyrate) in arterial blood and ATP content of hepatocellular mitochondria were determined by using enzymatic fluorimetric micromethod.Colectomy was adopted in observing the changes in plasma endotoxin content and serum alanine aminotransferase (ALT) activity. RESULTS:In the TAA group,plasma endotoxin content and serum ALT activity were all significantly higher than those in the control group(P＜0.01),arterial ketone body ratio of acetoacetate to β-hydroxybutyrate (AKBR) decreased below 0.4,total ketone body in arterial blood was significantly lower than that in the control group(P＜0.01).In the TAA+colectomy group,there was no endotoxemia to be found,ATP content of hepatocellular mitochondria was significantly higher than that in the TAA group(P＜0.01), though serum ALT activity was higher than that in the control group(P＜0.05),but significantly lower than that in the TAA group(P＜0.01). CONCLUSION:IETM played a key role in the occurrence of acute liver failure,hepatic dysfunction might be caused by IETM through damaging hepatic energy metabolism.     

Effects of repeated hypoxia on the NPY-like immunoreactivity in the mouse brain

AIM:To observe the effects of repeated hypoxia on the neuropeptide Y(NPY)-like immunoreactivity in the mouse brain. METHODS:Forty male kunming mice were divided into 5 groups: Control, H₁(after the 1^sthypoxic run), H₂(the 2^nd hypoxic run), H₃(the 3^rdhypoxic run)and H₄(the 4^th hypoxic run). The hypoxic groups were subjected to different runs of hypoxia exposure. The NPY-like immunoreactivity in the moue brain was measured by using radioimmunoassary method.RESULTS: The standard tolerance time of the mouse exposed to hypoxia significantly increased following each increase in runs of hypoxia exposure. After the 1^st and 2^nd hypoxic run the NPY-like immunoreactivities in the mice brain significantly increased by 145.5%±3.2% and 147.3%±2.5% compared with the control(P＜0.01), respectively. However, the NPY-like immunoreactivites returned to the control levels after the 3^rd run. CONCLUSION:The repeated exposure to hypoxia can significantly enhance mouse's tolerance to hypoxia by preconditioning, and can induce the increase by only one exposure in NPY-like immunoreactivities of the mouse brain during the early period of formation of hypoxic preconditioning.     

Effects of levcromakalim on pulmonary arterial endothelial cells and smooth muscle cells exposed to hypoxia

AIM:To explore the effects of levcromakalim(Lev) on pulmonary arterial endothelial cells (PAEC) and smooth muscle cells (PASMC) exposed to hypoxia and the mechanisms involved.METHODS:The effects of Lev on [Ca²⁺]_i, and expression of PKC_α, eNOS, iNOS and PDGF-B mRNA and protein levels were observed. The nitrite (NO₂^-) and entothelin-1(ET-1) concentrations in supernatant in cultured PAEC and PASMC were measured. The proliferation and apoptosis of PASMC was also detected.RESULTS:When PASMC were exposed to hypoxia, Lev reduced concentration of ET-1 in cultured cell supernatant, lowed the expression of PKC_α, iNOS and PDGF-B both at mRNA and protein levels, decreased [Ca²⁺]_i concentration, increased proliferation and promoted the apoptosis in PASMC. However, in the presence of Lev, the [Ca²⁺]_i concentration was not changed in the hypoxic PAEC. The NO₂^- concentration in cultured cell supernant and expression of eNOS at mRNA and protein levels in hypoxic PASMC and PAEC were also unchanged. The downregulated ET-1 activity in PASMC and PAEC and proliferation in PASMC involved in the inhibition of PKC_α signaling pathway.CONCLUSIONS:Lev reduce some disadvatage effect of hypoxia on PASMC and PAEC. The mechanism of Lev action may partly involve in the downregulation of PKC_α signaling functions.     

Effect of L-arginine liposome on L-arginine transport of pulmonary artery in rats chronically exposed to hypoxia-hypercapnia

AIM: To investigate the effect of chronic hypoxia-hypercapnia and L-arginine (L-Arg) liposome on L-Arg transport in rats pulmonary artery. METHODS: Forty Sprague-Dawley rats were randomly divided into four groups, normal control group (NC), chronic hypoxia-hypercapnia group (HH), chronic hypoxia- hypercapnia group+L-Arg (HL) and chronic hypoxia-hypercapnia group+L-Arg liposome (HP). Changes in pulmonary artery L-Arg transport and pulmonary arterial microscopy were observed. RESULTS: (1) The mean pulmonary artery pressure (mPAP) and weight ratio of right ventricle to left ventricle and septum (RV/LV+S) in HH group were higher than those in NC group, and in HP group was lower than that in HH group and HL group, but there was no significant difference between HL group and HH group; (2) At 0.005 mmol/L, 0.01mmol/L, 0.02mmol/L, 0.05 mmol/L, 0.1 mmol/L and 0.2mmol/L concentration of L-Arg, the velocity of L-Arg transport in HH group was lower than that in NC group, and in HL group higher than in HH group, and in HP group was much higher than that in HH group and in HL group. (3) Light microscopy showed that vessel well area/total area (WA/TA) and media thickness of pulmonary arterioles (PAMT) were much higher in rats of HH group than those in NC group, WA/TA and PAMT in HP group were obviously improved. CONCLUSION: The above results indicated that there existed a functional disturbance in L-Arg transport of pulmonary artery in rats chronically exposed to hypoxia-hypercapnia, and it was obviously enhanced when liposome was used as L-Arg carrier. Thus, it appears that liposome-L-Arg may have clinical perspective in the treatment of chronic hypoxic pulmonary hypertension.     

Production of nitric oxide and change of nitric oxide synthase activity in brains mitochondria of the rats with focal cerebral ischemia/reperfusion

AIM and METHOD:To determine the production of nitric oxide(NO) and change of NO synthase(NOS) activity in mitochondria isolated from the rat brains of the ischemia/reperfusion rat model produced by transient occlusion of middle cerebral artery on the following time points:2 h after occlusion of artery and 30 min,2 h, 4h after reperfusion.RESULTS:After the occlusion of middle cerebral artery,the respiratory control rate(RCR) of mitochondria significantly decreased and slightly increased at 4h after reperfusion.Meantime,the production of NO in mitochondria increased significantly.But with the increase of perfusion, production of NO gradually decreased and reached normal level as in the control group.It also shows that cerebral ischemia increased NOS's activity significantly in the mitochondria and still kept a higher level than the control group although it decreased gradually after reperfusion.But the iNOS's activity did not show obvious change.The change of total NOS's activity depends on the change of cNOS's activity.CONCLUSION: The activation of NO/NOS system in the mitochondria might play an important role in the reperfusion injury during reperfusion of ischemic brain.     

Protective effect of astragalus polysaccharide on mitochondria and lysosome in H2O2-stressed skin fibroblasts

AIM: To verify the protection of astragalus polysaccharide (APS) on H2O2-stressed skin fibroblasts. METHODS: A model of acute H2O2 stress in primary skin fibroblast was used at concentration of 0.5 mmol/L by 30 min incubation. Dose responses of APS on cell survival was measured by MTT, cell death was evaluated by DAPI, and effect of APS on mitochondria, mitochondrial membrane potential and lysosome stabilization were measured by confocal microscopy. RESULTS: APS improved cell survival in a dose-dependent manner, starting at 0.5 mg/L and with a maximum at 1 mg/L. Moreover, APS inhibited mitochondrial membrane potential collapse, protected mitochondrial morphology and stablized lysosomal membrane. CONCLUSION: The results suggest the existence, at the mitochondria-lysosome level, of a new pathway of apoptotic regulation by APS. This might constitute a new therapeutic target where oxidative stress and lysosomal impairment are involved.     

Injury of hepatic mitochondria and its pathogenesis in rats with endotoxemia

AIM:To investigate the effect of endotoxin on rat hepatic mitochondria.METHODS:Rats were randomly divided into two groups:endotoxin group and the control. 8 cases of animals were included in each group. The effect of electron leak on the production of endogenous oxygen free radicals and the changes of mitochondria function were studied.RESULTS:Treated with endotoxin, a significant increase in O₂ and the rate of state 3,4 were observed in liver mitochondria; The rate of electron transfer to proton pump of mitochondria respiratory chain complex Ⅱ+Ⅲ(H⁺/2e^-), respiratory control rate and ADP/O decreased significantly.CONCLUSION:A increase in production of endogenous oxygen free radicals induced by endotoxin plays an important role in the injury of rat liver mitochondria.