Exendin-4体外通过抑制NF-κB-iNOS-NO信号减轻氧化应激诱导的小鼠MIN6胰岛β细胞凋亡

探讨胰高血糖素样肽-1受体激动剂Exendin-4(Ex-4)在氧化损伤诱导胰岛β细胞凋亡中的保护作用.培养的MIN6胰岛β细胞,通过AO-EB染色观察细胞凋亡形态,Annexin-V-PI染色流式技术测定凋亡率,Griess法检测细胞内一氧化氮水平,Western blotting检测胞浆iNOS蛋白、胞浆及胞核核因子-κBp65(NF-κBp65)蛋白表达水平.Ex-4可抑制叔丁基过氧化氢(t-BHP)诱导的β细胞凋亡,Ex-4(100nmol·L-1)预处理较单独t-BHP处理,其凋亡率减少约67%(P<0.001).Ex-4同时减少NO水平的增高,并抑制t-BHP诱导的β细胞NF-κBp65活化及iNOS蛋白表达水平.Ex-4可能通过抑制细胞内NF-κB活化、胞浆iNOS表达来抑制NO水平,最终减轻氧化损伤诱导的β细胞凋亡.     

苹果多酚对脂多糖刺激的RAW264.7细胞COX-2/PGE2和iNOS/NO表达的研究

目的 研究苹果多酚(APE)对脂多糖(LPS)诱发的RAW264.7细胞炎症COX-2/PGE2和iNOS/NO表达的抑制作用.方法 采用APE干预LPS刺激的小鼠单核/巨噬细胞RAW264.7,然后用Griess Reagent法和ELISA法检测细胞分泌的一氧化氮(NO)和前列腺素E2(PGE2)的水平,并且采用RT-qPCR和Western blotting技术检测APE对诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2)水平的影响以及核转录因子(NF-κB)的蛋白表达.结果 APE能显著抑制LPS刺激的RAW264.7细胞中NO、PGE2的含量,下调iNOS及COX-2的表达及NF-κB的磷酸化.结论 APE通过下调NF-κB的活性及iNOS与COX-2表达而发挥抗炎作用.     

葛根素对糖尿病大鼠视网膜的保护及对NF-κB表达的抑制

目的探讨糖尿病(DM)大鼠视网膜功能、超微结构的变化和NF-κB的表达及葛根素的干预作用。方法采用单次ip给予链脲佐菌素(STZ)60 mg·kg-1制备DM模型。ig给予葛根素125,250和500mg·kg-1组,连续给药4周。视网膜电图(ERG)测定视网膜功能、透射电镜观察视网膜超微结构、TUNEL法检测视网膜细胞凋亡以及免疫组织化学染色法检测视网膜组织NF-κB p65活性。结果与正常对照组相比,DM模型组ERG的b波振幅明显降低。与DM模型组相比,葛根素250和500 mg·kg-1组的b波振幅明显上升(P<0.05);透射电镜下见DM模型组视网膜神经节细胞,内、外核层细胞均出现线粒体改变。葛根素干预后超微结构改变明显好转。与正常对照组相比,DM模型组视网膜细胞凋亡指数显著增高以及NF-κB p65表达明显增强,葛根素干预后各组凋亡指数均显著下降,葛根素250和500 mg·kg-1组NF-κB p65表达显著下降(P<0.05)。结论 DM大鼠早期即出现神经视网膜功能和超微结构的改变,葛根素可抑制NF-κB的活化,抑制视网膜神经细胞的凋亡从而起到保护神经视网膜的作用。     

依替巴肽对急性心肌梗死模型大鼠心肌一氧化氮、过氧化物及核转录因子的影响

目的:研究依替巴肽对急性心肌梗死模型大鼠心肌一氧化氮(NO)、过氧化物及核转录因子的影响。方法:将大鼠随机分为假手术组、模型组和依替巴肽低、中、高剂量(30、60、90μg/kg)组,除假手术组外其余各组大鼠建立无复流急性心肌梗死模型,于再灌注前30 min股静脉注射相应药物。检测各组大鼠心肌NO、总一氧化氮合酶(tNOS)、内皮型一氧化氮合酶(eNOS)、诱导型一氧化氮合酶(iNOS)、髓过氧化物酶(MPO)、丙二醛(MDA)水平和核转录因子-κB p65(NF-κB p65)的阳性表达。结果:与假手术组比较,模型组和依替巴肽低、中、高剂量组大鼠的NO、tNOS、iNOS、MPO、MDA水平与NF-κB p65表达均明显升高(P<0.05),eNOS活性降低(P<0.05)。与模型组比较,依替巴肽低、中、高剂量组大鼠的NO、iNOS、MPO、MDA水平与NF-κB p65表达均明显降低(P<0.05),依替巴肽中、高剂量组大鼠的tNOS水平明显降低(P<0.05)、eNOS水平明显升高(P<0.05),且与剂量呈正相关。结论:依替巴肽可通过保护血管内皮、减少中性粒细胞浸润及氧自由基释放、抑制NF-κB p65激活,从而减少急性心肌梗死模型大鼠的无复流现象。     

热休克蛋白70激动剂SW02对脂多糖诱导的巨噬细胞iNOS表达的调控及机制

目的观察热休克蛋白70(Hsp70)激动剂SW02对脂多糖(LPS)诱导的RAW264.7细胞诱导型一氧化氮合酶(iNOS)表达及一氧化氮(NO)生成的作用,并探讨其作用机制。方法采用LPS诱导RAW264.7细胞建立细胞炎症模型,将细胞随机分为DMSO组、DMSO+LPS(1 mg·L~(-1))组、SW02组和SW02+LPS(1 mg·L(-1))组。Western blot法测定蛋白表达;Griess试剂法测定NO含量;实时定量PCR法测定iNOS mRNA表达;染色质免疫共沉淀法(ChIP)检测核因子κB(NF-κB)与iNOS启动子结合能力变化。结果 SW02明显抑制由LPS诱导的RAW264.7细胞iNOS蛋白、mRNA表达和NO释放(SW02+LPS组iNOS表达量和NO生成量明显低于DMSO+LPS组,P<0.01或P<0.05);SW02不影响由LPS诱导的RAW264.7细胞κB-α抑制子(IκB-α)降解(SW02+LPS组IκB-α表达量与DMSO+LPS组比差异无显著性,P>0.05)和NF-κB入核(SW02+LPS组细胞质、细胞核NF-κB表达量与DMSO+LPS组比差异无显著性,P>0.05);SW02明显抑制由LPS诱导的NF-κB与iNOS启动子结合(SW02+LPS组NF-κB与iNOS启动子结合量明显低于DMSO+LPS组,P<0.05)。结论 SW02抑制巨噬细胞iNOS表达和NO生成,其机制可能与抑制NF-κB与iNOS启动子结合有关。     

N-乙酰半胱氨酸对心衰兔氧化应激和核因子NF-κB的干预研究

目的探讨N-乙酰半胱氨酸对心衰兔氧化应激和核因子NF-κB的干预研究。方法 40只健康成年大白兔,耳缘注射阿霉素制作心衰模型。8周后取造模成功的27只大白兔随机分为心衰组(n=14)和N-乙酰半胱氨酸组(NAC组,n=13),另取10只为对照组。对照组和心衰组给予注射生理盐水1 m L/(kg·d),NAC组给予注射NAC 300 mg/(kg·d)。干预4周后,测定各组兔超声心动图参数(LVEDD、LVESD、IVST、EF、FS)、血清及心肌组织总抗氧化能力;酶联免疫检测各组兔血清和心肌组织8-iso-PGF2α的含量;免疫组化和Western blot检测NF-κB p65及其抑制物IκB-α在左室心肌细胞的表达和核结合活性的改变。结果与对照组相比,心衰组兔左室舒张期末内径(LVEDD)、左室收缩期末内径(LVESD)明显增大(P<0.05);射血分数(EF)与短轴缩短率(FS)明显降低(P<0.05),室间隔厚度(IVST)未见明显变薄。心衰组血清和心肌的总抗氧化能力均低于对照组(P<0.01);与心衰组比较,NAC干预组总抗氧化能力明显升高(P<0.05),与对照组比较差异无统计学意义。NAC注射组较心衰组心肌细胞NF-κB p65向核内移位表达的阳性细胞明显减少,NAC治疗后兔心肌细胞NF-κB p65的表达较心衰组减少(P<0.05),IκB-α表达较心衰组多(P<0.05)。心衰后给予NAC干预的兔血清和心肌组织8-iso-PGF2α含量较心衰组显著降低(P<0.05),血清和心肌8-iso-PGF2α的含量均与心功能显著相关(r=0.975,P<0.005;r=0.974,P<0.05)。结论氧化应激参与了心力衰竭的发生和心功能的恶化;NAC可通过抑制氧化应激,拮抗NF-κB的活化和其在核内的表达,减少心肌细胞凋亡及炎症反应,有效改善心功能,保护心肌。     

银杏叶提取物对大鼠实验性结肠炎肿瘤坏死因子-α表达的影响

目的观察银杏叶提取物对三硝基苯磺酸灌肠诱导大鼠实验性结肠炎肿瘤坏死因子-α(TNF-α)的影响及其作用机制。方法大鼠随机分为正常对照组、三硝基苯磺酸模型组、阳性药物对照组、EGB组4组。用三硝基苯磺酸灌肠诱导大鼠实验性结肠炎,评估结肠组织大体形态和组织学评分;生化法检测大鼠肠组织谷胱苷肽过氧化物酶(GSH-Px)活性及一氧化氮(NO)含量;免疫组化检测肠组织TNF-α,核因子-κBp65(NF-κBp65)蛋白表达。逆转录聚合酶链反应(RT-PCR)检测肠组织诱生型一氧化氮合酶(iNOS)表达。结果EGB组大体形态和组织学评分较模型组明显下降,GSH-Px活性明显增高,NO含量明显减少,结肠黏膜TNF-α,NF-KBp65和iNOS表达明显降低。结论EGB可能通过抑制TNF-α的表达和NF-κBp65及iNOS的激活从而抑制炎症级联来保护TNBS诱导的实验性结肠炎。     

知母皂苷通过调节NF-κB-iNOS-NO信号通路抑制LPS诱导的RAW264.7细胞功能

目的研究知母皂苷(SAaB)对脂多糖(LPS)诱导的RAW264.7细胞功能的影响,以及对NF-κB-诱导型一氧化氮合酶(iNOS)-NO信号通路的调节。方法以LPS刺激RAW264.7细胞构建体外炎症细胞模型,采用Griess法和ELISA法分别检测SAaB干预下,RAW264.7炎症细胞中的NO、iNOS、肿瘤坏死因子α(TNF-α)和白介素-6(IL-6)的含量;Western blot检测RAW264.7细胞NF-κB p65蛋白的表达水平。结果 RAW264.7细胞在LPS(10 mg·L~(-1))诱导下,NO、iNOS、TNF-α、IL-6的含量以及NF-κB p65蛋白表达水平与正常对照组比较均明显增高。SAaB(0.3、3、30 mg·L~(-1))可明显降低RAW264.7炎症细胞中NO、iNOS、TNF-α和IL-6的含量(P<0.01),且明显下调NF-κB p65的蛋白表达水平(P<0.01)。结论 SAaB可通过调节NF-κB-iNOS-NO信号通路,抑制LPS诱导的RAW264.7细胞功能。     

糖尿病心肌组织中NOS的改变与糖尿病心肌病关系探讨

目的探讨实验性糖尿病(DM)大鼠模型心肌组织中一氧化氮(NO)浓度和一氧化氮合酶(NOS)活性改变在DM心肌病发生和发展中的作用.方法SD大鼠一次注射链脲佐菌素(STZ)建立DM模型,成模后36只DM大鼠分批每两周检测空腹血糖和NO浓度,2、6、10周时进行心肌组织NOS活性检测.结果(1)DM大鼠血清中NO的浓度与对照组相比显著升高(P＜0.01),并随着血糖浓度的升高及时间的延长而升高.(2)DM组大鼠心肌组织NO浓度和NOS的活性均较对照组明显升高(P＜0.05).结论高血糖状态激活了心肌组织中的NOS,使心肌组织中NO过度增加,加上血液中过度升高的NO,损伤了心肌细胞的结构及其功能,可能是DM心肌病产生的重要机制之一.     

Diclofenac enhances proinflammatory cytokine-induced nitric oxide production through NF-κB signaling in cultured astrocytes

Recently, the number of reports of encephalitis/encephalopathy associated with influenza virus has increased. In addition, the use of a non-steroidal anti-inflammatory drug, diclofenac sodium (DCF), is associated with a significant increase in the mortality rate of influenza-associated encephalopathy. Activated astrocytes are a source of nitric oxide (NO), which is largely produced by inducible NO synthase (iNOS) in response to proinflammatory cytokines. Therefore, we investigated whether DCF enhances nitric oxide production in astrocytes stimulated with proinflammatory cytokines. We stimulated cultured rat astrocytes with three cytokines, interleukin-1β, tumor necrosis factor-α and interferon-γ, and then treated the astrocytes with DCF or acetaminophen (N-acetyl-p-aminophenol: APAP). iNOS and NO production in astrocyte cultures were induced by proinflammatory cytokines. The addition of DCF augmented NO production, but the addition of APAP did not. NF-κB inhibitors SN50 and MG132 inhibited iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. Similarly, NF-κB p65 Stealth small interfering RNA suppressed iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. LDH activity and DAPI staining showed that DCF induces cell damage in cytokine-stimulated astrocytes. An iNOS inhibitor, l-NMMA, inhibited the cytokine- and DCF-induced cell damage. In conclusion, this study demonstrates that iNOS and NO are induced in astrocyte cultures by proinflammatory cytokines. Addition of DCF further augments NO production. This effect is mediated via NF-κB signaling and leads to cell damage. The enhancement of DCF on NO production may explain the significant increase in the mortality rate of influenza-associated encephalopathy in patients treated with DCF.     

嗜酸乳杆菌调节NO及其氧化介质对动脉粥样硬化模型大鼠的影响

目的 研究嗜酸乳杆菌对一氧化氮（NO）及其氧化介质表达的影响,探讨嗜酸乳杆菌抗动脉粥样硬化的机 制。方法 24只SPF级雄性大鼠随机分为正常饮食组、高脂饮食组和嗜酸乳杆菌组,每组8只。正常饮食组大鼠以 普通饲料喂养,高脂饮食组以高脂饲料+腹腔注射维生素D3+免疫损伤法+FeSO4喂养建立动脉粥样硬化模型,嗜酸 乳杆菌组大鼠在高脂饮食组的基础上,每天灌胃0.5 mL嗜酸乳杆菌菌液（1×109 CFU/mL）,实验第4、8、12周末称量动 物体质量。喂养 12 周后处死动物,检测血清氧化低密度脂蛋白（oxLDL）、NO、精氨酸、精氨酸酶、过氧亚硝基 （ONOO-）含量。分离大鼠主动脉血管,HE染色观察主动脉形态学变化,Real-time PCR检测eNOS、iNOS mRNA表达, Western blot 检测主动脉NF-κB p65亚基的表达。结果 （1）整个实验过程中,高脂饮食组和嗜酸乳杆菌组大鼠体质 量变化差异无统计学意义（P＞0.05）,但较正常饮食组均有明显增长（P < 0.01）。（2）HE染色结果显示,高脂饮食大鼠 中主动脉形成广泛的动脉粥样硬化病变,嗜酸乳杆菌组大鼠的主动脉形态得到明显改善,仅内皮细胞增生,没有观 察到平滑肌细胞的坏死。（3）与正常饮食组相比,高脂饮食组大鼠血清oxLDL、ONOO-、精氨酸酶、主动脉iNOS mRNA 和细胞核NF-κB p65表达水平升高（P＜0.01）,血清NO和精氨酸含量、主动脉eNOS mRNA 及胞质NF-κB p65亚基表 达水平降低（P＜0.01）;而嗜酸乳杆菌恰好能逆转上述改变（P＜0.01）。结论 嗜酸乳杆菌可能通过调节NOS的表 达、增加NO生物利用度、保护内皮功能来发挥抗动脉粥样硬化作用。     

Fulvic acid promotes extracellular anti-cancer mediators from RAW 264.7 cells,causing to cancer cell death in vitro

Fulvic acid (FA) is known to promote electrochemical balance as a donor or a receptor possessing many biomedical functions. Nevertheless, the effect of FA on the anti-cancer activity has not been elucidated. In the current study, we first isolated FA from humus and investigated whether FA regulates immune-stimulating functions, such as production of nitric oxide (NO), in RAW 264.7 cells. Our data showed that FA slightly enhances cell viability in a dose-dependent manner and secretion of NO from RAW 264.7 cells. It upregulated the protein and mRNA expression of inducible NO synthesis (iNOS). In addition, FA enhanced the DNA-binding activity of nuclear factor-κB (NF-κB) in RAW 264.7 cells; the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC) effectively attenuated the expression of FA-stimulated iNOS, suggesting that FA stimulates NF-κB to promote iNOS and NO production. Finally, FA-stimulated culture media (FA-CM) from RAW 264.7 cells were collected and MCA-102 fibrosarcoma cells were cultured in this media. The FA-CM augmented MCA-102 fibrosarcoma cell apoptosis; however, an NO inhibitor N^G-monomethyl-l-arginine (NMMA) slightly inhibited the FA-CM-mediated MCA-102 fibrosarcoma cell apoptosis, which was accompanied by low levels of NO. In the present study, we found that FA induces the generation of NO and iNOS in RAW 264.7 cells by inducing NF-κB activation; however, NO did not significantly stimulate MCA-102 fibrosarcoma cell apoptosis in the current study. In addition, FA-CM enhanced cell death in various human cancer cells such as Hep3B, LNCaP, and HL60. Taken together, FA most likely stimulates immune-modulating molecules such as NO and induces cancer cell apoptosis.     

Melatonin attenuates gentamicin-induced nephrotoxicity and oxidative stress in rats

The present study investigated the protective effects of melatonin (MT) against gentamicin (GM)-induced nephrotoxicity and oxidative stress in rats. We also investigated the effects of MT on induction of apoptotic cell death and its potential mechanisms in renal tissues in response to GM treatment. The following four experimental groups were evaluated: (1) vehicle control, (2) MT (15?mg/kg/day), (3) GM (100?mg/kg/day), and (4) GM&MT. GM caused severe nephrotoxicity as evidenced by increased serum blood urea nitrogen and creatinine levels, increased renal tubular cell apoptosis, and increased Bcl2-associated X protein and cleaved caspase-3 protein expression. Additionally, GM treatment caused an increase in levels of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) protein expression in renal tissues. The significant decreases in glutathione content, catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase activities and the increase in malondialdehyde content indicated that GM-induced tissue injury was mediated through oxidative reactions. In contrast, MT treatment protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by the GM treatment. Histopathological studies confirmed the renoprotective effect of MT. These results indicate that MT prevents nephrotoxicity induced by GM in rats, presumably because it is a potent antioxidant, restores antioxidant enzyme activity, and blocks NF-κB and iNOS activation in rat kidney.     

Salvianic acid A inhibits induction of inflammatory mediators by blocking Nuclear Factor-κB activation in macrophages

Objective To investigate the anti-inflammation effect and possible mechanism of Salvianic acid A(SAA)in mouse peritoneal macrophages.Methods Peritoneal macrophages were obtained from BALB/c mice.LPS induced nitric oxide(NO),tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in supernatant,protein expression of inducible nitric oxide synthase(iNOS),matrix metalloproteinase-9(MMP-9)and activation of nuclear factor-kappa B(NF-κB)in the extract were measured.Results SAA strongly inhibited the excessive production of NO,TNF-α and IL-6 in LPS-induced peritoneal macrophages in a concentration-dependent manner and blocked the expression of iNOS and MMP-9.Treatment with LPS alone increased the translocation of NF-κB(p65)from cytosol to the nucleus,but the SAA inhibited the translocation of NF-κB(p65).Conclusions The results showed that SAA had strong anti-inflammatory effects in LPS-stimulated peritoneal macrophages.The important mechanism is due to its inhibition of NF-κB activation.     

The effect of ethanol and N-nitrosodimethylamine on the iNOS-dependent NO production in human neutrophils. Role of NF-κB

1.?The objective of study was to determine the influence of ethanol and/or N-nitrosodimethyloamine (NDMA) on the inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production by human neutrophils and determination of the role of NF-κB in this process.

2.?Isolated polymorphonuclear leukocytes (PMNs) derived from 15 human volunteers were incubated in the presence of ethanol and/or NDMA. Expression of the tested proteins were evaluated using the Western blot method. Total NO metabolites was assayed in the cell cultures by Griess reaction.

3.?In neutrophils exposed to ethanol or NDMA was observed an increased NF-κB-dependent NO production mediated by iNOS with the contribution of MAP kinases: p38 and JNK. An inhibiting effect of NF-κB signaling pathway on the MAP kinases was observed, which are involved in the iNOS-dependent NO production. By the simultaneous effect, ethanol and NDMA caused stronger generation of NO by neutrophils without the contribution of iNOS. Inhibition of NF-κB in cells simultaneously exposed to the xenobiotics caused a decreased expression of MAP kinases.

4.?Individual and simultaneous effect of ethanol and NDMA may cause disorders in the response of immune system. However, the joint effect of the tested substances results in uncontrolled interactions, leading to cascading disorders of signal transduction.     

Lectin purified from Musca domestica pupa up-regulates NO and iNOS production via TLR4/NF-κB signaling pathway in macrophages

The present study reported that nitric oxide (NO) was up-regulated by the induction of lectin purified from Musca domestica pupa (MPL) in macrophages without cytotoxicity. The mRNA expression and protein secretion of inducible nitric oxide synthase (iNOS) were strongly induced by MPL treatments. Subsequent investigation revealed that the nuclear factor-κB (NF-κB) inhibitory κB (IκB) in endochylema was inhibited and NF-κB translocated into the nucleus after MPL treatment. Meanwhile, the IKKβ was strongly induced and the production of the toll-like receptor 4 (TLR4) was significantly up-regulated. Moreover, MPL increased NO production via inducing the expression of iNOS through the activation of NF-κB, which suggested that MPL probably acted as an activating agent of the NF-κB activation.     

双环醇对脂多糖诱导巨噬细胞iNOS蛋白的表达和NF-κB活化的抑制作用

目的炎症是肝炎病毒或其它因素所致的肝损伤的一个共同特征,该文目的系研究抗肝炎新药双环醇对与炎症反应相关分子的调节作用。方法以无毒性浓度双环醇预先与巨噬细胞株RAW264.7和小鼠腹腔巨噬细胞温孵1h后,加入一定量脂多糖(LPS)共同培养适当时间以诱导上述细胞的活化,培养上清中NO2-的含量和TNF-α的水平分别用Griess试剂及L929细胞株生物法测定,用Westernblot方法测定iNOS蛋白的表达和NF-κB的活化。结果双环醇在0.1～0.5mmol.L-1剂量依赖性降低1mg.L-1LPS引起的RAW264.7和小鼠腹腔巨噬细胞NO的释放以及TNF-α的分泌,双环醇0.5mmol.L-1能够明显抑制1mg.L-1LPS引起的iNOS蛋白的表达和NF-κB的活化。结论双环醇对与炎症相关的调控因子iNOS蛋白的表达和NF-     

Differential modulation of immunostimulant-triggered NO production by endoplasmic reticulum stress inducers in vascular smooth muscle cells

We investigated the effects of endoplasmic reticulum (ER) stress inducers thapsigargin (TG) and tunicamycin (Tm) on immunostimulant lipopolysaccharide/interferon (LPS/IFN)-induced expression of isoform of nitric oxide synthase (iNOS) and nitric oxide (NO) production in vascular smooth muscle cells. LPS/IFN-induced iNOS mRNA expression was markedly enhanced by TG, whereas iNOS mRNA expression was strongly attenuated by Tm. Similarly, production of iNOS protein was markedly upregulated by TG but virtually eliminated by Tm. LPS/IFN-induced guanosine triphosphate cyclohydrolase I mRNA expression was slightly reduced by TG and markedly inhibited by Tm. Similarly, LPS/IFN-mediated induction of cellular biopterin was modestly reduced by TG and markedly inhibited by Tm. TG modestly enhanced LPS/IFN-induced activation of NF-κB, whereas Tm had no effect on it. Cellular respiration was reduced by TG and Tm in a concentration-dependent manner, which was confirmed by apoptosis assay. Thus, TG and Tm-induced ER stress and differently modulated NO production through alterations in iNOS expression and activity independently of NF-κB activation and caused a similar degree of ER stress-induced apoptosis.