抗氧化中药对慢性氟中毒大鼠肾脏SOD活性,MDA含量及超微结构的影响

为了进一步阐明氟中毒时肾脏损伤是否与脂质过氧化反应增强有关，特有含氟饮水给Ｗｉｓｔａｒ大鼠染氟，造成慢性氟中毒后，检查其肾脏超微结构变化，同时测定肾组织中ＳＯＤ活性及ＭＤＡ含量及超微并观察绞股兰皂甙－丹参复方中药氧化剂对肾脏损伤有地预防作用。取Ｗｉｓｔａｑｒ大鼠４０只，随机分３组；１且为正常对照组；２组为染氟对照组；３组为复方中药－染氟组。结果显示：与１组相比，２组动物尿氟、肾组织氟含量明显高于正     

SOD诱生剂对慢性氟中毒骨损伤的保护作用

用含氟饮水给ＳＤ大鼠染氟,同时服用ＳＯＤ诱生剂－－绞股蓝复方制剂,通过组织氟、尿氟、血清ＳＯＤ的测定以及骨组织的光镜观察及体视学分析,探讨氟中毒所致骨组织的损伤是否与脂质过氧化损伤有关,并观察绞股蓝复方制剂对氟中毒所致骨损伤有否保护作用。染氟４月后,示经处理的染氟大鼠血清ＳＯＤ显著降低,尿氟、骨氟明显升高;６月后,染氟对照大鼠出现骨髓腔狭窄,骨小梁面积浓度增大等骨质硬化表现,部分动物有骨赘形成。股     

绞股蓝总苷对老龄大鼠的抗氧化作用观察

目的：观察口服绞股蓝总苷对老龄大鼠的抗氧化作用。方法：测定药后大鼠红细胞超氧化物歧化酶（ＳＯＤ）和全血谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）等抗氧化酶含量及肾上腺内维生素Ｃ（ＶｉｔＣ）含量。结果：绞股蓝总苷４０和２０ｍｇ／ｋｇ连续用药２０ｄ能升高大鼠红细胞ＳＯＤ和全血ＧＳＨ－Ｐｘ酶活力,且能降低大鼠肾上腺皮质中ＶｉｔＣ含量。结论：绞股蓝总苷能增强老龄大鼠机体抗氧化能力及提高肾上腺皮质的功能。     

复方丹参注射液对银屑病患者血中红细胞指数和脂质过氧化?…

目的：通过对４５例银屑病患者应用复方丹参液治疗前后红细胞４项指数及血中ＭＤＡ、ＳＯＤ、ＧＳＨ－ＰＸ含量的研究，探讨复方丹参液对它们的影响及银屑病的发病机理。方法：测定银屑病患者用药前后血中红细胞的４项指数及ＭＤＡ、ＳＯＤ、ＨＳＨ－ＰＸ的含量，并与健康组比较。结果：银屑病患者红细胞４项指数均有异常，以平均红细胞体积（ＭＣＶ）和平均红细胞血红蛋白浓度（ＭＣＨＣ）改变最为显著（Ｐ〈０．０５），。血浆ＭＤ     

槲皮素对异丙肾上腺素所致大鼠心肌肥厚的影响

目的　研究槲皮素（ Ｑｕｅ） 对异丙肾上腺素（ Ｉｓｏ） 所致大鼠心肌肥厚的抑制作用及作用机制。方法　 Ｉｓｏ ００２ ｍｇ·ｋｇ－ １ ,每日两次,连续ｓｃ ６ ｗｋ ,形成大鼠心肌肥厚模型,分别测定心脏各重量参数、心肌过氧化脂质（ Ｌ Ｐ Ｏ） 含量、超氧化物歧化酶（ Ｓ Ｏ Ｄ） 活性及心肌 Ｃａ２ ＋ 和主动脉 Ｃａ２ ＋ 含量,培养乳鼠心肌细胞,应用 Ｆｕｒａ ２／ Ａ Ｍ 钙荧光指示剂技术测定心肌细胞内游离钙浓度。结果　 Ｉｓｏ 连续ｓｃ ６ ｗｋ 后,心肌和左心室重量明显增加,心肌 Ｌ Ｐ Ｏ 含量显著增加, Ｓ Ｏ Ｄ 活性下降,心肌 Ｃａ２ ＋ 和主动脉 Ｃａ２ ＋ 含量明显增加,给 Ｑｕｅ ７５ ｍｇ·ｋｇ－ １ ,１５０ ｍｇ·ｋｇ － １ 和维拉帕米１０ ｍｇ·ｋｇ － １ 后均能明显减轻心肌肥厚,降低 Ｌ Ｐ Ｏ 含量,增加 Ｓ Ｏ Ｄ 活性,降低心肌 Ｃａ２ ＋和主动脉 Ｃａ２ ＋ 的含量,应用 Ｆｕｒａ ２／ Ａ Ｍ 钙荧光指示剂技术发现 Ｉｓｏ 和 Ｈ２ Ｏ２ 能引起培养乳鼠心肌细胞内游离钙浓度明显升高。槲皮素对心肌细胞静息钙无明显影响,能抑制 Ｉｓｏ和 Ｈ２ Ｏ２ 致培养乳鼠心肌细胞内游离钙浓度的升高。结论　 Ｑｕｅ 能抑制 Ｉｓｏ 所引起的心肌肥厚, 该作用与清     

QK—全科广谱治疗仪对冠心病病人血液对氧化反应及红细胞变形？…

本实验测了３５例冠心病病人使用ＱＫ－全科广谱仪治疗前后血中红细胞超氧化物歧化酶（ＯＳＤ）活力;全血谷胱苷肽过氧化物酶（ＧＳＨ－Ｐｘ）,过氧化氢酶（ＣＡＴ）活力;血浆总抗氧化能力（ＡＯＡ）;红细胞膜丙二醛（ＭＤＡ）含量;红细胞滤过指数（ＩＦ）的变化。结果治疗全血ＧＳＨ－Ｐｘ、ＣＡＴ活力、血浆ＡＯＡ明显下降,红细胞膜ＭＤＡ含量明显升高,红细胞ＩＦ明显升高,后与治疗前比较,全血ＧＳＨ－Ｐｘ,ＣＡＴ活力及     

绞股蓝总皂苷对NCTC11637株HP延缓大鼠实验性胃溃疡愈合的治疗作用及其机制

目的探讨绞股蓝总皂苷（ｇｙｐｅｎｏｓｉｄｅｓ,ＧＰ）对ＣａｇＡ（＋）,ＶａｃＡ（＋）ＮＣＴＣ１１６３７株幽门螺杆菌（Ｈｅｌｉｃｏｂａｃｔｅｒｐｙ ｌｏｒｉ,ＨＰ）延缓动物实验性胃溃疡愈合的治疗作用及其机制。方法用醋酸诱发大鼠实验性胃溃疡,以溃疡面积、溃疡面积占腺胃部百分比、粘膜组织内白细胞介素 ８（ＩＬ ８）、ＰＧＥ２、ＭＤＡ、ＳＯＤ、·ＯＨ及溃疡愈合时间为指标,观察ｉｇ给予冻干ＮＣＴＣ１１６３７ＨＰ的影响及给予ＨＰ１ｈ后ｉｇＧＰ的治疗作用。结果单给ＨＰ组,溃疡面积加大,愈合延迟,粘膜组织内ＩＬ ８、ＭＤＡ升高,ＳＯＤ活性下降;·ＯＨ生成无明显变化;损伤粘膜组织内ＩＬ ８升高,ＰＧＥ２亦同时升高。ＨＰ＋ＧＰ组溃疡面积、溃疡面积百分率明显减小;粘膜内ＭＤＡ、·ＯＨ生成抑制,ＩＬ ８、ＰＧＥ２平行下降,ＳＯＤ活性提高。结论ＮＣＴＣ１１６３７株ＨＰ可明显延缓醋酸性大鼠胃溃疡的愈合;绞股蓝总皂苷通过抑制炎症反应过程中ＩＬ ８、ＭＤＡ、·ＯＨ生成,并通过提高ＰＧＥ２和ＳＯＤ活性增强胃粘膜保护机制,对感染ＮＣＴＣ１１６３７株ＨＰ大鼠实验性胃溃疡产生显著治疗作用。     

对妊高征患者红细胞膜脂质过氧化和离子运输功能的观察

目的：对妊高征患者红细胞膜过氧化脂质（ＬＰＯ）含量、超氧化物歧化酶（ＳＯＤ）活性、Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶活性及膜内面Ｃａ＾２＋结合能力的变化进行研究。方法：检测１９名正常妇孕,１９例妊高征患者红细胞膜ＬＰＯ、ＳＯＤ、Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶活性（比色法）及膜内面Ｃａ＾２＋结合力（原子吸收法）。结果：（１）妊高征组红细胞膜ＬＰＯ含量明显高于正常孕妇组（Ｐ〈０．００１）。（２）妊高征组红细胞膜Ｓ     

绞股蓝总皂苷对NCTC11637株HP延缓大鼠实验性胃溃疡愈合的治疗作用及其机制

目的探讨绞股蓝总皂苷（ｇｙｐｅｎｏｓｉｄｅｓ,ＧＰ）对ＣａｇＡ（＋）,ＶａｃＡ（＋）ＮＣＴＣ１１６３７株幽门螺杆菌（Ｈｅｌｉｃｏｂａｃｔｅｒｐｙｌｏｒｉ,ＨＰ）延缓动物实验性胃溃疡愈合的治疗作用及其机制。方法用醋酸诱发大鼠实验性胃溃疡,以溃疡面积、溃疡面积占腺胃部百分比、粘膜组织内白细胞介素８（ＩＬ８）、ＰＧＥ２、ＭＤＡ、ＳＯＤ、·ＯＨ及溃疡愈合时间为指标,观察ｉｇ给予冻干ＮＣＴＣ１１６３７ＨＰ的影响及给予ＨＰ１ｈ后ｉｇＧＰ的治疗作用。结果单给ＨＰ组,溃疡面积加大,愈合延迟,粘膜组织内ＩＬ８、ＭＤＡ升高,ＳＯＤ活性下降;·ＯＨ生成无明显变化;损伤粘膜组织内ＩＬ８升高,ＰＧＥ２亦同时升高。ＨＰ＋ＧＰ组溃疡面积、溃疡面积百分率明显减小;粘膜内ＭＤＡ、·ＯＨ生成抑制,ＩＬ８、ＰＧＥ２平行下降,ＳＯＤ活性提高。结论ＮＣＴＣ１１６３７株ＨＰ可明显延缓醋酸性大鼠胃溃疡的愈合;绞股蓝总皂苷通过抑制炎症反应过程中ＩＬ８、ＭＤＡ、·ＯＨ生成,并通过提高ＰＧＥ２和ＳＯＤ活性增强胃粘膜保护机制,对感染ＮＣＴＣ１１６３７株ＨＰ大鼠实验性胃溃疡产生显著治疗作用。     

蓣知子皂甙IV的结构

从木通科木通属植物白木通［Ａｋｅｂｉａｔｒｉｆｏｌｉａｔａ（Ｔｈｕｎｂ．）Ｋｏｉｄｚ．ｖａｒ．ａｕｓｔｒａｌｉｓ（Ｄｉｅｌｓ）Ｒｅｈｄ］种子的乙醇提取物中以硅胶层析等方法得四种三萜皂甙。其中甙ＩＶ是新天然产物，命名为蓣知子皂甙ＩＶ（ｙｕｚｈｉｚｉｏｓｉｄｅＩＶ）。根据化学和光谱分析，确定甙ＩＶ的结构为３－Ｏ－β－Ｄ－吡喃木糖基－（１→２）－ａ－Ｌ－吡喃阿拉伯糖齐墩果酸－２８－Ｏ－β－Ｄ－吡喃葡萄糖基－（１→６）－β－Ｄ－吡喃葡萄糖酯甙。另外皂甙Ｂ（Ｉ）、皂甙Ｃ（ＩＩ）和皂甙Ｄ（ＩＩＩ）为已知物。这些化合物在白木通种子中均是首次得到。     

Effect of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside on lipoprotein oxidation and proliferation of coronary arterial smooth cells

To investigate the effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG), a compound extracted from the root of Polygonum multiflorum Thunb, on lipoprotein (LDL and VLDL) oxidation, proliferation and nitric oxide (NO) content of coronary arterial smooth cells (CASMCs) induced by LDL, VLDL, ox-LDL and ox-VLDL. The oxidation level of lipoprotein was determined by thiobabituric acid (TBA) method and agarose gel electrophoresis. The proliferative degree was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) method. The NO content was assayed by nitrate reductase method. (1)THSG (0.1 - 100 mumol L(- 1)) could dose-dependently prevent lipoprotein from oxidation induced by Cu(2 + ) and CASMCs. (2)THSG (0.1 - 100 micromol L(- 1)) inhibited porcine CASMCs proliferation elicited by LDL, VLDL, ox-LDL and ox-VLDL. (3)THSG (0.1 - 100 micromol L(- 1)) counterpoised the decrease of NO content in CASMCs evoked by LDL, VLDL, ox-LDL and ox-VLDL. As compared with control, it was found that the threshold concentration of THSG, which significantly exerted the actions mentioned above, were at the concentration of 1 micromol.L(- 1) (P < 0.01). In conclusion, THSG possesses the antagonistic effects on oxidation of lipoprotein, proliferation and decrease of NO content of CASMCs, which partially explain the mechanism of anti-atherosclerosis of Polygonum multiflorum Thunb.     

Differential pulse voltammetric determination of the dopaminergic agonist bromocriptine at glassy carbon electrode

The electrochemical oxidation of bromocriptine at glassy carbon electrode has been carried out in Britton-Robinson (B-R) buffer solutions in the pH range 2.0-11.0 employing cyclic, linear sweep and differential pulse voltammetry (DPV). Bromocriptine showed one well-defined oxidation peak accompanied by a smaller one. The oxidation process was found irreversible. For analytical purposes, the well-resolved diffusion controlled voltammetric peak at pH 5 was critically investigated. The linear relationship between peak current height and bromocriptine concentration allowed the differential pulse voltammetric determination of the drug over a wide concentration range, from 0.04 to 5.00 microg ml(-1) with a detection limit of 0.01 microg ml(-1). A relative standard deviation of 1.44% at 0.1 microg ml(-1) level was obtained. The proposed DPV method was successfully applied for the individual tablet assay to verify the uniformity content of bromocriptine in commercial tablets.     

The structural and pharmacokinetic properties of oxidized human serum albumin, advanced oxidation protein products (AOPP)

To determine the pharmacokinetic properties of advanced oxidation protein products (AOPP), we prepared oxidized human serum albumin (oxi-HSA) using chloramine-T (a hypochlorite analogue) in vitro. The AOPP and dityrosine content of oxi-HSA (AOPP content, 244.3+/-12.3 microM; dityrosine content, 0.7+/-0.11 nmol of dityrosine/mg protein) were similar to those of uremic patients. In structural analysis, the increases in AOPP and dityrosine content of HSA induced slight decreases in its alpha-helical content. In pharmacokinetic analysis, oxi-HSA left the circulation rapidly, and organ distribution of oxi-HSA 30 min after intravenous injection was 51% for the liver, 23% for the spleen, and 9% for the kidney, suggesting that the liver and spleen were the main routes of plasma clearance of oxi-HSA. The liver and spleen uptake clearance of oxi-HSA were significantly greater than those of normal HSA (CLliver, 5058+/-341.6 vs 24+/-4.2 microL/hr [p<0.01]; CLspleen, 2118+/-322.1 vs 32+/-2.7 microL/hr [p<0.01]). However, uptake by other organs was not significantly affected by oxidation. These results suggest that the liver and spleen play important roles in elimination of AOPP.     

Antioxidant effect of atorvastatin is independent of PON1 gene T(-107)C, Q192R and L55M polymorphisms in hypercholesterolaemic patients

BACKGROUND: Serum paraoxonase (PON1), a high density lipoprotein (HDL)-bound antioxidant enzyme, plays a role in atherosclerosis. An increase in PON1 activity has been reported following statin treatment. OBJECTIVE: In the present study the following factors were evaluated: the influence of PON1 gene Q192R, L55M and T(-107)C polymorphisms on the response of LDL oxidisability and PON1 activity to atorvastatin treatment. RESEARCH DESIGN AND METHODS: 205 Sicilian subjects with primary hypercholesterolaemia (HCh) and 69 healthy subjects as controls were concurrently enrolled. Hypercholesterolaemic patients were randomly divided into two groups: an atorvastatin group (10 mg/day atorvastatin) and a placebo group. Lipid profile, markers of LDL resistance to in vitro oxidation (lag-phase, oxidation rate and thiobarbituric acid-reactive substances), vitamin E content in LDL, PON1 activity and genotypes in both HCh and control subjects were determined at baseline. The same parameters were measured again after 3 weeks of treatment in both the atorvastatin and placebo groups. RESULTS: HCh subjects showed significantly lower LDL resistance to oxidation, vitamin E content and PON1 activity levels than controls. A strong association was found among PON1 T(-107)C genotypes, LDL susceptibility to oxidation, vitamin E content and PON1 activity. After treatment, the atorvastatin group displayed a significant decrease in total cholesterol, LDL-cholesterol levels, and LDL susceptibility to oxidation, and an increase in vitamin E content and PON1 activity, compared with baseline values. Unlike PON1 activity levels, no difference among PON1 gene polymorphisms and reduction in markers of LDL oxidisability was observed. CONCLUSIONS: These results show, for the first time, that atorvastatin is able to improve the resistance to LDL oxidation independently of PON1 gene polymorphism.     

醋氯芬酸在多壁碳纳米管修饰电极上的电催化氧化及电分析方法

目的研究醋氯芬酸（aceclofenac,AC）在多壁碳纳米管修饰玻碳电极（MWCNTs/GCE）上的电化学氧化行为及电化学动力学性质,据此建立AC电化学定量测定方法。方法采用循环伏安法（CV）,计时电流法（CA）,方波伏安法（SWV）。结果 AC在GCE上于0.59 V处出现一氧化峰,与在GCE上相比,AC在MWCNTs/GCE上峰电位基本不变,峰电流增大约8倍。同时考察了实验条件对AC伏安行为影响,测定了电极反应过程动力学参数,并采用SWV研究了AC氧化峰电流与浓度之间的关系,表明氧化峰电流与其在2.0×10 6～2.0×10 4 mol.L 1内呈良好的线性关系,检出限（S/N=3）1.2×10 7mol.L 1。加样回收率在98.8%～105.0%之间,RSD在1.1%～2.8%之间。结论 AC电催化氧化是一受扩散控制的不可逆电极反应过程,MWCNTs/GCE对AC电化学氧化具有良好的催化作用,据此建立的电化学测定方法可用于市售AC药品含量的电化学定量测定。     

Modulation of islet ATP content by inhibition or stimulation of the Na(+)/K(+) pump

High (30 mM) K(+), known to cause beta-cell membrane depolarisation, significantly decreased the islet total ATP content, supporting the view that beta-cell membrane depolarisation can activate the ATP-consuming Na(+)/K(+) pump. Ouabain (1 mM) did not change the islet ATP content after 5-15 min of incubation in the absence or presence of 3 mM glucose but reduced it after 30 min, and in the presence of 20 mM glucose, the reduction by ouabain occurred already after 15 min. Incubation of islets with ouabain for 60 min decreased the islet ATP content in the presence of 3, 10 or 20 mM glucose or 30 mM K(+). Also, the islet glucose oxidation rate was decreased by ouabain. When K(+) deficiency was used to inhibit the Na(+)/K(+) pump, no change in ATP content was observed irrespective of glucose concentration, although K(+) deficiency caused a slight inhibition of the glucose oxidation rate. Diazoxide reduced the islet glucose oxidation rate and increased the islet ATP content in the presence of 20 mM glucose. There may exist a feedback mechanism decreasing the flow of glucose metabolism in response to reduced ATP consumption by the Na(+)/K(+) pump.     

Combined oestrogen-progestogen replacement therapy does not inhibit low-density lipoprotein oxidation in postmenopausal women

AIMS: The use of oestrogen containing hormone replacement therapy (HRT) is related to a significantly reduced atherosclerotic cardiovascular risk in postmenopausal women. Oestrogen is thought to be antioxidant and may inhibit low-density lipoprotein (LDL) oxidation in vitro. We investigated the effect of combined oestrogen and progestogen HRT on LDL oxidation in postmenopausal women. METHODS: Eighteen healthy women were given oestrogen/progestogen, and the susceptibility of LDL to oxidation was measured as the level of autoantibody to oxidative modified LDL and the production of conjugated dienes during copper-dependent oxidation after 3 and 6 months HRT. The levels of vitamin E, the major antioxidant in LDL, were also measured. RESULTS: After HRT, the anti-oxidatively modified LDL antibody level remained unchanged [1.58+/-0.16, 0.10 (-0.10, 0.26), and 0.08 (-0.09, 0.19), mean+/-s.d. at baseline, and mean change with 95% confidence intervals for differences at 3 and 6 months, respectively, P>0.05] as did the production of conjugated dienes when determined as lag phase [51.2+/-7.5, -0.3 (-3.9, 3.3), and 1.5 (-3.4, 6.4) min, P>0.05]. The LDL vitamin E content, measured as alpha-tocopherol, was also not altered [2.34+/-0.54, -0.07 (-0.27, 0.13), and -0.07 (-0.33, 0.16) nmol mg(-1) LDL, P>0.05] by treatment. CONCLUSIONS: Combined oestrogen and progestogen therapy for 6 months in postmenopausal women does not protect LDL against oxidation.     

Sodium Cefotaxime–Potato Starch Conjugate as a Potential System for Antibacterial Drug Delivery

Pharmaceutical Chemistry Journal - Sodium cefotaxime in a polymeric matrix of the periodate oxidation product of potato starch (68 mol% content of CHO groups) was synthesized. Formation of the...     

Effects of Antioxidants on the Hydrogen Peroxide-Mediated Oxidation of Methionine Residues in Granulocyte Colony-Stimulating Factor and Human Parathyroid Hormone Fragment 13-34

No HeadingPurpose. The effects and mechanisms of different antioxidants, methionine, glutathione, acetylcysteine, and ascorbic acid (AscH₂), on the oxidation of methionine residues in granulocyte colony-stimulating factor (G-CSF) and human parathyroid hormone fragment 13-34 (hPTH 13-34) by hydrogen peroxide (H₂O₂) were quantified and analyzed.Methods. The rates of oxidation of methionine residues in G-CSF were determined by peptide mapping analyses, and the oxidation of methionine residue in hPTH 13-34 was quantified by reverse-phase HPLC.Results. At pH 4.5, free methionine reduces, glutathione and acetylcysteine have no obvious effect on, and AscH₂ promotes the rates of oxidation of methionine residues in G-CSF. The H₂O₂-induced oxidation rate constants for free methionine, acetylcysteine, and glutathione at pH 4.5 were measured to be 32.07, 1.00, and 1.63 M^-1h^-1, respectively, while the oxidation rate constant for Met¹, the most readily oxidizable methionine residue in G-CSF, is 13.95 M^–1h^–1. Therefore, the different effects of free methionine, acetylcysteine, and glutathione on the rates of oxidation of methionine residues in G-CSF are consistent with their different reactivity toward oxidation by H₂O₂. By using hPTH 13-34, the effect of AscH₂ on the H₂O₂-induced oxidation of methionine residue was quantified, and the mechanisms involved were proposed. Because of the presence of trace transition metal ions in solution, at low concentrations, AscH₂ is prone to be a prooxidant, increasing the hydroxyl radical (OH) production rate via Fenton-type reactions. In addition to peroxide oxidation, these radicals lead to the degradation of hPTH 13-34 to smaller peptide fragments. At high concentrations, AscH₂ tends to act as an OH scavenger. EDTA inhibits OH production and thus eliminates the degradation of hPTH 13-34 by forming complexes with transition metal ions. However, the rate of oxidation of the methionine residue in hPTH 13-34 increases as the concentration of AscH₂ is increased from 0 to 200 mM, and the reason for this is still not clear.Conclusions. Our results demonstrate that free methionine is an effective antioxidant to protect G-CSF against methionine oxidation at pH 4.5. Acetylcysteine and glutathione are not effective antioxidants at pH 4.5. Their oxidation rates at different pH values imply that they would be much more effective antioxidants than free methionine at alkaline conditions. AscH₂ is a powerful electron donor. It acts as a prooxidant in the conditions in this study and is unlikely to prevent oxidation by H₂O₂ in protein formulation, whether or not EDTA is present.     

Activated peroxisomal fatty acid metabolism improves cardiac recovery in ischemia-reperfusion

Depressed oxidation of long chain fatty acids (LCFA) in heart ischemia leads to acute accumulation of LCFA metabolites that impair the functioning of the mitochondria. We hypothesized that reduced activity of carnitine palmitoyltransferase-I (CPT-I) might activate peroxisomal LCFA oxidation and protect mitochondrial function in ischemia and reperfusion. In the present study, despite the long-term threefold reduction in L-carnitine content by 3-(2,2,2-trimethylhydrazinium)-propionate, the uptake and oxidation rates of LCFA in the heart in normoxia were not significantly influenced. The significant increase in PPARα and PGC1α nuclear content, observed in this study, were followed by increased expression of genes involved in peroxisomal fatty acid oxidation (FAO) which compensated for the limited CPT-I-dependent FA transport into the mitochondria. In ischemia followed by reperfusion, the redirection of LCFA oxidation from mitochondria to peroxisomes protected the mitochondria from the accumulation of LCFA. In turn, the recovery of FAO resulted in significant reduction of myocardial infarct size. In conclusion, the decreased L-carnitine content in the heart preserves its peroxisomal and mitochondrial function after ischemia and improves cardiac recovery during reperfusion. The functional interplay between the decrease in L-carnitine and the PPARα/PGC1α pathway-induced redirection of FA metabolism protects the mitochondria against LCFA overload and provides a foundation for novel cardioprotective mechanisms.