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Effects of low-level light therapy on 2,3,7,8-tetrachlorodibenzo-p-dioxin and diabetes-induced oxidative damage in chicken and rat kidney.

机译:弱光疗法对2,3,7,8-四氯二苯并-p-二恶英和糖尿病引起的鸡和大鼠肾脏氧化损伤的影响。

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摘要

The objective of this study is to investigate the hypothesis that low-level light therapy (LLLT) with 670 nm light attenuates oxidative and bioenergetic stress and resulting renal damage induced by 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) and diabetes in chicken and rat kidney.;TCDD induces a wide range of adverse health effects in living organisms at least in part by inducing oxidative stress which provokes cellular injuries such as DNA and protein damage, lipid peroxidation, and cell death. TCDD-induced oxidative stress adversely affects developing kidneys and is implicated in progressive renal diseases and disorders such as necrosis in tubular cells, nephron hypertrophy and hyperplasia, and inflammatory nephritides. In addition, oxidative stress induced by diabetes contributes to the rate of progression and severity of diabetic complications, including diabetic nephropathy. The levels of reactive oxygen species (ROS) are under tight control by the protective actions of antioxidant defense systems in normal and healthy cells, but in diabetes and after TCDD exposure excessive cellular levels of ROS (oxidative stress) cause oxidative renal cell damage.;LLLT using light emitting diodes (LEDs) in the red to near infrared range has been employed in the treatment of soft tissue injuries and shown to promote tissue regeneration by increasing biological effects in cells. In the action spectra (630-1000 nm), the therapeutic effects of light treatment are mainly associated with the activation of cytochrome c oxidase, a primary photoacceptor molecule in the mitochondrial respiratory chain. The biological effects of LLLT vary according to wavelength, duration of light exposure, light intensity delivered, and energy density (dose or fluence). Among the wavelengths tested, the band in the range of 630-680 nm (peak at 670 nm) has been found to be optimal for light treatment by elevating the activity of cytochrome c oxidase.;The biochemical indicators of oxidative and energy stress in the chicken kidney exposed to TCDD (TCDD/LLLT study) were reversed by daily light therapy, restoring ATP and glutathione contents and increasing antioxidant enzyme activities to control levels. LLLT also normalized the level of lipid peroxidation increased by TCDD exposure. The results of this study demonstrated that LLLT could be useful as a non-invasive treatment for renal injury resulting from chemically induced cellular oxidative and energy stress. The study on the effects on a streptozotocin-induced rat model of chronic diabetes (Diabetes/LLLT study) was performed to clarify the hypothesis derived from the TCDD/LLLT study. The antioxidant effects of light treatment on diabetes-mediated kidney injury were also investigated biochemically to determine the potential of light treatment to negate the pathology caused by diabetes. Oxidative and energy stress were not induced in diabetic rats as clearly as in TCDD-exposed chickens, but daily phototherapy attenuated loss of renal function and antioxidant defense capabilities in diabetic animals, increasing the activity and expression of cytochrome c oxidase and catalase and the activity of Na K-ATPase. Levels of blood urea nitrogen reduced significantly in the diabetic rats were normalized to control levels by light therapy. LLLT also decreased the formation of DNA adduct (8-hydroxy-2'-deoxyguanosine, 8-OHdG).;Due to elevation of renal function and antioxidant defense systems by LLLT, LLLT is an appealing effective, non-invasive, and inexpensive therapy that could delay the development of progressive renal injury. The present study demonstrates that LLLT with 670nm light augments mitochondrial energy production and stimulates antioxidant protective pathways in injured renal cells. This non-invasive treatment may be of benefit in alleviating diabetes and other diseases that produce oxidative tissue damage and disrupt mitochondrial energy metabolism.
机译:这项研究的目的是研究假说,即采用670 nm光的低水平光疗(LLLT)可以减轻氧化和生物能应激以及2,3,7,8-四氯二苯并-对-二恶英(TCDD)引起的肾损害TCDD至少部分地通过诱导氧化应激引起活体生物体对健康的广泛不利影响,氧化应激可引起细胞损伤,例如DNA和蛋白质损伤,脂质过氧化和细胞死亡。 TCDD诱导的氧化应激会对发育中的肾脏产生不利影响,并与进行性肾脏疾病和疾病有关,例如肾小管细胞坏死,肾单位肥大和增生以及炎性nephritides。另外,由糖尿病引起的氧化应激有助于糖尿病并发症包括糖尿病性肾病的进展和严重程度。活性氧(ROS)的水平受到抗氧化剂防御系统在正常细胞和健康细胞中的保护作用的严格控制,但在糖尿病和TCDD暴露后,细胞中过高水平的ROS(氧化应激)会导致氧化性肾细胞损害。使用红色至近红外范围内的发光二极管(LED)的LLLT已被用于治疗软组织损伤,并显示出通过增加细胞中的生物效应来促进组织再生。在作用光谱(630-1000 nm)中,光治疗的治疗效果主要与细胞色素c氧化酶(线粒体呼吸链中的主要光受体分子)的激活有关。 LLLT的生物学效应根据波长,曝光持续时间,传递的光强度和能量密度(剂量或能量密度)而变化。在所测试的波长中,已发现630-680 nm(670 nm的峰值)范围内的光带是通过提高细胞色素C氧化酶的活性来进行光处理的最佳选择。每日光疗可逆转暴露于TCDD的鸡肾(TCDD / LLLT研究),恢复ATP和谷胱甘肽的含量,并增加抗氧化酶的活性以控制水平。 LLLT还使因TCDD暴露而增加的脂质过氧化水平正常化。这项研究的结果表明,LLLT可以作为化学诱导的细胞氧化和能量应激导致的肾损伤的无创治疗方法。进行了对链脲佐菌素诱发的慢性糖尿病大鼠模型的影响的研究(Diabetes / LLLT研究),以阐明源自TCDD / LLLT研究的假设。还对生化疗法研究了光疗对糖尿病介导的肾脏损伤的抗氧化作用,以确定光疗对消除糖尿病所致病理的潜力。并未像暴露于TCDD的鸡那样清楚地诱发糖尿病大鼠的氧化和能量应激,但是每天的光疗减弱了糖尿病动物肾功能和抗氧化防御能力的丧失,从而增加了细胞色素c氧化酶和过氧化氢酶的活性和表达以及Na K-ATPase。通过光疗法将糖尿病大鼠中血尿素氮水平显着降低至对照水平。 LLLT还减少了DNA加合物(8-hydroxy-2'-deoxyguanosine,8-OHdG)的形成。由于LLLT增强了肾功能和抗氧化防御系统,LLLT是一种有吸引力的有效,无创且廉价的疗法可能会延迟进行性肾损伤的发展。本研究表明,具有670nm光的LLLT可以增加线粒体能量的产生,并刺激受损肾脏细胞中的抗氧化保护途径。这种非侵入性治疗可能对减轻糖尿病和其他会引起氧化性组织损伤并破坏线粒体能量代谢的疾病有益。

著录项

  • 作者

    Lim, Jinhwan.;

  • 作者单位

    Indiana University.;

  • 授予单位 Indiana University.;
  • 学科 Health Sciences Toxicology.;Environmental Sciences.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 163 p.
  • 总页数 163
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 毒物学(毒理学);环境科学基础理论;
  • 关键词

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