Reactive Oxygen Species Over Production and Superoxide Dismutase Exhaustion Promoting the Intervertebral Disc Degeneration

Hiperglikemia pada Diabetes Melitus (DM) meningkatkan produksi Reactive Oxygen Species (ROS) dan berperan terhadap risiko komplikasi nefropati diabetik. Daun gedi merah (Abelmoschus manihot (L.) Medik) berkhasiat sebagai antidiabetik dan antioksidan tetapi penelitian ekstrak etanol daun gedi merah (EEDGM) untuk mencegah nefropati diabetik belum banyak dilaporkan. Penelitian ini bertujuan untuk mengetahui efek EEDGM terhadap kadar SOD dan MDA ginjal tikus model DM.Metode: Tikus Sprague dawley jantan usia 4-6 minggu dikelompokan menjadi 2 kelompok kontrol dan 3 kelompok perlakuan (n=25 ekor). Tikus DM dibuat dengan diet tinggi lemak-fruktosa (DTLF) dan streptozotocin (STZ) 25 mg/kgBB i.p multiple dose. Ekstrak etanol daun gedi merah (EEDGM) diberikan per oral selama 4 minggu. Kadar SOD dan MDA ginjal diukur menggunakan SOD rat kit dan MDA rat kit. Hasil dianalisa dengan One Way Anova dilanjutkan dengan uji BNT (p<0,05).Hasil: Pemberian EEDGM dosis 800 mg/kgBB menghambat penurunan kadar SOD jaringan ginjal dengan persentase sekitar 60% dibandingkan KDM (p<0,05). Pemberian EEDGM dosis 400 mg/kgBB menghambat peningkatan kadar MDA jaringan ginjal dengan persentase sekitar 20% dibandingkan KDM (p<0,05). Induksi DTLF dan STZ menurunkan kadar SOD jaringan ginjal dengan persentase sekitar 40% dan meningkatkan kadar MDA jaringan ginjal dengan persentase sekitar 30%.Kesimpulan: Pemberian EEDGM dapat menghambat penurunan kadar SOD dan peningkatan kadar MDA jaringan ginjal tikus model DM.

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Reactive Oxygen Species Mediate Low Back Pain by Upregulating Substance P in Intervertebral Disc Degeneration

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/6681815 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Jiancheng Zheng ◽

Jian Zhang ◽

Xingkai Zhang ◽

Zhiping Guo ◽

Wenjian Wu ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Low Back Pain ◽

Back Pain ◽

Substance P ◽

Intervertebral Disc ◽

Reactive Oxygen ◽

Alternative Methods ◽

Low Back ◽

Oxygen Species ◽

Ivd Degeneration

Reactive oxygen species (ROS) are thought to have a strong correlation with a number of intervertebral disc (IVD) diseases. Here, we aimed to determine whether ROS represent an etiology of low back pain (LBP) during IVD degeneration. Thirty degenerated intervertebral disc samples were obtained from patients, and ROS levels were quantified using dihydroethidium (DHE) staining. The results suggested a significant correlation between the ROS level and the severity of LBP. Subsequently, a puncture-induced LBP model was established in rats, and ROS levels significantly increased compared with those in the sham surgery group, accompanied with severe puncture-induced IVD degeneration. In addition, when ROS levels were increased by H2O2 administration or decreased by NAC treatment, the rats showed increased or decreased LBP, respectively. Based on this evidence, we further determined that stimulation with H2O2 in nucleus pulposus cells (NPCs) in vivo or in vitro resulted in upregulation of substance P (SP), a peptide thought to be involved in the synaptic transmission of pain, and that the severity of LBP decreased when SP levels were increased by exogenous SP administration or neutralized via aprepitant treatment in the IVDs of rats. In conclusion, ROS are primary inducers of LBP based on clinical and animal data, and the mechanism involves ROS stimulation of NPCs to secrete SP, which is a critical neurotransmitter peptide, to promote LBP in IVDs. Therefore, reducing the level of ROS with specific drugs and inhibiting SP may be alternative methods to treat LBP in the clinic.

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Detection of oxidative stress induced by calcium phosphate bions in human arterial endothelial cells

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/0031-2991.2021.01.70-78 ◽

2021 ◽

pp. 70-78

Author(s):

А.Г. Кутихин ◽

Д.К. Шишкова ◽

Р.А. Мухамадияров ◽

Е.А. Великанова

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Endothelial Cells ◽

Cell Death ◽

Superoxide Dismutase ◽

Calcium Phosphate ◽

Reactive Oxygen ◽

Oxygen Species ◽

Bafilomycin A1 ◽

Arterial Endothelial Cells

Введение. Кальций-фосфатные бионы (КФБ) формируются в организме человека при перенасыщении сыворотки ионами кальция и фосфора и вызывают дисфункцию эндотелия, однако молекулярные механизмы нарушения функционирования эндотелия при воздействии КФБ не ясны. Цель исследования - выяснение роли кальций-фосфатных бионов различной формы в развитии окислительного стресса в артериальных эндотелиальных клетках (ЭК) человека. Методика. Для детекции окислительного стресса к конфлюэнтным культурам первичных ЭК коронарной и внутренней грудной артерии человека добавляли равные концентрации КФБ сферической или игольчатой формы (СКФБ и ИКФБ соответственно) с последующим культивированием в течение 1 и 4 ч, добавлением флюоресцентных индикаторов окислительного стресса MitoSOX Red и CellROX Green и конфокальной микроскопией. Измеряли концентрацию продуктов перекисного окисления липидов в культуральной жидкости через 24 ч экспозиции эндотелиальных клеток КФБ. Анализ нейтрализации цитотоксических эффектов перекисного окисления липидов проводили путем добавления к ЭК супероксиддисмутазы и каталазы на 4 или 24 ч (одновременно с КФБ). Для сравнения механизмов клеточной гибели при воздействии СКФБ и ИКФБ анализировали цитотоксичность обоих типов бионов при одновременном воздействии лизосомального ингибитора бафиломицина А1. Результаты. Значимого увеличения генерации активных форм кислорода (АФК) в результате экспозиции СКФБ (независимо от линии ЭК и продолжительности экспозиции) не было выявлено. В то же время наблюдалось повышение генерации супероксида через 4 ч, а иных свободных радикалов через 1 ч после добавления ИКФБ к ЭК. Предварительная нейтрализация АФК супероксиддисмутазой и каталазой частично защищала ЭК от индуцируемой ИКФБ гибели. При этом добавление бафиломицина А1 к ЭК частично защищало их от гибели только при воздействии СКФБ, но не ИКФБ. Заключение. Гибель ЭК при воздействии СКФБ происходит в результате первичного повреждения лизосом, а при воздействии ИКФБ - в первую очередь вследствие окислительного стресса. Background. Calcium phosphate bions (CPB) form in the human blood upon its supersaturation with calcium and phosphate and provoke endothelial dysfunction; however, the molecular mechanisms of these pathological processes remain unclear. Aim. To elucidate the role of differently shaped CPBs in induction of oxidative stress in human arterial endothelial cells (Ecs). Methods. For detection of oxidative stress, equal concentrations of spherical CPB (CPB-S) or needle-shaped CPB (CPB-N) were added to confluent cultures of primary human coronary artery and internal thoracic artery ECs for 1 and 4 h; this was followed by MitoSOX Red and CellROX Green staining and subsequent confocal microscopy. Concentration of thiobarbituric acid-reactive substances was measured in the EC culture supernatant at 24 h of the CPB exposure. The lipid peroxidation cytotoxicity was neutralized by adding superoxide dismutase and catalase to ECs for 4 or 24 h. To compare cell death subroutines induced by CPB-S and CPB-N, the effect of bafilomycin A1, a lysosomal inhibitor, on CRB cytotoxicity was studied. Results. No increase in reactive oxygen species generation was observed in the CPB-S exposure, regardless of the EC line and exposure duration. However, addition of CPB-N to ECs increased the production of superoxide and other free radicals after four- and one-hour exposure, respectively. Prior neutralization of reactive oxygen species with superoxide dismutase and catalase partially protected ECs from CPB-N- but not CPB-S-induced death while bafilomycin A1, vice versa, protected ECs from CPB-S- but not CPB-N-induced death. Conclusion. CPB-S cause cell death due to primary damage of lysosomes whereas CPB-N induce apoptosis due to oxidative stress.

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Potentiation of Antibiofilm Activity of Amphotericin B by Superoxide Dismutase Inhibition

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/704654 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 12

Author(s):

Katrijn De Brucker ◽

Anna Bink ◽

Els Meert ◽

Bruno P. A. Cammue ◽

Karin Thevissen

Keyword(s):

Reactive Oxygen Species ◽

Superoxide Dismutase ◽

Candida Albicans ◽

Amphotericin B ◽

Reactive Oxygen ◽

Intracellular Reactive Oxygen Species ◽

Superoxide Dismutases ◽

Antibiofilm Activity ◽

Oxygen Species ◽

Ammonium Tetrathiomolybdate

This study demonstrates a role for superoxide dismutases (Sods) in governing tolerance ofCandida albicansbiofilms to amphotericin B (AmB). Coincubation ofC. albicansbiofilms with AmB and the Sod inhibitors N,N′-diethyldithiocarbamate (DDC) or ammonium tetrathiomolybdate (ATM) resulted in reduced viable biofilm cells and increased intracellular reactive oxygen species levels as compared to incubation of biofilm cells with AmB, DDC, or ATM alone. Hence, Sod inhibitors can be used to potentiate the activity of AmB againstC. albicansbiofilms.

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