A rigorously simple quantitative model for free radical behavior in aerobic biological systems.

IF 2.8 4区医学 Q2 DERMATOLOGY Skin Pharmacology and Physiology Pub Date : 2024-11-16 DOI:10.1159/000542600

Leonhard Zastrow, Jürgen Lademann, Martina C Meinke, Silke B Lohan

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引用次数: 0

Abstract

Background Human life is based on oxygen respiration and an enzymatic, free radical-dependent water chemistry, whose billions of parallel reactions take place at pH ∼7.4 and a temperature of 37°C, in accordance with the laws of chemistry. The cellular metabolic processes occur over time periods covered by the half-lives of ROS (reactive oxygen species) for °OH to over 10 s for LOS (lipid oxygen species), indicating that mixtures of free radicals form the basic components for these processes. Summary and Key Messages The main source of radicals is the mitochondrial conversion of 1-5 % oxygen into "primary" ROS and "secondary" LOS. Every endogenous and exogenous radical generation, triggered by "natural background radiation", "natural environment" or "solar radiation" leads to qualitatively similar mixtures of "primary" ROS and "secondary" LOS or RNS (reactive nitrogen species). A Multilevel Antioxidant Regulation, Repair and Protection System (MARRPS) keeps these radical mixtures in a steady state. Depending on the total number of free radicals, different areas of radical action are defined. The Free Radical Ground State (FRGS) with "homeostasis" and "adaptive homeostasis", the Free Radical Threshold Value (FRTV) and Free Radical Pathological Conditions (FRPC). The quantitative ratio ROS > LOS comprehensively characterizes the "homeostasis" and "adaptive homeostasis" area of the FRGS. The total number of free radicals cannot be measured directly in the "homeostasis" area. "Adaptive homeostasis" is achieved when excess radicals are stable produced beyond "homeostasis" of the FRGS. The quantity that remains controllable in this range is a maximum of ∼3.58 10¹² radicals/mg, the value of the body constant FRTV. The sensitized MARRPS provides "semi-stable homeostatic" states characterized by dual stability with ROS > LOS and a stable total ROS/LOS and RNS count beyond the basal FRGS "homeostasis". If the total number of all radicals exceeds the FRTV, where LOS > ROS, this initiates uncontrolled radical chain reactions. The partial failure of the MARRPS in the FRPC area leads to pathological processes which are the starting point for a hundred different diseases. The design principle described by this simple model applies universally to all aerobic life.

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有氧生物系统中自由基行为的严格简单定量模型。

背景人类生命的基础是氧呼吸和依赖于酶的自由基水化学，其数十亿个平行反应在 pH ∼ 7.4 和 37°C 的温度下按照化学规律进行。细胞新陈代谢过程发生的时间跨度从 ROS（活性氧）的半衰期（°OH）到 LOS（脂氧）的 10 秒以上，这表明自由基混合物构成了这些过程的基本成分。总结和重要信息自由基的主要来源是线粒体将 1-5%的氧气转化为 "一级 "ROS 和 "二级 "LOS。由 "天然本底辐射"、"自然环境 "或 "太阳辐射 "引发的每一种内源性和外源性自由基的产生，都会导致 "初级 "ROS 和 "次级 "LOS 或 RNS（活性氮物种）质量相似的混合物。多级抗氧化调节、修复和保护系统（MARRPS）可使这些自由基混合物保持稳定状态。根据自由基总量的不同，自由基的作用区域也不同。自由基原态（FRGS）包括 "稳态 "和 "适应稳态"、自由基阈值（FRTV）和自由基病理状态（FRPC）。ROS > LOS 的定量比值全面描述了 FRGS 的 "稳态 "和 "适应性稳态 "区域。在 "稳态 "区域无法直接测量自由基的总数。当过量自由基的稳定产生超出 FRGS 的 "稳态 "范围时，就实现了 "适应性稳态"。在此范围内，可控制的自由基数量最大为 3.58 10¹²个/毫克，即人体常数 FRTV 的值。敏化的 MARRPS 可提供 "半稳定平衡 "状态，其特点是 ROS > LOS 双重稳定，ROS/LOS 和 RNS 总量稳定，超出了 FRGS 基础 "平衡 "状态。如果所有自由基的总数超过 FRTV，即 LOS > ROS，就会引发失控的自由基连锁反应。在 FRPC 区域，MARRPS 的部分失效会导致病理过程，而这正是百种不同疾病的起点。这个简单模型所描述的设计原理普遍适用于所有有氧生命。

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来源期刊

Skin Pharmacology and Physiology 医学-皮肤病学

CiteScore

5.20

自引率

7.40%

发文量

审稿时长

>12 weeks

期刊介绍： In the past decade research into skin pharmacology has rapidly developed with new and promising drugs and therapeutic concepts being introduced regularly. Recently, the use of nanoparticles for drug delivery in dermatology and cosmetology has become a topic of intensive research, yielding remarkable and in part surprising results. Another topic of current research is the use of tissue tolerable plasma in wound treatment. Stimulating not only wound healing processes but also the penetration of topically applied substances into the skin, this novel technique is expected to deliver very interesting results.

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