Common Solvent Toxicity: Autoxidation of Respiratory Redox-Cyclers Enforced by Membrane Derangement

Abstract

Respiration, Lipophilicity, ProoxidantsUnspecific biological effects of chemically diverse solvents strikingly reveal the unifying motif of oxidant toxicity both in higher organisms and in aerobic bacteria. In a few spectacu lar cases, solvent metabolites with oxidant properties were dem onstrated, which however cannot explain extrahepatic toxicity, e.g. in muscle and nerve cells. A common source of solvent-inducible oxidants, by contrast, is suggested to be located in mitochondria or, more general, in m embranes where the respiratory chain operates. Orderly respiration depends on membrane integrity, which is invariably compromised by exposure to most solvents and many other lipophils. In rat mitochondria, toluene-induced membrane derangem ent has been di rectly implicated with superoxide production, resulting from autoxidation of the membranelocated respiratory redox-cycler ubisemiquinone. A related mechanism may occur in bacteria: Exposure of Escherichia coli to lipophils such as ethanol, tetralin, indole, chlorpromazine and procaine, or to heat shock, induces anti-oxidant proteins, which are reliable indicators of increased oxidant levels. Although many molecular details remain to be elucidated, this review documents that oxidant toxicity of lipophilic compounds is a common physiological phenom enon correlated with derangement of membranes where respiratory processes take place. Subjective consequences of acute oxidant injury are probably the hangover from alco hol and nicotine consumption, and the sudden death from recreational solvent abuse. Sugges tions concerning oxidants as major contributors to ageing remain unchallenged. T ren ds A r tic le -M in irev iew

The hyperfluidization of mammalian cell membranes acts as a signal to initiate the heat shock protein response

“…Finally, heat and other types of stress are associated not only with changes in the tension, fluidity, permeability or surface charges of membranes, and in lipid and protein rearrangements, but are also coupled with the formation of lipid peroxides and lipid adducts [40]. It may be noted that 4‐hydroxynonenal a highly reactive end‐product of lipid peroxidation, is an inducer of HSPs and has been suggested to play an important role in the initial phase of stress‐mediated signaling in K562 cells [41].…”

Toxic Damage to the Myocardium and Systemic Hemodynamic Disorders in Acute Propranolol Poisoning in the Experiment

“…Токсические концентрации препарата, гипоксия и возникающая декомпенсация кровообращения приводят к выраженной активации процессов свободнорадикаль ного окисления [21], что еще более усиливает деструкцию мембран и митохондриальную дисфункцию кардиомио цитов, приводя к разобщению окисления и фосфорили рования и, несомненно, влияет на состояние сердечно со судистой системы и миокарда в частности [22].…”

Inhibitor-associated transposition events in Corynebacterium glutamicum

“…Menadione is a superoxide generator, which was expected to result in the emergence of yeiH transposition mutants. As a lipophilic agent, however, menadione is likely to interfere with membrane integrity (Garbe and Yukawa 2001), which is also a possible indirect effect of fluoropyruvate toxicity, due to its interference with acetyl-CoA production (Bisswanger 1981), upon which fatty acid synthesis for membrane assembly relies. Altered fatty acid metabolism in fluoropyruvate-grown bacteria was often indicated by initial clumping of the bacteria, similar to the clumping of some of the related mycobacteria, which is known to rely solely on hydrophobic interaction.…”