Endogenous Detoxification

One of the most important functions of GSTs is the detoxification of endogenous as well as exogenous substances via conjugation with glutathione... 

Methaemoglobin forming compounds should be used cautiously in victims suffering from concurrent carbon monoxide poisoning or hypoxia. The second approach calls for provision of additional sulfur groups to enhance the detoxification of cyanide and thiocyanate by endogenous rhodanese this comes about by giving sodium thiosulphate. 

All tissues except mature red blood cells are able to manufacture haem for use in the respiratory cytochrome proteins of the electron transport chain. However, the liver is an especially important site of haem synthesis because it (a) is a major organ of erythropoiesis in utero and (b) haem-containing cytochrome-P450 (CYP-450) enzymes play significant roles in hepatic detoxification of drugs, toxins and endogenous waste products (Section 6.4). 

In conclusion, it is clear that a variety of stereoelectronic (internal) factors and external conditions favor a substantial positive charge in the transition state of diol epoxides as they undergo hydration or react with nucleophiles [115-118], Interpreting the reactivity of diol epoxides (or of numerous other electrophilic metabolites) in terms of toxification vs. detoxification is particularly difficult since toxicity depends as much on the nature of the endogenous nucleophile as on the intrinsic reactivity of the metabolites. 

Uric acid is the end product of the purine metabolism. When uric acid excretion via the kidneys is disturbed, gout can develop (see p. 190). Creatinine is derived from the muscle metabolism, where it arises spontaneously and irreversibly by cyclization of creatine and creatine phosphate (see p. 336). Since the amount of creatinine an individual excretes per day is constant (it is directly proportional to muscle mass), creatinine as an endogenous substance can be used to measure the glomerular filtration rate. The amount of amino acids excreted in free form is strongly dependent on the diet and on the ef ciency of liver function. Amino acid derivatives are also found in the urine (e.g., hippu-rate, a detoxification product of benzoic acid). 

There is now a wide consensus that HA is a product of normal metabolism, and that its toxicity, and that of substituted HAs, is manifested only at concentrations well above those expected when HA is produced as a result of normal cell metabolism. However, despite the fact that N-hydroxylation is a key detoxification reaction for various drugs, the lack of convincing direct in vivo measurements of HA itself in healthy individuals does not permit a definitive conclusion as to its normal endogenous levels as a harmless species in mammalian cells. 

Despite the scarcity of direct evidence, HA is generally believed to be present as a metabolic intermediate in mammalian tissues Recent studies on the reductive detoxification of HAs both by human NADH-cytochrome i>5 reductase and by human cytochrome b5 may be considered as additional supporting evidence for the in vivo formation of HA in mammalian cells that needs to be controlled in order to avoid the toxic effects of an excess of endogenously produced HA, as well as of HA produced by detoxification of xenobiotic HA derivatives " . 

Bagchi and Kleiner suggested that endogenous HA can undergo dismutation by the action of a cyanobacterial hydroxylamine dismutase, thereby providing a detoxification mechanism for excess hydrogen peroxide, as well as for an excess of HA itself. This... 

Because alcohol and barbiturates also act, in part, via the GABA receptor-mediated chloride ion channel, benzodiazepines show cross-tolerance with these substances. Thus, benzodiazepines are used frequently for treating alcohol or barbiturate withdrawal and detoxification. Alcohol and barbiturates are more dangerous than benzodiazepines because they can act directly at the chloride ion channel at higher doses. In contrast, benzodiazepines have no direct effect on the ion channel the effects of benzodiazepines are limited by the amount of endogenous GABA. 

In order to remove the endogenous toxicosis, we have applied various methods of detoxification in 22 patients. In 14 cases, one or two sessions of plasmapheresis were performed. Biochemical markers used for determining the level of toxemia were middle molecules . In six cases, against the background of intensive care, oral sorption (enterosorption) was administered 2-3 days after operative intervention. 

We snggest that the extracorporeal elimination of proteases from blood and decrease in the level of toxic and biologically active peptides stimnlate endogenous detoxification systems and improve functioning of the compensatory systems in the organism. 

The reason for this increase in mortality is considered to be due to the displacement of other fat-soluble antioxidant such as y-tocopherol (29) and to the possible inhibition of the cytosolic glutathione S-transpherase, which is involved in the detoxification process of endogenous toxins (30). One of the oxidized metabolites of vitamin E, the vitamin E quinone, has a very strong activity as an inhibitor of vitamin Independent clotting mechanism (3 I),... 

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