Glutathione
(GSH) and Detoxification
Cysteine
metabolism and metal toxicity
Quig D. [Altern Med Rev 1998 Aug;3(4):262-70] The pro-oxidative
effects of metals are compounded by the fact that the metals also
inhibit antioxidative enzymes and deplete intracellular glutathione.
Cysteine has a pivotal role in inducible, endogenous detoxication
mechanisms in the body, and metal exposure taxes cysteine status.
Basic research pertaining to the transport of toxic metals into the
brain is summarized, and a case is made for the use of hydrolyzed
whey protein to support metal detoxification and neurological function.
Early detection and treatment of metal burden is important for successful
detoxification, and optimization of nutritional status is paramount
to the prevention and treatment of metal toxicity.
Mechanism
of action and value of N- acetylcysteine in the treatment of early
and late acetaminophen poisoning: A critical review.
Jones AL. [Journal of Toxicology -- Clinical Toxicology. 1998;
volume 36, number 4, pages 277-285] The mechanism of action of N-acetylcysteine
in early acetaminophen poisoning is well understood, but much remains
to be learned of the mechanism of its possible benefit in acetaminophen
poisoning presenting beyond 15 hours. Candidate mechanisms for a beneficial
effect in-clude improvement of liver blood flow, glutathione replenishment,
modification of cytokine production, and free radical or oxygen scavenging.
Glutathione
deficiency in alcoholics: risk factor for paracetamol hepatotoxicity.
Lauterburg BH and Velez ME. [Gut. 1998; volume 29, pages 1153-1157].
"The data indicate that low glutathione may be a risk factor for [acetaminophen]
hepatotoxicity in alcoholics because a lower dose of [acetaminophen]
will be necessary to deplete glutathione below the critical threshold
concentration where hepatocellular necrosis starts to occur."
Chronic
ethanol and nicotine interaction on rat tissue antioxidant defense
system.
Husain K, Scott BR, Reddy SK, Somani SM. [Alcohol. 2001 Oct;25(2):89-97.]
This study was undertaken to examine the interactive effects of chronic
ethanol and nicotine consumption on the antioxidant defense system
in different tissues of rat. Chronic ingestion of ethanol resulted
in a significant depletion of glutathione (GSH) content in liver,
lung, and testes, whereas chronic administration of nicotine significantly
depleted GSH content in liver and testes. The combination of ethanol
plus nicotine resulted in a significant depletion of GSH content in
liver, lung, and testes. Chronic ingestion of ethanol resulted
in a significant decrease in glutathione peroxidase (GSH-Px) activity
in liver and kidney, whereas a combination of ethanol plus nicotine
increased GSH-Px activity in liver and decreased GSH-Px activity in
kidney and testes. Ethanol, nicotine, or a combination of ethanol
plus nicotine significantly increased lipid peroxidation, respectively,
in liver. It is suggested that prolonged exposure to ethanol and
nicotine produce similar, and in some cases additive, oxidative tissue
injuries in rat.
Treatment
of sulfur mustard (HD)-induced lung injury.
Anderson DR, Byers SL, Vesely KR. [J Appl Toxicol 2000 Dec;20(S1):S129-S132]
An in vivo sulfur mustard (HD) vapor exposure model followed by bronchoalveolar
lavage was developed previously in this laboratory to study biochemical
indicators of HD-induced lung injury. This model was used to test
two treatment compounds-niacinamide (NIA) and N-acetyl cysteine (NAC)-for
their ability to ameliorate HD-induced biochemical changes. These
results show that NAC may be useful as a potential treatment compound
for HD-induced lung injury.
Role
of glutathione redox cycle and catalase in defense against oxidative
stress induced by endosulfan in adrenocortical cells of rainbow trout
(Oncorhynchus mykiss).
Dorval J, Hontela A. [Toxicol Appl Pharmacol. 2003 Oct 15;192(2):191-200.]
The role
of antioxidants in maintaining the functional integrity of adrenocortical
cells during in vitro exposure to endosulfan, an organochlorine pesticide,
was investigated in rainbow trout (Oncorhynchus mykiss). ...protection
against the adrenal toxicity of endosulfan, a pesticide that impairs
cell viabilityand cortisol secretion. CAT, GPx, and GSH were identified
as important antioxidants in maintaining the function and integrity
of rainbow trout adrenocortical cells and ATA, L-BSO, and NAC were
identified as effective modulators of CAT and GSH redox cycle. Moreover,
this study suggests that the glutathione redox cycle may be more efficient
than catalase in protecting adrenocortical cells against endosulfan-induced
oxidative stress.
Toxic
metals and antioxidants: Part II. The role of antioxidants in arsenic
and cadmium toxicity
Patrick L. [Altern Med Rev. 2003 May;8(2):106-28.] Exposure
to toxic metals has become an increasingly recognized source of illness
worldwide. Both cadmium and arsenic are ubiquitous in the environment,
and exposure through food and water as well as occupational sources
can contribute to a well-defined spectrum of disease. The mechanisms
of arsenic- and cadmium-induced damage include the production of free
radicals that alter mitochondrial activity and genetic information.
The metabolism and excretion of these heavy metals depend on the presence
of antioxidants and thiols that aid arsenic methylation and both arsenic
and cadmium metallothionein-binding. S-adenosylmethionine, lipoic
acid, glutathione, selenium, zinc, N-acetylcysteine (NAC), methionine,
cysteine, alpha-tocopherol, and ascorbic acid have specific roles
in the mitigation of heavy metal toxicity. Several antioxidants including
NAC, zinc, methionine, and cysteine, when used in conjunction with
standard chelating agents, can improve the mobilization and excretion
of arsenic and cadmium.
See
also:
Glutathione (GSH): Master Antioxidant and Cellular Detoxifier
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