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Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite.
TLDR
A dose threshold exists for bromobenzene-induced hepatic necrosis and it is demonstrated that the hepatotoxic metabolite is preferentially conjugated (detoxified) with glutathione, thereby depleting glutATHione from the liver.
Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione.
TLDR
A fundamental role of glutathione in the body may be to protect tissues against electrophilic attack by drug metabolites and other alkylating agents.
Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism.
TLDR
It is proposed thatacetaminophen-induced hepatic necrosis is mediated by a toxic metabolite of acetaminophen, which inhibits synthesis of cytochrome P-450 and thereby prevented the hepatic damage.
Acetaminophen-induced hepatic necrosis. II. Role of covalent binding in vivo.
TLDR
It is proposed that acetaminophen-induced hepatic necrosis may be caused by the covalent binding of a chemically reactive metabolite to vital hepatsic macromolecules.
Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis.
The clinical spectrum of isoniazid-induced liver injury seems to be clinically, biochemically, and histologically indistinguishable from viral hepatitis, except that the injury occurs primarily in
Effects of N-acetylcysteine on acetaminophen covalent binding and hepatic necrosis in mice.
TLDR
The hypothesis that sulfhydryl nucleophiles such as N-acetylcysteine act primarily through prearylation mechanisms to decrease the amount of reactive metabolite available for initiation of hepatic injury is supported.
Mechanism of action of N-acetylcysteine in the protection against the hepatotoxicity of acetaminophen in rats in vivo.
TLDR
Exogenous N-acetylcysteine does not form significant amounts of conjugate with the reactive metabolite of acetaminophen in the rat in vivo but increases glutathione synthesis, thus providing more substrate for the detoxification of the reactive metabolismite in the early phase of an acetamophen intoxication when the critical reaction with vital macromolecules occurs.
Evidence that acetaminophen and N-hydroxyacetaminophen form a common arylating intermediate, N-acetyl-p-benzoquinoneimine.
TLDR
Observations provide strong evidence that the reactive intermediate formed in microsomes from acetarninophen and in solution from N-hydroxyacetaminophen is N-acetyl-p-benzoquinoneimine.
Effects of chronic central nervous system administration of agouti-related protein in pair-fed animals.
TLDR
It is demonstrated that independent of its orexigenic effects, chronic AGRP treatment decreased BAT UCP-1, suppressed plasma TSH, and increased fat mass and plasma leptin, suggesting that it may play a role in energy expenditure.
Effects of N-acetylcysteine on the disposition and metabolism of acetaminophen in mice.
TLDR
Treatment of mice with N-acetylcysteine was found to prevent the hepatic damage caused by 1000 mg/kg p.o. of acetaminophen, and results are incompatible with a decreased formation of the toxic species secondary to delayed acetamophen absorption from the gastrointestinal tract or with an increased clearance of acetamine via nontoxic pathways such as sulfation.
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