Hepatotoxicity mechanism

Adinehzadeh M, Reo NV. 1998. Effects of peroxisome proliferators on rat liver phospholipids Sphingomyelin degradation may be involved in hepatotoxic mechanism of perfluorodecanoic acid. Chem Res Toxicol 11 428-440. 

Sturgill, M.G., Lambert, G.H. (1997). Xenobiotic-induced hepatotoxicity mechanisms of liver injury and methods of monitoring hepatic fimction. Clin. Chem. 43 1512-26. 

Obviously, even with a combinatorial assessment of hepatotoxic mechanisms, a relatively simple in vitro system cannot recapitulate all of the mechanisms... 

Sturgill, M. G., and G. H. Lambert. 1997. Xenobiotic-induced hepatotoxicity Mechanisms of liver injury and methods of monitoring hepatic function. Clinical Chemistry 43 1512-1526. 

Nelson, S.D. (1990). Molecular mechanisms of the hepatotox-icity caused by acetaminophen. Semin. Liver Dis. 10, 267-278. 

In the subsequent years, the mechanism of CCU hepatotoxicity has been more fully characterized, although the picture is still not complete. CCU is metabolized by cytochrome P450 in the endoplasmic... 

The present view of the mechanism of acute CCU hepatotoxicity is that it is metabolized by cytochrome P450 to CCI3, a large proportion of which reacts with oxygen to form CCI3OO. Neither radical can leave... 

Thompson, D. C. Perera, K. London, R. Studies on the mechanism of hepatotoxicity of 4-methylphenol(/j-cresol)—effects of deuterium labeling and ring substitution. Chem.-Biol. Interact. 1996, 101, 1-11. 

Black cohosh has been one of the most studied herbal remedies for vasomotor symptoms, and it has not demonstrated a substantial benefit over placebo. The mechanism of action, safety profile, drug-drug interactions, and adverse effects of black cohosh remain unknown. In non-placebo-controlled trials conducted for 6 months or less, black cohosh demonstrated a small reduction in vasomotor symptoms. It has not been shown to be effective for vasomotor symptoms in women with breast cancer.33 There have been case reports of hepatotoxicity with the use of black cohosh.36 Caution should be exercised when considering the use of this product, especially in patients with liver dysfunction. 

Laskin, D.L., Pilaro, A., and Ji, S., Potential role of activated macrophages in acetaminophen hepatotoxicity. II. Mechanism of macrophage accumulation and activation. Toxicol. Appl. Pharmacol., 86, 216, 1986. 

Minocycline is associated with a relatively high incidence of hepatotoxicity. In many cases it is quite distinct from minocycline-induced lupus, occurs earlier in the course of treatment (about 1 month), and the mechanism is unknown [62], However, in some cases the liver toxicity merges with the lupus-like syndrome, occurring after about a year of therapy, and is associated with ANA. This form is indistinguishable from idiopathic autoimmune hepatitis [63], and antibodies against Cyp 3A6 and Cyp 2C4 have been reported [64], Diclofenac has also been reported to cause hepatitis with autoimmune features such as ANA [65],... 

Satoh, H. et al., Immunological studies on the mechanism of halothane-induced hepatotoxicity Immunohistochemical evidence of trifluoroacetylated hepatocytes, J. Pharmacol. Exp. Ther., 233, 857, 1985. 

No information is available on the adverse health effects of hexachloroethane in humans. Animal studies revealed that hexachloroethane primarily causes liver and kidney toxicity. Effects on the nervous system and lungs have also been reported. The mechanism by which these effects are mediated is not well characterized. Reductive metabolism by cytochrome P-450 and production of a free radical intermediate have been suggested as factors in hexachloroethane-induced hepatotoxicity (Nastainczyk et al. 1982a Thompson et al. 1984 Town and Leibman 1984). Accordingly, one possible approach may be to reduce free radical injury. To that end, oral administration of N-acetylcysteine can be used as a means of reducing free radical injury. Also, oral administration of vitamin E and vitamin C may be of value since they are free radical scavengers. 

Primary hepatocyte cultures have been used as a tool to predict the hepatotoxicity of many compounds such as nonsteroidal anti-inflammatory drugs (Castell et ah, 1988), psychotropic drugs (Boelsterli et ah, 1987), immunosuppressant drugs (Boelsterli et ah, 1988), and salicylates (Tolman et ah, 1978). Rat primary hepatocyte cultures have also been shown to be a good model for examining the mechanisms of metallothionein-induced tolerance to cadmium toxicity (Liu et ah,... 

Several mechanisms of fialuridine-induced hepatotoxicity have been suggested fialuridine and its metabolites inhibit mitochondrial DNA replication, leading to decreased mitochondrial DNA and mitochondrial ultrastructural defects [61]. Another mechanism suggested lies in pyruvate oxidation inhibition [62]. 

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