Toxicity liver

Yellow phosphorus was the first identified liver toxin. It causes accumulation of lipids in the liver. Several liver toxins such as chloroform, carbon tetrachloride, and bromobenzene have since been identified. I he forms of acute liver toxicity are accumulation of lipids in the liver, hepartxiellular necrosis, iii-trahepatic cholestasis, and a disease state that resembles viral hepatitis. The types of chrome hepatotoxicity are cirrhosis and liver cancer. 

Accumulation of lipids in the liver (steatosis) is one possible mechanism for liver toxicity. Several compounds causing necrosis of hepatocytes also cause steatosis. There are, however, some doubts that steatosis would be the primary cause of liver injury. Several compounds cause steatosis (e.g., puro-mycin, cycloheximide) without causing liver injury. Most of the accumulated lipids are triglycerides. In steatosis, the balance between the synthesis and excretion of these lipids has been disturbed (see Table 5.13). 

The most common adverse effects are myelosuppression, with leukopenia and thrombocytopenia appearing 7-10 days after treatment, as well as mild nausea. Liver toxicity with jaundice has been reported in rare cases. 

Pain, headache, asthenia, abdominal pain, chest pain, flu symptoms, fever, liver toxicity, insomnia, nausea, constipation, testicular atrophy, dyspnea, pain, asthenia... 

Ehrhardt A, Xu H, Dillow AM, Bellinger DA, Nichols TC, Kay MA (2003) A gene-deleted adenoviral vector results in phenotypic correction of canine hemophilia B without liver toxicity or thrombocytopenia. Blood 102 2403-2411... 

Peroxidation of lipids is another factor which must be considered in the safety evaluation of liposome administration. Smith and coworkers (1983) demonstrated that lipid peroxides can play an important role in liver toxicity. Allen et al. (1984) showed that liposomes protected by an antioxidant caused less MPS impairment than liposomes subjected to mild oxidizing conditions. From the study of Kunimoto et al. (1981) it can be concluded that the level of peroxidation in freshly prepared liposome preparations and those on storage strongly depends both on the phospholipid fatty acid composition and on the head group of the phospholipid. Addition of appropriate antioxidants to liposomes composed of lipids which are liable to peroxidation and designed for use in human studies is therefore necessary. 

One of the compounds was previously tested for toxicology and was found to have no liver toxicity... 

The mechanism of action for liver toxicity and carcinogenicity may involve the formation of reactive products (Bonse and Henschler 1976 Bonse et al. 1975 Fisher et al. 1991 Larson and Bull 1992b). Methods for reducing the destructive damage caused by these intermediates, or for blocking their formation through inhibition of metabolic pathways may prove effective in reducing hepatic toxicity but are not currently available for clinical use. 

Liver toxicity, as evidenced by alterations in the incorporation of lysine into liver proteins, was observed in rats administered 192 mg lead/kg/day by gavage as lead acetate for 9 weeks (Barratt et al. 1989). No effects were observed at 21 mg lead/kg/day. However, the toxicological significance of this finding is not known because neither serum enzymes nor histopathological evaluations were performed. 

Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, Mackenzie KI, La-Tour A et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci USA 2001 98(6) 3 369 3374. 

I 12. The answer is b. (Hardman, pp 1264-1265J Dactinomycin s major toxicities include stomatitis, alopecia, and bone marrow depression. Bleomycin s toxicities include edema of the hands, alopecia, and stomatitis. Mitomycin causes marked bone marrow depression, renal toxicity, and interstitial pneumonitis. Plicamycin causes thrombocytopenia, leukopenia, liver toxicity, and hypocalcemia. The latter may be of use in the treatment of hypercalcemia. Doxorubicin causes cardiotoxicity, as well as alopecia and bone marrow depression. The cardiotoxicity has been linked to a lipid peroxidation within cardiac cells. 

The answer is c. (Hardman, pp 632-633.) Nausea, vomiting, abdominal pain, and diarrhea are early signs of the severe liver toxicity caused by high levels of acetaminophen other symptoms of acetaminophen toxicity include dizziness, excitement, and disorientation. N-acetyl-L-cysteine is the appropriate treatment for acetaminophen overdose. 

The drug may cause liver toxicity and is contraindicated in patients with preexisting liver disease. The ALT should be monitored monthly initially and periodically thereafter. Leflunomide may cause bone marrow toxicity a complete blood cell count with platelets is recommended monthly for 6 months and then every 6 to 8 weeks thereafter. It is teratogenic and should be avoided during pregnancy. 

The starting and recommended dose of tolcapone is 100 mg three times daily as an adjunct to carbidopa/L-dopa. Its use is limited by the potential for fatal liver toxicity. Strict monitoring of liver function is required, and tolcapone should be discontinued if liver function tests are above the upper limit of normal or any signs or symptoms suggestive of hepatic failure exist. It should be reserved for patients with fluctuations that have not responded to other therapies. 

Laskin, D.L. et al., Prooxidant and antioxidant functions of nitric oxide in liver toxicity, Antioxid. Redox. Signal, 3, 261, 2001. 

Thiono and sulfhydryl drugs are also associated with a significant incidence of a lupus-like syndrome. Propylthiouracil is associated with a significant incidence of lupus [18] as well as liver toxicity [19, 20] and agranulocytosis [21], Penicillamine is associated with lupus, agranulocytosis [22] and a variety of autoimmune syndromes as discussed later. 

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],... 

Chronic-Duration Exposure and Cancer. No studies were located in humans following chrome-duration exposure to hexachloroethane for any exposure route. No chronic animal studies were conducted using the inhalation route of exposure. In oral studies with rats, the kidney was identified as a primary target organ in males and females (NTP 1989). The kidney damage in male rats was the result of hyaline droplet nephropathy and, accordingly, was not suitable as the basis for an oral MRL. In contrast to acute- and intermediate-duration oral exposure, liver toxicity was not evident in rats following chronic oral exposure. There were no studies of chronic dermal exposure to hexachloroethane. 

Smith KS, Smith PL, Heady TN, et al. In vitro metabolism of tolcapone to reactive intermediates relevance to tolcapone liver toxicity. Chem Res Toxicol 2003 16(2) 123—128. 

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