Anti-hepatotoxic effects

The best evidences are studies from preclinical animal models [86, 87, 105], or knockout animals lacking appropriate anti-oxidative pathways [106]. For example, Balb/c mice administered a variety of anti-oxidants in their chow were protected from acetaminophen hepatotoxicity [107]. Rats fed with the anti-oxidant melatonin were protected from cholesterol mediated oxidative liver damage [108]. The best clinical evidence that oxidative stress is a key player in a variety of liver injury diseases is the beneficial application of silymarin in these disease indications [109]. Silymarin is a polyphenolic plant fiavonoid (a mixture of flavonoid isomers such as silibinin, isosilibinin, silidianin and silichristin) derived from Silymarin maria-num that has antioxidative, antilipid peroxidative, antifibrotic and anti-inflammatory effects [109, 110]. 

Coltsfoot Upper respiratory tract infections Pyrrolizidine alkaloids, hepatotoxicity Avoid ingestion of any parts of plant leaves may be used topically for anti-inflammatory effects for up to 4-6 weeks... 

Comfrey (Symphytum officinale) Uses Topical treatment of wounds, bruises, sprains, inflammation Action Multiple chemical components, allantoin promotes cell division, rosmarinic acid has anti-inflammatory effects, tannin possesses astringent effects, mucilage is a demulcent w/ anti-inflammatory properties, pyrrolizidine alkaloids cause hepatotox Available forms Topical application w/ 5—20% of herb applied on intact skin for up to 10 d Contra Do not take orally d/t hepatotox, do not use if PRG or w/ lactation Notes/SE N/V, exfoliative dermatitis w/ topical use Interactions T Risk of hepatotox W/ ingestion of borage, golden ragwort, hemp, Petasites EMS None... 

Soyasaponin I (1) inhibited the elevation of aspartate aminotransferase (AST) activity, which was comparable to that of glycyrrhizin (positive control). On the other hand, Kaikasaponin HI (21) was more effective than 1. Compound 21 showed antihepatotoxic activity at less than 100p.g/ml. Furthermore, the highest activity was observed even at lower doses (50, 100pg/ml). Therefore, sophoradiol OGs were concluded to be the anti-hepatotoxic principle in both crude drugs (Abri Heba and Puerariae Flos). 

Danazol is a weak androgen and also has a series of other hormonal and anti-hormonal properties. It inhibits pituitary gonadotropin and has been used in the treatment of endometriosis, fibrocystic disease of the breast, idiopathic thrombocytopenic purpura, and hereditary angioedema. Its hepatotoxic effects include reversible rises in serum transaminases and cholestatic hepatitis a few cases of hepatocellular tumors have been reported. 

Metabolism of the anti-malarial amodiaquine provides quinone-imine, which is an electrophilic metabolite responsible for hepatotoxicity and agranulocytosis. These side effects have severely restricted the clinical use of amodiaquine. The replacement of the phenolic hydroxyl by a fluorine prevents from oxidation process. Then, the A/-dealkylation becomes the major process. This has led to further refinements, with the preparation of the A/-f-butyl analogue, a compound which resists towards metabolic side-chain cleavage and has an excellent in vitro and in vivo profile (Fig. 15) [56]. 

Flucytosine is converted into the anti metabolite 5-fluorouracil that inhibits thymidilate synthetase, thereby disrupting DNA synthesis. It also interferes with protein synthesis by incorporation of fluorouracil into RNA in place of uracil. Although active against most Candida species, its spectrum of antifungal activity, overall, is narrow. Since resistance can develop rapidly it is usually coadministered with another agent and its main value is that it facilitates a reduction in the dose (and, presumably, the toxic effect) of amphotericin when co-prescribed in this way. The main adverse effects are marrow aplasia and hepatotoxicity. 

Anti metabolites are structural analogues of normal cellular constituents that interfere with the synthesis of purine and pyrimidine, which are essential for DNA synthesis and cell division. They are used in the treatment of gastrointestinal and pulmonary carcinomas as well as sarcomas and some leukaemias. The major toxic effects are bone marrow suppression, mucositis, severe diarrhoea, nausea and vomiting. They have been associated with acute and chronic hepatotoxicity. 

Consistent with the monkey data, PS ODN and 2 -MOE ASO have been largely absent of hepatotoxicity in clinical trials [47,48,64,65].The only notable exception was the report of mild and transient increases in ALT of patients treated with anti-HIV PS ODN, GEM 91 [66]. This was also likely attributable to the proinflammatory effects that were present for this early generation of ASO comprised of 27 nucleotide residues along with CpG motiffs. 

CICLOSPORIN VASODILATOR ANTI HYPERTENSIVES 1. Co-administration of bosentan and ciclosporin leads to t bosentan and 1 ciclosporin levels 2. Risk of hypertrichosis when minoxidil is given with ciclosporin 3. t sitaxentan levels 1. Additive effect both drugs inhibit the bile sodium export pump, which is associated with hepatotoxicity 2. Additive effect 3. Uncertain 1. Avoid co-administration of bosentan and ciclosporin 2. Warn patients of the potential interaction 3. Avoid co-administration... 

Forrester S D, Troy G C 1999 Renal effects of nonsteroidal anti-inflammatory drugs. Compendium on Continuing Education for the Practicing Veterinarian 21 910-919 Fry S W, Seeff L B 1995 Hepatotoxicity of analgesics and anti-inflammatory agents. Gastroenterology Clinics of North America 24 875-905... 

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