Hepatotoxic principle

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). 

The most important of the peptidic phosphatase inhibitors are the microcystins and nodularin. Mycrocystins are heptapeptides characterised by the sequence cyclo(D-Ala-X-D-e/7t/i/ o-P-methylisoAsp-Y-Adda-D-isoGlu-iV-methyldehydroAla), where X and Y are different L-aminoacids, and Adda is the abbreviation of the P-aminoacid [25,35,85,95]-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4(E),6(E)-dienoic acid. In the most common microcystin, namely microcystin-LR, X is Leu and Y is Arg. This kind of compounds was considered to be the highly hepatotoxic principle of the cyanobacteria genera Microcystis, Artabaena and Oscillatoria. Apart Jfrom the variations represented by X and Y, other differences arising jfrom the demethylation of aminoacids, lead to the existence to more than fifty microcystins. The rare acid Adda is also... 

Strictly speaking, an acute toxicity study is conducted to examine the effect of a single dose of a single compound. In designing specific toxicity screens, however, deviation from this principle is permissible if it increases screen sensitivity. For example, the sensitivity of mice to many indirect hepatotoxins will be enhanced by prior treatment with phenobarbital. Hence, the sensitivity of a hepatotoxicity screen will be enhanced if the mice are pretreated for three days with phenobarbital. 

Bruckner JV, Kim HJ, Muralidhara S, et al. 1990. Influence of route and pattern exposure on the pharmacokinetics and hepatotoxicity of carbon tetrachloride. In Gerrity TR and Henry CJ, eds. Principle of route to route extrapolation for risk assessment. Elsevier Science Publishing Co., Inc. 271-284. 

The cyanobacterium Cylindrospermopsis raciborskii, which is normally nontoxic, was found to be responsible for the outbreak of a hepatoenteritis epidemic on Palm Island, Queensland, Australia. The active principle proved to be the strongly hepatotoxic, tricyclic guanidinederivativeC. (C 5H2 N507S,Mr415.43, [a]p -31°). C. presumably exists in a lactim form. 

Pari, L. and Amali, D.R. 2005. Protective role of tetrahydrocurcumin (THC) an active principle of turmeric on chloroquine induced hepatotoxicity in rats. J. Pharm. Pharm. Sci., 8 115-123. 

Use discouraged due to potential presence of hepatotoxic pyrrolizidine alkaloids ubiquitous in Eupatorium species (newall). Abortion in cattle grazing on the plant is attributed to a high content of nitrate. Toxic principles are believed to include eupatorin (cytotoxic, emetic), bitter components (gastrointestinal irritants), and lactones (skin sensitizers) (brinker). 

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