Dataset Information

An effective assessment of simvastatin-induced toxicity with NMR-based metabonomics approach.

ABSTRACT:

Background

Simvastatin, which is used to control elevated cholesterol levels, is one of the most widely prescribed drugs. However, a daily excessive dose can induce drug-toxicity, especially in muscle and liver. Current markers for toxicity reflect mostly the late stages of tissue damage; thus, more efficient methods of toxicity evaluation are desired.

Methodology/principal findings

As a new way to evaluate toxicity, we performed NMR-based metabonomics analysis of urine samples. Compared to conventional markers, such as AST, ALT, and CK, the urine metabolic profile provided clearer distinction between the pre- and post-treatment groups treated with toxic levels of simvastatin. Through multivariate statistical analysis, we identified marker metabolites associated with the toxicity. Importantly, we observed that the treatment group could be further categorized into two subgroups based on the NMR profiles: weak toxicity (WT) and high toxicity (HT). The distinction between these two groups was confirmed by the enzyme values and histopathological exams. Time-dependent studies showed that the toxicity at 10 days could be reliably predicted from the metabolic profiles at 6 days.

Conclusions/significance

This metabonomics approach may provide a non-invasive and effective way to evaluate the simvastatin-induced toxicity in a manner that can complement current measures. The approach is expected to find broader application in other drug-induced toxicity assessments.

SUBMITTER: Yang HJ

PROVIDER: S-EPMC3043067 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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An effective assessment of simvastatin-induced toxicity with NMR-based metabonomics approach.

Yang Hye-Ji HJ Choi Myung-Joo MJ Wen He H Kwon Hyuk Nam HN Jung Kyung Hee KH Hong Sang-Won SW Kim Joon Mee JM Hong Soon-Sun SS Park Sunghyouk S

PloS one 20110222 2

<h4>Background</h4>Simvastatin, which is used to control elevated cholesterol levels, is one of the most widely prescribed drugs. However, a daily excessive dose can induce drug-toxicity, especially in muscle and liver. Current markers for toxicity reflect mostly the late stages of tissue damage; thus, more efficient methods of toxicity evaluation are desired.<h4>Methodology/principal findings</h4>As a new way to evaluate toxicity, we performed NMR-based metabonomics analysis of urine samples. C ...[more]

PMID: 21364936

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Dataset Information

An effective assessment of simvastatin-induced toxicity with NMR-based metabonomics approach.

Background

Methodology/principal findings

Conclusions/significance

Publications

An effective assessment of simvastatin-induced toxicity with NMR-based metabonomics approach.

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