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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.1
- 수록면
- 112 - 121 (10page)
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초록· 키워드
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Drug-induced liver injury (DILI) is the serious and fatal drug-associated adverse effect, but its incidence is very low and individual variation in severity is substantial. Acetaminophen (APAP)-induced liver injury accounts for >50% of reported DILI cases but little is known for the cause of individual variations in the severity. Intrinsic genetic variation is considered a key element but the identity of the genes was not well-established. Here, pre-biopsy method and microarray technique was applied to uncover the key genes for APAP-induced liver injury in mice, and a cause and effect experiment employing quantitative real-time PCR was conducted to confirm the correlation between the uncovered genes and APAP-induced hepatotoxicity. We identified the innately and differentially expressed genes of mice susceptible to APAP-induced hepatotoxicity in the pre-biopsied liver tissue before APAP treatment through microarray analysis of the global gene expression profiles (Affymetrix $GeneChip^{(R)}$ Mouse Gene 1.0 ST for 28,853 genes). Expression of 16 genes including Gdap10, Lpl, Gabra3 and Ccrn4l were significantly different (t-test: FDR <10%) more than 1.5 fold in the susceptible animals than resistant. To confirm the association with the susceptibility to APAP-induced hepatotoxicity, another set of animals were measured for the expression level of selected 4 genes (higher two and lower two genes) in the liver pre-biopsy and their sensitivity to APAP-induced hepatotoxicity was evaluated by post hoc. Notably, the expressions of Gabra3 and Lpl were significantly correlated with the severity of liver injury (p<0.05) demonstrating that these genes may be linked to the susceptibility to APAP-induced hepatotoxicity.
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등록된 정보가 없습니다.
참고문헌 (42)
참고문헌 신청
Baron, A. D. / 1988 / Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans / Am. J. Physiol 255:E769~E774
Bessems, J. G. / 2001 / Paracetamol (acetaminophen)-induced toxicity: molecular and biochemical mechanisms, analogues and protective approaches / Crit. Rev. Toxicol 31:55~138
Biju, M. P. / 2001 / Hepatic GABA(A) receptor functional regulation during rat liver cell proliferation / Hepatol. Res 21:136~146
Bozogluer, E. / 2012 / The effect of different doses of flumazenil on acetaminophen toxicity in rats / Bratisl. Lek. Listy 113:525~528
Chang, C. Y. / 2007 / Review article: drug hepatotoxicity / Aliment. Pharmacol. Ther 25:1135~1151
Bessems, J. G. / 2001 / Paracetamol (acetaminophen)-induced toxicity: molecular and biochemical mechanisms, analogues and protective approaches / Crit. Rev. Toxicol 31:55~138
Biju, M. P. / 2001 / Hepatic GABA(A) receptor functional regulation during rat liver cell proliferation / Hepatol. Res 21:136~146
Bozogluer, E. / 2012 / The effect of different doses of flumazenil on acetaminophen toxicity in rats / Bratisl. Lek. Listy 113:525~528
Chang, C. Y. / 2007 / Review article: drug hepatotoxicity / Aliment. Pharmacol. Ther 25:1135~1151
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