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Involvement of Histone Hypoacetylation in INH-induced Rat Liver Injury


Abstract: This study explored the mechanism of histone acetylation under oxidative stress in rat liver injury induced by isoniazid (INH). Fifty-six adult Sprague–Dawley rats were selected and divided randomly into INH groups (48) and control (8). Rats in INH groups were intragastrically injected with 55 mg per kg of body weight per day for 3, 7, 10, 14, 21, and 28 days, whereas control rats were given corresponding volumes of distilled water. Pathological changes in liver tissues were observed by hematoxylin and eosin staining. Western blot analysis was conducted to measure the expression levels of H3k14ac and H4k8ac. Activities of HAT, HDAC and IL-1β, and TNF-α were detected by ELISA in liver tissues. Real-time RT-PCR analysis was performed to determine the protein expression levels of HAT, HDAC, and IL-1β, and the mRNA expression of TNF-α. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver tissues were assayed using a biochemical method. At different time points, SOD activity decreased, whereas MDA content significantly increased after 14 days (FSOD = 11.15, FMDA = 7.42, P < 0.01). During this period, the INH group showed decreased histone-acetylated H3K14 expression and H4K8 acetylation (FH3K14 = 4.18, FH4K8 = 3.87, P < 0.05) and higher expression levels of HDAC1 and HDAC2 (FHDAC1 = 29.13, FHDAC2 = 58.34, P < 0.01) compared with those in the control group. Moreover, the expression of CBP/P300 was lower than that in the control group (FCBP/P300 = 12.18, P = 0.001), and the protein contents of IL-1β and TNF-α in rat liver tissues were up-regulated (FIL-1β = 44.88, FTNF-α = 41.56, P < 0.01). These results suggested that histone acetylation is involved in INH-induced rat liver injury. Furthermore, hypoacetylation of histone H3K14 and H4K8 is negatively correlated with oxidative stress-mediated rat liver injury.

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Publication details

The article was received on 08 Jun 2017, accepted on 27 Sep 2017 and first published on 04 Oct 2017

Article type: Paper
DOI: 10.1039/C7TX00166E
Citation: Toxicol. Res., 2017, Accepted Manuscript
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    Involvement of Histone Hypoacetylation in INH-induced Rat Liver Injury

    L. Zhu, Q. Ren, Y. Li, Y. Zhang, J. Li, Y. Li, Z. Shi and F. Feng, Toxicol. Res., 2017, Accepted Manuscript , DOI: 10.1039/C7TX00166E

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