title: Oxidative stress-mediated developmental toxicity induced by isoniazide in zebrafish embryos and larvae.
abstract: Isoniazide (INH) is an important first-line drug that is used to treat tuberculosis. However, the effect of INH on fetal growth has not yet been elucidated, and the mechanism of INH-induced developmental toxicity is still unknown. In the present study, we employed zebrafish embryos and larvae to investigate the developmental toxicity of INH. The survival rates of the embryos and larvae as well as the hatching rates of embryos were significantly reduced. Morphological abnormalities, including spinal curvature, yolk retention, swimming bladder absence, tail bending and shorter body lengths were induced by INH. Histopathological analysis showed loose cell-to-cell contacts and large vacuoles in the larval hepatocytes. Thin intestinal walls, frayed gut villi and widespread cell lysis were observed in the intestines of the larvae in the higher concentration (8, 16 mm) exposure groups. In addition, exposure to high doses (≥ 6 mm) of INH significantly reduced the locomotor capacity of the zebrafish larvae. INH significantly increased the levels of reactive oxygen species and malondialdehyde and decreased the superoxide dismutase activity in zebrafish larvae, which suggested that oxidative stress was induced and that the antioxidant capacity was inhibited. Superoxide dismutase 1 and liver fatty acid-binding protein mRNA levels were significantly downregulated, while the GSTP2 and cytochrome P450 3A mRNA levels were significantly upregulated in the INH-exposed zebrafish larvae. The overall results indicated that INH caused a dose- and time-dependent increase in developmental toxicity and that oxidative stress played an important role in the developmental toxicity induced by INH in zebrafish larvae. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng, 475004, Henan Province, People's Republic of China.|Biology Institute of Shandong Academy of Sciences, 19 Keyuan Road, Lixia District, Jinan, 250014, Shandong Province, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Biology Institute of Shandong Academy of Sciences, 19 Keyuan Road, Lixia District, Jinan, 250014, Shandong Province, People's Republic of China.|Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, 19 Keyuan Road, Lixia District, Jinan, 250014, Shandong Province, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Biology Institute of Shandong Academy of Sciences, 19 Keyuan Road, Lixia District, Jinan, 250014, Shandong Province, People's Republic of China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Han
authors.affiliation: Biology Institute of Shandong Academy of Sciences, 19 Keyuan Road, Lixia District, Jinan, 250014, Shandong Province, People's Republic of China.|Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, 19 Keyuan Road, Lixia District, Jinan, 250014, Shandong Province, People's Republic of China.
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: He
authors.affiliation: Biology Institute of Shandong Academy of Sciences, 19 Keyuan Road, Lixia District, Jinan, 250014, Shandong Province, People's Republic of China.|Shandong Provincial Engineering Laboratory for Biological Testing Technology, 19 Keyuan Road, Lixia District, Jinan, 250014, Shandong Province, People's Republic of China.
authors.forename: Hairong
authors.initials: H
authors.lastname: Hou
authors.affiliation: Biology Institute of Shandong Academy of Sciences, 19 Keyuan Road, Lixia District, Jinan, 250014, Shandong Province, People's Republic of China.|Key Laboratory for Biosensor of Shandong Province, 19 Keyuan Road, Lixia District, Jinan, 250014, Shandong Province, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Han
authors.affiliation: Biology Institute of Shandong Academy of Sciences, 19 Keyuan Road, Lixia District, Jinan, 250014, Shandong Province, People's Republic of China.|Shandong Provincial Engineering Laboratory for Biological Testing Technology, 19 Keyuan Road, Lixia District, Jinan, 250014, Shandong Province, People's Republic of China.|Key Laboratory for Biosensor of Shandong Province, 19 Keyuan Road, Lixia District, Jinan, 250014, Shandong Province, People's Republic of China.
authors.forename: Ximin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Ecology Institute of Shandong Academy of Sciences, 19 Keyuan Road, Lixia District, Jinan, 250014, Shandong Province, People's Republic of China.
authors.forename: Chengyun
authors.initials: C
authors.lastname: Li
authors.affiliation: Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng, 475004, Henan Province, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Cen
authors.affiliation: Biology Institute of Shandong Academy of Sciences, 19 Keyuan Road, Lixia District, Jinan, 250014, Shandong Province, People's Republic of China.|Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, 19 Keyuan Road, Lixia District, Jinan, 250014, Shandong Province, People's Republic of China.|Key Laboratory for Biosensor of Shandong Province, 19 Keyuan Road, Lixia District, Jinan, 250014, Shandong Province, People's Republic of China.
authors.forename: Kechun
authors.initials: K
authors.lastname: Liu
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects*; D006801:Humans; D007538:Isoniazid / Q000633:toxicity*; D007814:Larva / Q000187:drug effects*; D023421:Models, Animal; D018384:Oxidative Stress / Q000187:drug effects*; D015027:Zebrafish / Q000254:growth & development*
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid
keywords: Isoniazide; developmental toxicity; oxidative stress; swimming behavior; zebrafish embryos; zebrafish larvae