title: Inhibition of GHRH aggravated acetaminophen-induced acute mice liver injury through GH/IGF-I axis.
abstract: The aim of the current study is to investigate the effects of growth hormone releasing hormone (GHRH) antagonist on acetaminophen (APAP)-induced acute liver injury in mice.  Healthy C57/B6L mice were orally treated with 200 mg/kg APAP with or without a 30-min pre-treatment with 300 µg/kg GHRH antagonist MZ-5-156.  After 12 hours, serum, plasma, and liver samples from each mouse were collected for analyses.  Our results showed that twelve-hour treatment with APAP caused obvious liver injury, elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, increased oxidative stress, reduced expressions of antioxidant enzymes, accumulated expression of pro-inflammatory cytokines, and increased circulating levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I).  Pre-treatment with MZ-5-156 aggravated liver injury, further increased serum ALT and AST levels, exacerbated oxidative stress and inflammation induced by APAP.  Treatment of MZ-5-156 also blocked the phosphorylation form and total form of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5).  Treatment of GHRH super-agonist JI-38 immediately after MZ-5-156 treatment partly reversed the liver injury caused by APAP and MZ-5-156.  In conclusion, GHRH plays essential protective role in APAP-induced acute liver injury in vivo.  The protective properties of GHRH are partially through GH/IGF-I axis and JAK/STAT pathway.
authors.affiliation: First affiliated hospital, Xinxiang Medical University, Henan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Hai
authors.forename: Xuehui
authors.initials: X
authors.lastname: Chen
authors.forename: Hua
authors.initials: H
authors.lastname: Peng
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.forename: Lake
authors.initials: L
authors.lastname: Li
authors.forename: Qinggui
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000082:Acetaminophen; D000208:Acute Disease; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors*; D006727:Hormone Antagonists / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017337:Sermorelin / Q000031:analogs & derivatives / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D006727:Hormone Antagonists; C106656:MZ 5-156; D000082:Acetaminophen; D007334:Insulin-Like Growth Factor I; D017337:Sermorelin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone