title: Crosstalk between E2f1 and c-Myc mediates hepato-protective effect of royal jelly on taxol-induced damages.
abstract: Previous histopathological studies have shown the hepatotoxicity of paclitaxel (TXL). However, there is little known about the molecular pathway(s) of TXL-induced hepatotoxicity. Therefore, this study aimed to uncover the role of two transcription factors in the TXL-induced hepatotoxicity. Moreover, the hepato-protective effect of royal jelly (RJ) on TXL-induced toxicity was investigated. Wistar rats were divided into control and test groups. The test groups along with TXL received various doses of RJ (0, 50, 100 and 150 mg/kg, body weight). Biochemical hepatic functional assays, histopathological studies and hepatic superoxide dismutase level were determined. Additionally, the expression of E2f1 and cellular-myelocytomatosis (c-Myc) at messenger RNA (mRNA) level in the liver was evaluated. The hepatic functional biomarkers showed a significant ( p < 0.05) elevation in the TXL-received animals, while RJ administration for 28 days resulted in a remarkable reduction in TXL-elevated alkaline phosphatase, alanine transaminase and lactate dehydrogenase levels. The TXL-treated animals showed a significant ( p < 0.05) up-regulation of E2f1 and down-regulation of c-Myc at mRNA level, respectively. RJ lowered the expression of E2f1 while enhanced the expression of c-Myc in a dose-dependent manner. Our data suggest the hepato-protective effects of RJ on TXL-induced toxicity, which may attribute to a clear crosstalk between E2f1 and c-Myc as two regulators of liver growth.
authors: 1 Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Urmia University, Urmia, Islamic Republic of Iran.|2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Islamic Republic of Iran.
authors: H
authors: H
authors: Malekinejad
authors: 2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Islamic Republic of Iran.
authors: M
authors: M
authors: Fani
authors: 2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Islamic Republic of Iran.
authors: S Kh
authors: SK
authors: Shafiee-Roodbari
authors: 3 Department of Pathology, Faculty of Veterinary Medicine, Urmia University, Urmia, Islamic Republic of Iran.
authors: F
authors: F
authors: Delkhosh-Kasmaie
authors: 4 Department of Embryology and Histology, Faculty of Veterinary Medicine, Urmia University, Urmia, Islamic Republic of Iran.
authors: A
authors: A
authors: Rezaei-Golmisheh
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D050687:E2F1 Transcription Factor / Q000235:genetics; D005227:Fatty Acids / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D017239:Paclitaxel / Q000633:toxicity*; D020011:Protective Agents / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D000099219:Royal Jelly
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D050687:E2F1 Transcription Factor; D005227:Fatty Acids; D007770:L-Lactate Dehydrogenase; D009569:Nitric Oxide; D017239:Paclitaxel; D020011:Protective Agents; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D000099219:Royal Jelly; C493755:E2f1 protein, rat
keywords: Cell signalling; hepatic functional tests; hepatotoxicity; transcriptional factor