title: Corn oil as a vehicle in drug development exerts a dose-dependent effect on gene expression profiles in rat thymus.
abstract: The purpose of this study was to investigate the effects of corn oil (CO), which is widely used as a vehicle for water-insoluble agents in drug development, on the gene expression profiles in rat thymus with microarray technique. Female Wistar rats were administered daily with normal saline (NS) and CO 2, 5 and 10 ml kg⁻¹ per day for 14 days, respectively. Then, the thymus samples of rats were collected for microarray test and histopathology examination. CD4⁺ and CD8⁺ lymphocytes in peripheral blood were also numerated to assess the effects on lymphocyte subpopulations. The microarray data showed that the numbers of differentially expressed genes in the 2, 5 and 10 ml kg⁻¹ CO groups were 0, 40 and 458, respectively, compared with the NS control group. The altered genes were mainly associated with immune response, cellular response to organic cyclic substance and regulation of fatty acid β-oxidation. However, no abnormal changes in thymus weight, CD4⁺ and CD8⁺ lymphocytes counts and histopathological examination were observed in the three CO groups. These data showed that 10 ml kg⁻¹ CO, the usually recommended dosing volume as a vehicle in drug safety assessment, caused obvious dysregulated genes in rat thymus. Our study suggests that the appropriate dosing volume of CO gavage as a vehicle for water-insoluble agents in drug development should be 2 ml kg⁻¹ per day, if agent effects on thymus will be assessed in gene levels.
authors: Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors: Xing-Chao
authors: XC
authors: Geng
authors: Bo
authors: B
authors: Li
authors: Liang
authors: L
authors: Zhang
authors: Ying
authors: Y
authors: Song
authors: Zhi
authors: Z
authors: Lin
authors: Ying-Qi
authors: YQ
authors: Zhang
authors: Jun-Zhi
authors: JZ
authors: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016516:CD4-CD8 Ratio; D003314:Corn Oil / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020411:Oligonucleotide Array Sequence Analysis; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014677:Pharmaceutical Vehicles; D012333:RNA, Messenger; D003314:Corn Oil