Co-administration of cyclosporine an alleviates thioacetamide-induced liver injury.
OBJECTIVE
To investigate the effects of cyclosporine A (CsA) on thioacetamide (TAA)-induced liver injury.


METHODS
CsA was co-administrated (7.5 microg/kg body weight per day, i.p.) into rat to investigate the role of CsA on TAA-(200 mg/kg body weight per 3 d for 30 d, i.p.)induced liver injury.


RESULTS
The data show that TAA caused liver fibrosis in rat after 30 d of treatment. CsA alleviates the morphological changes of TAA-induced fibrosis in rat liver. The blood glutamyl oxaloacetic transaminase (GOT)/glutamyl pyruvic transaminase (GPT) in the TAA-injury group is elevated compared to that of the normal rat. Compared with the TAA-injury group, the blood GOT/GPT and TGFbeta1 (by RT-PCR analysis) are reduced in the CsA plus TAA-treated rat. The level of the transforming growth factor receptor I (TGFbeta-R1) in the CsA plus TAA-treated group shows higher than that in the TAA only group, but shows a lower level of the fibroblast growth factor receptor 4 (FGFR4) in the CsA plus TAA-treated group, when using the Western blot analysis. After immunostaining of the frozen section, TGFbeta-R1 and FGFR4 are more concentrated in rat liver after CsA plus TAA injury.


CONCLUSIONS
This result suggests that CsA has an alleviated effect on TAA-induced liver injury by increasing the multidrug resistance P-glycoprotein and could be through the regulation of TGFbeta-R1 and FGFR4.
Fan
Sabrina
S
Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan, China.
Weng
Ching-Feng
CF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D030201:Activin Receptors, Type I / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D016572:Cyclosporine / Q000494:pharmacology*; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D051499:Receptor, Fibroblast Growth Factor, Type 4; D000077293:Receptor, Transforming Growth Factor-beta Type I; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D013853:Thioacetamide
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D017468:Receptors, Fibroblast Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D013853:Thioacetamide; D016572:Cyclosporine; C496373:Fgfr4 protein, rat; D051499:Receptor, Fibroblast Growth Factor, Type 4; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat