Antifibrotic effects of ambrisentan, an endothelin-A receptor antagonist, in a non-alcoholic steatohepatitis mouse model

Table 1 Effects of ambrisentan administration on various parameters in fatty liver shionogi-ob/ob mice

Parameters	Control group (n = 5)	Ambrisentan group (n = 8)	P value
Body weight (g)	47.3 ± 3.6	47.0 ± 4.6	0.27
Liver weight (g)	5.4 ± 1.2	5.1 ± 1.1	0.75
Liver/body weight ratio	0.11 ± 0.02	0.11 ± 0.01	0.68
Visceral fat weight (g)	2.5 ± 0.3	2.7 ± 0.3	0.32
Weekly dietary intake (g)	31.7 ± 9.3	29.4 ± 9.0	0.66
Serum AST (U/L)	143 ± 20	155 ± 43	0.59
Serum ALT (U/L)	120 ± 52	151 ± 65	0.38
Hepatic cholesterol (mg/dL)	24.5 ± 1.56	27.2 ± 2.58	0.06
Hepatic triglyceride (mg/dL)	1152 ± 500	929 ± 210	0.28

AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.

Table 2 Hepatic mRNA expression levels of various genes in the control and ambrisentan groups

mRNA	Control group (n = 5)	Ambrisentan group (n = 8)	P value
Procollagen-1	1.76 ± 0.58	1.06 ± 0.43	0.024
TGF-β1	1.60 ± 0.80	1.14 ± 0.17	0.13
CTGF	1.43 ± 0.49	1.52 ± 0.40	0.36
TIMP-1	2.98 ± 1.58	1.34 ± 0.61	0.02
TNF-α	2.37 ± 2.65	2.37 ± 3.02	1
MCP-1	10.20 ± 10.06	8.14 ± 8.90	0.39
SREBP1c	0.69 ± 0.19	0.80 ± 0.17	0.29
FAS	0.76 ± 0.34	0.87 ± 0.46	0.67
PPAR-α	0.81 ± 0.16	0.98 ± 0.27	0.24
MTP	0.95 ± 0.09	0.99 ± 0.09	0.45
ET-1	1.40 ± 0.57	1.47 ± 0.50	0.82
ECE	1.02 ± 0.13	1.23 ± 0.23	0.09
ETAR	3.74 ± 3.35	2.55 ± 1.56	0.4
ETBR	2.07 ± 0.76	1.87 ± 0.49	0.59

TGF: Transforming growth factor; CTGF: Connective tissue growth factor; TIMP: Tissue inhibitor of metalloproteinase; TNF: Tumor necrosis factor; MCP: Monocyte chemoattractant protein; SREBP: Sterol regulatory element-binding protein; FAS: Fatty acid synthase; PPAR: Peroxisome proliferator-activated receptor; MTP: Microsomal triglyceride transfer protein; ET: Endothelin; ECE: Endothelin-converting enzyme; ETAR: Endothelin type A receptor; ETBR: Endothelin type B receptor.