Effect of leflunomide on immunological liver injury in mice.
OBJECTIVE
To study the effect of leflunomide on immunological liver injury (ILI) in mice.


METHODS
ILI was induced by tail vein injection of 2.5 mg Bacillus Calmette-Guerin (BCG), and 10 d later with 10 microg lipopolysaccharide (LPS) in 0.2 mL saline (BCG+LPS). The alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) level in plasma and molondiadehyde (MDA), glutathione peroxidase (GSHpx) in liver homogenate were assayed by spectroscopy. The serum content of tumor necrosis factors-alpha (TNF-alpha) was determined by ELISA. Interleukin-1 (IL-1), interleukin-2 (IL-2) and Concanavalin A (ConA)-induced splenocyte proliferation response were determined by methods of (3)H-infiltrated cell proliferation.


RESULTS
Leflunomide (4, 12, 36 mg.kg(-1)) was found to significantly decrease the serum transaminase (ALT, AST) activity and MDA content in liver homogenate, and improve reduced GSHpx level of liver homogenate. Leflunomide (4, 12, 36 mg.kg(-1)) significantly lowered TNF-alpha and NO level in serum, and IL-1 produced by intraperitoneal macrophages(PMphi). Moreover, the decreased IL-2 production and ConA-induced splenocyte proliferation response were further inhibited.


CONCLUSIONS
These findings suggested that leflunomide had significant protective action on ILI in mice.
Yao
Hong-Wei
HW
Institute of Clinical Pharmacology, Anhui Medical University, Heifei 230032, Anhui Province, China.
Li
Jun
J
Jin
Yong
Y
Zhang
Yun-Fang
YF
Li
Chang-Yu
CY
Xu
Shu-Yun
SY
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D007555:Isoxazoles / Q000627:therapeutic use*; D000077339:Leflunomide; D008070:Lipopolysaccharides / Q000276:immunology; D008107:Liver Diseases / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009163:Mycobacterium bovis / Q000276:immunology
D000276:Adjuvants, Immunologic; D007555:Isoxazoles; D008070:Lipopolysaccharides; D000077339:Leflunomide