Co-administration of cyclosporine A alleviates thioacetamide-induced liver injury

Abstract

AIM:To investigate the effects of cyclosporine A (CsA) on thioacetamide (TAA)-induced liver injury. METHODS:CsA was co-administrated (7.5 g/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 TGF1 (by RT-PCR analysis) are reduced in the CsA plus TAA-treated rat. The level of the transforming growth factor receptor I (TGF-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, TGF-R1 and FGFR4 are more concentrated in rat liver after CsA plus TAA injury. CONCLUSION: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 TGF-R1 and FGFR4.

Down-regulation of TGFβ1 and leptin ameliorates thioacetamide-induced liver injury in lipopolysaccharide-primed rats

“…30 In the present work, rats treated ten times with TAA (200 mg/kg body weight) suffered liver injury, including high GOT/GPT levels, and collagen 1 and collagen 3 mRNA levels that are consistent with those previously reported. 31 Additionally, the increases in TGFβ1 and leptin mRNA expression in TAA-treated rats caused liver injury, as described in a previous investigation. 28 Exposure to a sublethal dose of LPS renders animals tolerant to a lethal dose of LPS, and protects against the toxicity of some chemicals.…”

“…injection of thioacetamide (TAA, 200 mg/kg body weight, every 3 days for 30 days) as described elsewhere. 31 Animals in the LPS plus TAA group were given one dose of LPS (5 mg/kg body weight, i.p.) at 24 h before TAA was administered.…”

Hypoxia induces the activation of human hepatic stellate cells LX‐2 through TGF‐β signaling pathway

“…The extracellular portion of the protein interacts with fibroblast growth factors (FGF), setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. The expression of FGFR4 was increased in hepatic fibrotic rats induced by thioacetamide [28]. Recently, an agonist role for FGF1 and FGF2 is seen in specifically insult-induced liver matrix deposition and hepatic fibrogenesis and as a potential target for the prevention of hepatic fibrosis by acute CCl 4 exposure [29].…”

N‐methyl‐4‐isoleucine cyclosporine attenuates CCl4‐induced liver fibrosis in rats by interacting with cyclophilin B and D

“…Cyclophilins are the binding proteins of CsA and its derivatives. Cyclophilin (CyP) plays an important role in intracellular signal conduction, antiviral activity, cell regeneration and MPT 13–15 . CyP A exclusively binds with CsA and, has been recently reported to be the target through which CsA exerts its anti‐HCV effect 16 .…”