S-allylcysteine is effective as a chemopreventive agent against porcine serum-induced hepatic fibrosis in rats.

Osaka city medical journal Pub Date : 2009-12-01
Hiroji Shinkawa, Shigekazu Takemura, Yukiko Minamiyama, Shintaro Kodai, Takuma Tsukioka, Mayuko Osada-Oka, Shoji Kubo, Shigeru Okada, Shigefumi Suehiro
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Abstract

Background: Hepatic fibrosis is a chronic progressive disorder with a poor prognosis for which no definitive treatment exists. S-allylcysteine (SAC), an ingredient of aged garlic extract, is known to have antioxidant and hepatoprotective effects. The aim of this study was to investigate the antifibrotic effects of SAC in the liver.

Methods: Hepatic fibrosis was induced in male Wistar rats by porcine serum (PS) intraperitoneal injection. SAC (0.15% of basal diet) or N-acetylcysteine (NAC, 0.45% of basal diet) was orally administered for 12 weeks. Liver damage was assessed by the levels of plasma alanine aminotransferase (ALT), hepatic lipid peroxides (LPO), and hepatic total thiols 12 weeks after first PS injection. Area of fibrosis was examined by Azan-Mallory staining. Hydroxyproline content of liver were assessed as an index of collagen content. Liver was examined for expression of alpha-smooth muscle actin (alpha-SMA) as a marker of hepatic stellate cell (HSC) activation.

Results: There were no significant differences in levels of plasma ALT, hepatic LPO, or hepatic total thiols among the groups. PS significantly increased area of fibrosis and hydroxyproline content in the liver. SAC and NAC each markedly attenuated the development ofhepatic fibrosis. SAC and NAC markedly suppressed the PS-induced increase in alpha-SMA expressions.

Conclusions: Oral administration of SAC reduced PS-induced hepatic fibrosis in rats via inhibition of HSC activation. SAC could provide a new therapeutic strategy for hepatic fibrosis.

s -丙氨酸半胱氨酸是一种有效的化学预防剂,可预防猪血清诱导的大鼠肝纤维化。
背景:肝纤维化是一种慢性进行性疾病,预后不良,尚无明确的治疗方法。s -丙烯基半胱氨酸(SAC)是陈年大蒜提取物的一种成分,已知具有抗氧化和保护肝脏的作用。本研究的目的是探讨SAC在肝脏中的抗纤维化作用。方法:采用猪血清(PS)腹腔注射诱导雄性Wistar大鼠肝纤维化。口服SAC(0.15%基础饲粮)或n -乙酰半胱氨酸(NAC, 0.45%基础饲粮)12周。第一次注射PS后12周,通过血浆丙氨酸转氨酶(ALT)、肝脂质过氧化物(LPO)和肝总硫醇水平评估肝损伤。Azan-Mallory染色检查纤维化面积。肝脏羟脯氨酸含量作为胶原蛋白含量的指标。检测肝脏α -平滑肌肌动蛋白(α - sma)的表达,作为肝星状细胞(HSC)活化的标志。结果:两组间血浆ALT、肝LPO、肝总硫醇水平无显著性差异。PS显著增加肝脏纤维化面积和羟脯氨酸含量。SAC和NAC均能显著减轻肝纤维化的发生。SAC和NAC显著抑制ps诱导的α - sma表达增加。结论:口服SAC可通过抑制HSC活化来减轻ps诱导的大鼠肝纤维化。SAC可为肝纤维化提供新的治疗策略。
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