Combined effects of an antioxidant and caspase inhibitor on the reversal of hepatic fibrosis in rats

被引：21

作者：

Kim, Do Young ^{[1
,2
]}

Chung, Sook In ^{[2
,3
]}

Ro, Simon Weonsang ^{[1
,2
]}

Paik, Yong Han ^{[4
]}

Lee, Jung Il ^{[1
,2
]}

Jung, Man Kil ^{[5
]}

Lee, Min Goo ^{[6
]}

Park, Young Nyun ^{[2
,7
]}

Lee, Kwan Sik ^{[1
,2
]}

Park, Jung Gyu ^{[8
]}

Park, Hee Dong ^{[8
]}

Han, Kwang-Hyub ^{[1
,2
]}

机构：

[1] Yonsei Univ, Coll Med, Dept Internal Med, Seoul 120752, South Korea

[2] Liver Cirrhosis Clin Res Ctr, Seoul, South Korea

[3] Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Seoul 120752, South Korea

[4] Sungkyunkwan Univ, Sch Med, Dept Med, Seoul, South Korea

[5] Yonsei Univ, Coll Med, Dept Chem, Seoul 120752, South Korea

[6] Yonsei Univ, Coll Med, Dept Pharmacol, Seoul 120752, South Korea

[7] Yonsei Univ, Coll Med, Dept Pathol, Seoul 120752, South Korea

[8] LG Life Sci Ltd, Taejon, South Korea

来源：

APOPTOSIS | 2013年 / 18卷 / 12期

关键词：

Hepatic fibrosis; Caspase inhibitor; Antioxidant; Rat; MAGNESIUM LITHOSPERMATE-B; STELLATE CELLS; OXIDATIVE STRESS; APOPTOSIS; MECHANISMS; STEATOSIS; IDN-6556; OXIDASE; IMPACT;

D O I：

10.1007/s10495-013-0896-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

We sought to determine the hepatic fibrosis-reversal effects upon simultaneous administration of lithospermate B (LAB), an anti-oxidant, and nivocasan, a caspase inhibitor, to rats compared with each compound alone. Liver fibrosis was induced in Sprague-Dawley rats by thioacetamide (TAA). Rats were treated with TAA and then given LAB and (or) nivocasan. Fibrotic areas were evaluated quantitatively by computerized morphometry. Apoptosis was assessed using a TUNEL assay, and immunohistochemical staining for malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4HNE) was performed to assess oxidative stress levels. Real-time quantitative PCR was used to quantify expression of fibrosis-related genes. The degree of hepatic fibrosis was significantly reduced in rats treated with LAB and nivocasan compared to either treatment alone (P < 0.001). Treatment with each compound significantly decreased expression of fibrosis-related genes, such as type I collagen alpha 1 (col1 alpha 1), alpha-SMA and TGF-beta 1 (P < 0.05). Co-treatment with LAB and nivocasan further reduced col1 alpha 1 expression compared to treatment with either compound. A TUNEL assay revealed that hepatocyte apoptosis was significantly decreased in the group treated with nivocasan compared to other groups (P < 0.01). Immunohistochemistry showed a decrease in MDA and 4HNE, reflecting amelioration of oxidative stress, when LAB or LAB+nivocasan was administered compared to nivocasan alone (P < 0.01). Nivocasan was found to inhibit caspase-1, -3, -7, -9 and gliotoxin-induced death of rat-derived hepatic stellate cells was inhibited by nivocasan administration without overexpression of alpha-SMA. Conclusions: Co-incidental administration of LAB and nivocasan suppressed oxidative stress and apoptosis, resulting in enhanced reversal of hepatic fibrosis in rat.

引用

页码：1481 / 1491

页数：11

共 34 条

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