Expression of MMP-9 in hepatic sinusoidal obstruction syndrome induced by Gynura segetum

Abstract

Background and objective: Hepatic sinusoidal obstruction syndrome (HSOS) is characterized by painful hepatomegaly, ascites, increased body weight, and jaundice. Gynura segetum (Compositae), a plant widely used in Chinese traditional medicine, often leads to the development of HSOS. However, the mechanism is unclear. The aim was to study the role of matrix metalloproteinase-9 (MMP-9) in the onset of HSOS induced by Gynura segetum. Methods: Twenty-five male Sprague-Dawley rats were randomly divided into two groups. Twenty were exposed to 600 mg/kg daily Gynura segetum extract solution for three weeks; five control rats were exposed to tap water alone. Liver sections were evaluated by light microscopy with a modified scoring system. Routine transmission electron microscopy (TEM) methods were used to evaluate the ultrastructual features of fixed liver tissue, and blood samples were collected to determine liver enzyme concentrations. MMP-9 expression was assessed by both immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA) methods. Results: A stable and reproducible rat model of HSOS was achieved by long-term exposure to Gynura segetum extract. The treated rats presented clinical symptoms and the histopathological manifestation of HSOS, including abnormal liver enzyme concentrations (alanine aminotransferase (ALT): (84.8±13.62) vs. (167.0±72.63) U/L, P<0.05; aspartate aminotransferase (AST): (27.6±6.31) vs. (232.8±108.58) U/L, P<0.05). Hematoxylin and eosin (H&E) staining and TEM together revealed deposition of red blood cells, the damage and destruction of hepatic sinusoidal endothelial cells, collapse of hepatic sinusoids, hemorrhage of subendothelial cells, atrophy and destruction of hepatocytes, etc. Compared with controls, the expression of MMP-9 in the blood sample, the lung and liver tissues of HSOS rats was increased. Conclusions: MMP-9 may have an important role in early pathological changes of HSOS, and thus the onset of the disease.

Pyrrolizidine Alkaloids: Biosynthesis, Biological Activities and Occurrence in Crop Plants

“…It has been shown to have anti-angiogenic [263] as well as antioxidative and anti-inflammatory properties [264]. Its medicinal use is risky though as there have been several reports of hepatic veno-occlusive disease linked to the consumption of G. segetum [265,266,267,268]. Liang and Roeder were the first to characterize senecionine from G. segetum [269].…”

A Critical Analysis of Experimental Animal Models of Sinusoidal Obstruction Syndrome

“…53 Although pre-HSCT conditioning therapy is the most common reason for developing SOS in the Western Hemisphere, in China, ingestion of PA-containing plants, such as G. segetum, frequently causes SOS in humans as well. 54 As a PA, G. segetum acts similarly to MCT, specifically by increasing MMP-9 levels, as shown in a study by Yu et al 43 (Table 5). More recently, a study by Qiu et al (2018) identified 18 metabolites, commonly found in urine and plasma, that can serve as potential diagnostic markers for G. segetuminduced hepatotoxicity.…”

Bone marrow sinusoidal endothelium as a facilitator/regulator of cell egress from the bone marrow

“…(MMP-9), for example, has been proposed to play a key role to regulate normal HC egression from BM (Lane et al, 2000). While production of MMP-9 by hepatic SECs has been reported (Yu et al, 2013), further studies will reveal whether BM SECs also produce MMP-9 and hence have any roles in egress of cells from BM. Taken together, BM SECs appear to be involved in regulation of cell egress from BM by providing adhesion molecules, chemokines, and possibly MMP-9 to the egressing cells.…”