Effects of sub-chronic exposure to atmospheric PM2.5 on fibrosis, inflammation, endoplasmic reticulum stress and apoptosis in the livers of rats,Toxicology Research

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Effects of sub-chronic exposure to atmospheric PM2.5 on fibrosis, inflammation, endoplasmic reticulum stress and apoptosis in the livers of rats
Toxicology Research ( IF 2.1 ) Pub Date : 2018-01-10 00:00:00 , DOI: 10.1039/c7tx00262a
Ruijin Li _{1,

2,

3,

4} , Mei Zhang _{1,

2,

3,

4} , Ying Wang _{1,

2,

3,

4} , Ken Kin Lam Yung _{1,

2,

3,

4,

5} , Ruijun Su _{1,

2,

3,

4} , Zhuoyu Li _{1,

2,

3,

4} , Liping Zhao _{3,

4,

6} , Chuan Dong _{1,

2,

3,

4} , Zongwei Cai _{5,

7,

8,

9}

Affiliation

Epidemiological studies have revealed that exposure to PM_2.5 is linked to liver cancer. However, the hepatic toxicity and relevant molecular mechanisms of PM_2.5 have not yet been fully described. Herein, we report on our investigation of the fibrosis, inflammation, endoplasmic reticulum (ER) stress and apoptosis in the livers of rats, caused by exposure to PM_2.5 during summer and winter in Taiyuan, China. Male SD rats were sub-chronically exposed to PM_2.5 (in summer: 0.2, 0.6, 1.5 mg per kg of b.w.; in winter: 0.3, 1.5, 2.7 mg per kg of b.w.) via intratracheal instillation once every 3 days for 60 days. The results showed that exposure to high dosages of PM_2.5 caused the following: (1) hepatic histopathological changes and liver function decline through elevating the activities of AST, ALT, CYP450 and GST; (2) triggered liver fibrosis, in which TGF-β1, Col I, Col III, and MMP13 mRNA and protein expression were significantly upregulated, and enhanced inflammation with the overexpression of TNF-α, IL-6 and HO-1 versus the control; (3) induced liver ER stress and cell apoptosis via activating the GRP78/ATF6/CHOP/TRB3/caspase 12 pathway. The data also indicated that the liver injury induced by winter PM_2.5 in Taiyuan was more serious compared to that induced by summer PM_2.5. This work provides new insight into the mechanisms of PM_2.5-induced liver injury, and aids the understanding of the underlying mechanisms by which PM_2.5 might affect liver diseases.

更新日期：2018-01-10

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