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15-Deoxy-Δ12,14-prostaglandin J2 alleviates hepatic ischemia-reperfusion injury in mice via inducing antioxidant response and inhibiting apoptosis and autophagy.
Acta Pharmacol Sin. 2017 May; 38(5):672-687.AP

Abstract

Hepatic ischemia-reperfusion (I/R) injury is a common clinical impairment that occurs in many circumstances and leads to poor prognosis. Both apoptosis and autophagy have been shown to contribute to cell death in hepatic I/R injury. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is one of the best-studied anti-inflammatory prostaglandins, which has been verified to exert anti-inflammatory and cell-protective functions in various types of cells and animal models. In this study we explored the effects of 15d-PGJ2 on both apoptosis and autophagy in mouse hepatic I/R injury and its possible mechanisms. A model of segmental (70%) hepatic warm ischemia was established in Balb/c mice, and the pathological changes in serum and liver tissues were detected at 6, 12, and 24 h post-surgery, while 15d-PGJ2 (2.5, 7.5, 15 μg, iv) was administered 30 min prior the surgery. Pretreatment with 15d-PGJ2 (7.5, 15 μg) significantly ameliorated I/R-induced hepatic injury evidenced by dose-dependent reduction of serum ALT and AST levels as well as alleviated tissue damages. 15d-PGJ2 pretreatment significantly decreased the serum TNF-α and IL-1β levels and the hepatic expression of F4/80, a major biomarker of macrophages. 15d-PGJ2 pretreatment upregulated the Bcl-2/Bax ratio, thus reducing the number of apoptotic cells in the livers. 15d-PGJ2 pretreatment considerably suppressed the expression of Beclin-1 and LC3, thus decreasing the number of autophagosomes in the livers. Furthermore, 15d-PGJ2 pretreatment activated Nrf2 and inhibited a ROS/HIF1α/BNIP3 pathway in the livers. Pretreatment with the PPARγ receptor blocker GW9662 (2 μg, ip) partly reversed the protective effects of 15d-PGJ2 on hepatic I/R injury. In conclusion, our results confirm the protective effect of 15d-PGJ2 on hepatic I/R injury, an effect that may rely on a reduction in the activation of Kupffer cells and on activation of the Nrf2 pathway, which lead to inhibition of ROS generation, apoptosis, and autophagy.

Authors+Show Affiliations

Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28216619

Citation

Chen, Kan, et al. "15-Deoxy-Δ12,14-prostaglandin J2 Alleviates Hepatic Ischemia-reperfusion Injury in Mice Via Inducing Antioxidant Response and Inhibiting Apoptosis and Autophagy." Acta Pharmacologica Sinica, vol. 38, no. 5, 2017, pp. 672-687.
Chen K, Li JJ, Li SN, et al. 15-Deoxy-Δ12,14-prostaglandin J2 alleviates hepatic ischemia-reperfusion injury in mice via inducing antioxidant response and inhibiting apoptosis and autophagy. Acta Pharmacol Sin. 2017;38(5):672-687.
Chen, K., Li, J. J., Li, S. N., Feng, J., Liu, T., Wang, F., Dai, W. Q., Xia, Y. J., Lu, J., Zhou, Y. Q., & Guo, C. Y. (2017). 15-Deoxy-Δ12,14-prostaglandin J2 alleviates hepatic ischemia-reperfusion injury in mice via inducing antioxidant response and inhibiting apoptosis and autophagy. Acta Pharmacologica Sinica, 38(5), 672-687. https://doi.org/10.1038/aps.2016.108
Chen K, et al. 15-Deoxy-Δ12,14-prostaglandin J2 Alleviates Hepatic Ischemia-reperfusion Injury in Mice Via Inducing Antioxidant Response and Inhibiting Apoptosis and Autophagy. Acta Pharmacol Sin. 2017;38(5):672-687. PubMed PMID: 28216619.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 15-Deoxy-Δ12,14-prostaglandin J2 alleviates hepatic ischemia-reperfusion injury in mice via inducing antioxidant response and inhibiting apoptosis and autophagy. AU - Chen,Kan, AU - Li,Jing-Jing, AU - Li,Sai-Nan, AU - Feng,Jiao, AU - Liu,Tong, AU - Wang,Fan, AU - Dai,Wei-Qi, AU - Xia,Yu-Jing, AU - Lu,Jie, AU - Zhou,Ying-Qun, AU - Guo,Chuan-Yong, Y1 - 2017/02/20/ PY - 2015/11/15/received PY - 2016/08/25/accepted PY - 2017/2/22/pubmed PY - 2018/4/18/medline PY - 2017/2/21/entrez SP - 672 EP - 687 JF - Acta pharmacologica Sinica JO - Acta Pharmacol. Sin. VL - 38 IS - 5 N2 - Hepatic ischemia-reperfusion (I/R) injury is a common clinical impairment that occurs in many circumstances and leads to poor prognosis. Both apoptosis and autophagy have been shown to contribute to cell death in hepatic I/R injury. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is one of the best-studied anti-inflammatory prostaglandins, which has been verified to exert anti-inflammatory and cell-protective functions in various types of cells and animal models. In this study we explored the effects of 15d-PGJ2 on both apoptosis and autophagy in mouse hepatic I/R injury and its possible mechanisms. A model of segmental (70%) hepatic warm ischemia was established in Balb/c mice, and the pathological changes in serum and liver tissues were detected at 6, 12, and 24 h post-surgery, while 15d-PGJ2 (2.5, 7.5, 15 μg, iv) was administered 30 min prior the surgery. Pretreatment with 15d-PGJ2 (7.5, 15 μg) significantly ameliorated I/R-induced hepatic injury evidenced by dose-dependent reduction of serum ALT and AST levels as well as alleviated tissue damages. 15d-PGJ2 pretreatment significantly decreased the serum TNF-α and IL-1β levels and the hepatic expression of F4/80, a major biomarker of macrophages. 15d-PGJ2 pretreatment upregulated the Bcl-2/Bax ratio, thus reducing the number of apoptotic cells in the livers. 15d-PGJ2 pretreatment considerably suppressed the expression of Beclin-1 and LC3, thus decreasing the number of autophagosomes in the livers. Furthermore, 15d-PGJ2 pretreatment activated Nrf2 and inhibited a ROS/HIF1α/BNIP3 pathway in the livers. Pretreatment with the PPARγ receptor blocker GW9662 (2 μg, ip) partly reversed the protective effects of 15d-PGJ2 on hepatic I/R injury. In conclusion, our results confirm the protective effect of 15d-PGJ2 on hepatic I/R injury, an effect that may rely on a reduction in the activation of Kupffer cells and on activation of the Nrf2 pathway, which lead to inhibition of ROS generation, apoptosis, and autophagy. SN - 1745-7254 UR - https://www.unboundmedicine.com/medline/citation/28216619/15_Deoxy_Δ1214_prostaglandin_J2_alleviates_hepatic_ischemia_reperfusion_injury_in_mice_via_inducing_antioxidant_response_and_inhibiting_apoptosis_and_autophagy_ L2 - http://dx.doi.org/10.1038/aps.2016.108 DB - PRIME DP - Unbound Medicine ER -