Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Isolinderalactone Resistance to the Liver Injury Induced by Oxaliplatin in Rats Through Inhibiting IL-6/STAT3 Signal Pathway

Author(s): Rongwei Lin, Yang Zhou, Chao Hu, Hongqing Yao and Wangxun Jin*

Volume 23, Issue 12, 2023

Published on: 20 April, 2023

Page: [1415 - 1420] Pages: 6

DOI: 10.2174/1871520623666230112165440

Price: $65

Abstract

Background: Oxaliplatin (OXA) is easy to cause sinusoidal obstruction syndrome (SOS), leading to liver injury. Isolinderalactone (ILL), one of the main components of Lindera aggregate, has been reported to have a protecting effect on the liver. However, it is unclear whether ILL has a therapeutic effect on liver injury caused by OXA. This study aims to determine the effect of ILL on the prevention and treatment of OXA-induced liver injury and to provide a basis for the chemotherapy of gastrointestinal tumors.

Methods: Intraperitoneal injection of folinic acid, 5-fluorouracil, and OXA was administered on the SOS rat model for 7 weeks. The indexes of liver function were measured by biochemical kit. The ratio of liver weight to body weight was calculated. The pathological analysis of the liver was scored with the SOS scoring standard, fibrosis was evaluated with a four-point scale. The expression of inflammation factors was detected by Real-Time PCR, and the related indexes of IL-6/STAT3 were examined by Western blot analysis.

Results: ILL down-regulated the portal vein pressure and alleviated the abnormal liver function of SOS rats and improved the liver lesions. ILL inhibited the SOS by inhibiting IL-6/STAT3.

Conclusion: ILL resistance to liver injury through inhibiting IL-6/STAT3 signal pathway.

Keywords: ILL, liver injury, OXA, SOS, IL-6/STAT3, isolinderalactone.

Graphical Abstract
[1]
Fritsch, R.; Hoeppner, J. Oxaliplatin in perioperative chemotherapy for gastric and gastroesophageal junction (GEJ) adenocarcinoma. Expert Rev. Gastroenterol. Hepatol., 2019, 13(4), 285-291.
[http://dx.doi.org/10.1080/17474124.2019.1573143] [PMID: 30791774]
[2]
Li, Y.; Sun, Z.; Cui, Y.; Zhang, H.; Zhang, S.; Wang, X.; Liu, S.; Gao, Q. Oxaliplatin derived monofunctional triazole-containing platinum(II) complex counteracts oxaliplatin-induced drug resistance in colorectal cancer. Bioorg. Chem., 2021, 107, 104636.
[http://dx.doi.org/10.1016/j.bioorg.2021.104636] [PMID: 33465670]
[3]
Zhu, C.; Ren, X.; Liu, D.; Zhang, C. Oxaliplatin-induced hepatic sinusoidal obstruction syndrome. Toxicology, 2021, 460, 152882.
[http://dx.doi.org/10.1016/j.tox.2021.152882] [PMID: 34352347]
[4]
Liu, L.; Zhang, W.; Zhuge, Y.Z. Review on diagnostic criteria of hepatic sinusoidal obstruction syndrome. Zhonghua Gan Zang Bing Za Zhi, 2020, 28(12), 1064-1068.
[PMID: 34865358]
[5]
Miyamoto, T.; Domoto, R.; Sekiguchi, F.; Kamaguchi, R.; Nishimura, R.; Matsuno, M.; Tsubota, M.; Fujitani, M.; Hatanaka, S.; Koizumi, Y.; Wang, D.; Nishibori, M.; Kawabata, A. Development of hepatic impairment aggravates chemotherapy-induced peripheral neuropathy following oxaliplatin treatment: Evidence from clinical and preclinical studies. J. Pharmacol. Sci., 2022, 148(3), 315-325.
[http://dx.doi.org/10.1016/j.jphs.2022.01.006] [PMID: 35177211]
[6]
Kuo, P.C.; Wu, Y.H.; Hung, H.Y.; Lam, S.H.; Ma, G.H.; Kuo, L.M.; Hwang, T.L.; Kuo, D.H.; Wu, T.S. Anti-inflammatory principles from Lindera aggregata. Bioorg. Med. Chem. Lett., 2020, 30(13), 127224.
[http://dx.doi.org/10.1016/j.bmcl.2020.127224] [PMID: 32359855]
[7]
Yang, J.J.; Chen, Y.; Guo, M.L.; Chou, G.X. Chemical constituents from the roots of Lindera aggregata and their biological activities. J. Nat. Med., 2020, 74(2), 441-447.
[http://dx.doi.org/10.1007/s11418-019-01385-6] [PMID: 31912311]
[8]
Chen, Y.; Li, R.; Hu, N.; Yu, C.; Song, H.; Li, Y.; Dai, Y.; Guo, Z.; Li, M.; Zheng, Y.; Guo, Z.; Qi, Y. Baihe Wuyao decoction ameliorates CCl4-induced chronic liver injury and liver fibrosis in mice through blocking TGF-β1/Smad2/3 signaling, anti-inflammation and anti-oxidation effects. J. Ethnopharmacol., 2020, 263, 113227.
[http://dx.doi.org/10.1016/j.jep.2020.113227] [PMID: 32783983]
[9]
Wang, J.W.; Chen, X.Y.; Hu, P.Y.; Tan, M.M.; Tang, X.G.; Huang, M.C.; Lou, Z.H. Effects of Linderae radix extracts on a rat model of alcoholic liver injury. Exp. Ther. Med., 2016, 11(6), 2185-2192.
[http://dx.doi.org/10.3892/etm.2016.3244] [PMID: 27313665]
[10]
Yen, M.C.; Shih, Y.C.; Hsu, Y.L.; Lin, E.S.; Lin, Y.S.; Tsai, E.M.; Ho, Y.A.W.E.N.; Hou, M.F.; Kuo, P.O.L.I.N. Isolinderalactone enhances the inhibition of SOCS3 on STAT3 activity by decreasing miR-30c in breast cancer. Oncol. Rep., 2016, 35(3), 1356-1364.
[http://dx.doi.org/10.3892/or.2015.4503] [PMID: 26707189]
[11]
Kwak, A.W.; Park, J.W.; Lee, S.O.; Lee, J.Y.; Seo, J.; Yoon, G.; Lee, M.H.; Choi, J.S.; Shim, J.H. Isolinderalactone sensitizes oxaliplatin-resistance colorectal cancer cells through JNK/p38 MAPK signaling pathways. Phytomedicine, 2022, 105, 154383.
[http://dx.doi.org/10.1016/j.phymed.2022.154383] [PMID: 35987016]
[12]
Rajina, S.; Kim, W.J.; Shim, J.H.; Chun, K.S.; Joo, S.H.; Shin, H.K.; Lee, S.Y.; Choi, J.S. Isolinderalactone induces cell death via mitochondrial superoxide- and STAT3-mediated pathways in human ovarian cancer cells. Int. J. Mol. Sci., 2020, 21(20), 7530.
[http://dx.doi.org/10.3390/ijms21207530] [PMID: 33066004]
[13]
Robinson, S.M.; Mann, J.; Vasilaki, A.; Mathers, J.; Burt, A.D.; Oakley, F.; White, S.A.; Mann, D.A. Pathogenesis of FOLFOX induced sinusoidal obstruction syndrome in a murine chemotherapy model. J. Hepatol., 2013, 59(2), 318-326.
[http://dx.doi.org/10.1016/j.jhep.2013.04.014] [PMID: 23624001]
[14]
Zhao, J.; Liu, X.; Chen, Y.; Zhang, L.S.; Zhang, Y.R.; Ji, D.R.; Liu, S.M.; Jia, M.Z.; Zhu, Y.H.; Qi, Y.F.; Lu, F.M.; Yu, Y.R. STAT3 promotes schistosome-induced liver injury by inflammation, oxidative stress, proliferation, and apoptosis signal pathway. Infect. Immun., 2021, 89(3), e00309-20.
[http://dx.doi.org/10.1128/IAI.00309-20] [PMID: 33257536]
[15]
Park, S.H.; Lee, S.S.; Sung, J.Y.; Na, K.; Kim, H.J.; Kim, S.Y.; Park, B.J.; Byun, J.H. Noninvasive assessment of hepatic sinusoidal obstructive syndrome using acoustic radiation force impulse elastography imaging: A proof-of-concept study in rat models. Eur. Radiol., 2018, 28(5), 2096-2106.
[http://dx.doi.org/10.1007/s00330-017-5179-z] [PMID: 29218616]
[16]
Corbacioglu, S.; Jabbour, E.J.; Mohty, M. Risk factors for development of and progression of hepatic veno-occlusive disease/sinusoidal obstruction syndrome. Biol. Blood Marrow Transplant., 2019, 25(7), 1271-1280.
[http://dx.doi.org/10.1016/j.bbmt.2019.02.018] [PMID: 30797942]
[17]
Slade, J.H.; Alattar, M.L.; Fogelman, D.R.; Overman, M.J.; Agarwal, A.; Maru, D.M.; Coulson, R.L.; Charnsangavej, C.; Vauthey, J.N.; Wolff, R.A.; Kopetz, S. Portal hypertension associated with oxaliplatin administration: Clinical manifestations of hepatic sinusoidal injury. Clin. Colorectal Cancer, 2009, 8(4), 225-230.
[http://dx.doi.org/10.3816/CCC.2009.n.038] [PMID: 19822514]
[18]
Overman, M.J.; Maru, D.M.; Charnsangavej, C.; Loyer, E.M.; Wang, H.; Pathak, P.; Eng, C.; Hoff, P.M.; Vauthey, J.N.; Wolff, R.A.; Kopetz, S. Oxaliplatin-mediated increase in spleen size as a biomarker for the development of hepatic sinusoidal injury. J. Clin. Oncol., 2010, 28(15), 2549-2555.
[http://dx.doi.org/10.1200/JCO.2009.27.5701] [PMID: 20406923]
[19]
Lu, Y.; Lin, Y.; Huang, X.; Wu, S.; Wei, J.; Yang, C. Oxaliplatin aggravates hepatic oxidative stress, inflammation and fibrosis in a non alcoholic fatty liver disease mouse model. Int. J. Mol. Med., 2019, 43(6), 2398-2408.
[http://dx.doi.org/10.3892/ijmm.2019.4154] [PMID: 30942432]
[20]
Ribero, D.; Wang, H.; Donadon, M.; Zorzi, D.; Thomas, M.B.; Eng, C.; Chang, D.Z.; Curley, S.A.; Abdalla, E.K.; Ellis, L.M.; Vauthey, J.N. Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer, 2007, 110(12), 2761-2767.
[http://dx.doi.org/10.1002/cncr.23099] [PMID: 17960603]
[21]
Overman, M.J.; Ferrarotto, R.; Raghav, K.; George, B.; Qiao, W.; Machado, K.K.; Saltz, L.B.; Mazard, T.; Vauthey, J.N.; Hoff, P.M.; Hobbs, B.; Loyer, E.M.; Kopetz, S. The addition of bevacizumab to oxaliplatin-based chemotherapy: Impact upon hepatic sinusoidal injury and thrombocytopenia. J. Natl. Cancer Inst., 2018, 110(8), 888-894.
[http://dx.doi.org/10.1093/jnci/djx288] [PMID: 29346573]
[22]
Zou, X.; Wang, Y.; Peng, C.; Wang, B.; Niu, Z.; Li, Z.; Niu, J. Magnesium isoglycyrrhizinate has hepatoprotective effects in an oxaliplatin induced model of liver injury. Int. J. Mol. Med., 2018, 42(4), 2020-2030.
[http://dx.doi.org/10.3892/ijmm.2018.3787] [PMID: 30066834]
[23]
Lu, Y.; Wu, S.; Xiang, B.; Li, L.; Lin, Y. Curcumin attenuates oxaliplatin-induced liver injury and oxidative stress by activating the Nrf2 pathway. Drug Des. Devel. Ther., 2020, 14, 73-85.
[http://dx.doi.org/10.2147/DDDT.S224318] [PMID: 32021093]
[24]
Gan, L.S.; Zheng, Y.L.; Mo, J.X.; Liu, X.; Li, X.H.; Zhou, C.X. Sesquiterpene lactones from the root tubers of Lindera aggregata. J. Nat. Prod., 2009, 72(8), 1497-1501.
[http://dx.doi.org/10.1021/np900354q] [PMID: 19639966]
[25]
Chang, W.; Lin, E.S.; Tsai, M.J.; Huang, M.S.; Kuo, P.L. Isolinderalactone inhibits proliferation of A549 human non-small cell lung cancer cells by arresting the cell cycle at the G0/G1 phase and inducing a Fas receptor and soluble Fas ligand-mediated apoptotic pathway. Mol. Med. Rep., 2014, 9(5), 1653-1659.
[http://dx.doi.org/10.3892/mmr.2014.2015] [PMID: 24604009]
[26]
Deng, Y.; Li, Y. Linderalactone inhibits human lung cancer growth by modulating the expression of apoptosis-related proteins, G2/M cell cycle arrest and inhibition of JAK/STAT signalling pathway. J. BUON, 2019, 24(2), 566-571.
[PMID: 31128007]
[27]
Chuang, C.H.; Wang, L.Y.; Wong, Y.; Lin, E.S. Anti-metastatic effects of isolinderalactone via the inhibition of MMP-2 and up regulation of NM23-H1 expression in human lung cancer A549 cells. Oncol. Lett., 2018, 15(4), 4690-4696.
[http://dx.doi.org/10.3892/ol.2018.7862] [PMID: 29541242]
[28]
Hwang, J.Y.; Park, J.H.; Kim, M.J.; Kim, W.J.; Ha, K.T.; Choi, B.T.; Lee, S.Y.; Shin, H.K. Isolinderalactone regulates the BCL-2/caspase-3/PARP pathway and suppresses tumor growth in a human glioblastoma multiforme xenograft mouse model. Cancer Lett., 2019, 443, 25-33.
[http://dx.doi.org/10.1016/j.canlet.2018.11.027] [PMID: 30503550]
[29]
Park, J.H.; Kim, M.J.; Kim, W.J.; Kwon, K.D.; Ha, K.T.; Choi, B.T.; Lee, S.Y.; Shin, H.K. Isolinderalactone suppresses human glioblastoma growth and angiogenic activity in 3D microfluidic chip and in vivo mouse models. Cancer Lett., 2020, 478, 71-81.
[http://dx.doi.org/10.1016/j.canlet.2020.03.009] [PMID: 32173479]
[30]
Santoro, V.; Jia, R.; Thompson, H.; Nijhuis, A.; Jeffery, R.; Kiakos, K.; Silver, A.R.; Hartley, J.A.; Hochhauser, D. Role of reactive oxygen species in the abrogation of oxaliplatin activity by cetuximab in colorectal cancer. J. Natl. Cancer Inst., 2015, 108(6), djv394.
[http://dx.doi.org/10.1093/jnci/djv394] [PMID: 26719345]
[31]
Tajima, H.; Ohta, T.; Miyashita, T.; Nakanuma, S.; Matoba, M.; Miyata, T.; Sakai, S.; Okamoto, K.; Makino, I.; Kinoshita, J.; Hayashi, H.; Nakamura, K.; Oyama, K.; Inokuchi, M.; Nakagawara, H.; Takamura, H.; Kitagawa, H.; Fushida, S.; Ikeda, H. Oxaliplatin-based chemotherapy induces extravasated platelet aggregation in the liver. Mol. Clin. Oncol., 2015, 3(3), 555-558.
[http://dx.doi.org/10.3892/mco.2015.512] [PMID: 26137266]
[32]
Rubbia-Brandt, L.; Audard, V.; Sartoretti, P.; Roth, A.D.; Brezault, C.; Le Charpentier, M.; Dousset, B.; Morel, P.; Soubrane, O.; Chaussade, S.; Mentha, G.; Terris, B. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann. Oncol., 2004, 15(3), 460-466.
[http://dx.doi.org/10.1093/annonc/mdh095] [PMID: 14998849]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy