Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways

Hemorrhagic cystitis is an important complication of cyclophosphamide chemotherapy, and current therapies for the disease are limited. The natural flavonoid luteolin (LUT) has significant anti-inflammatory and antioxidant properties, but its protective effect on cyclophosphamide (CYP)-induced bladde...

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Autores principales:	Hengshuai Zhang, Jiang Zhao, Qudong Lu, Bishao Sun, Xin Liu, Chengfei Yang, Shuai Li, Longkun Li, Shanhong Yi, Zhenxing Yang, Jie Xu
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Other systems of medicine RZ201-999
Acceso en línea:	https://doaj.org/article/3e3dbad581154baf86c0adee2edb37da
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spelling	oai:doaj.org-article:3e3dbad581154baf86c0adee2edb37da2021-11-22T01:11:30ZLuteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways1741-428810.1155/2021/1718709https://doaj.org/article/3e3dbad581154baf86c0adee2edb37da2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/1718709https://doaj.org/toc/1741-4288Hemorrhagic cystitis is an important complication of cyclophosphamide chemotherapy, and current therapies for the disease are limited. The natural flavonoid luteolin (LUT) has significant anti-inflammatory and antioxidant properties, but its protective effect on cyclophosphamide (CYP)-induced bladder toxicity has yet to be evaluated. This study aims to explore the protective effect of LUT on CYP-induced acute cystitis in rats. Female Sprague-Dawley rats were randomly assigned to the control (CON) group, CON + LUT group, CYP group, and CYP + LUT group. A single intraperitoneal injection of CYP was administered to establish an acute hemorrhagic cystitis model. HE staining was performed to detect the degree of bladder tissue damage, and TUNEL staining was performed to count apoptotic cells. Oxidative stress indicators were measured using commercial kits, and bladder surgery was performed to assess urinary function. The levels of inflammatory cytokines, apoptosis-related indicators, TXNIP/NLRP3 pathway, and NF-κB pathway were detected by western blot. We found that LUT treatment reduced bladder bleeding, congestion, and edema caused by CYP. Compared with the CYP + LUT group, the level of apoptosis was more highly expressed in the CYP group. We also found that caspase-3, caspase-8, and Bax were significantly upregulated and Bcl-2 was downregulated after LUT treatment. In addition, LUT inhibited the activation of NF-κB signal pathway in the rat bladder tissue after CYP exposure. LUT treatment can also reduce the NLRP3 inflammasome (NLRP3, ASC, and caspase-1) and TXNIP in the bladder. Finally, LUT can reduce the increase in the urination frequency and maximum urination pressure caused by cystitis. These results indicate that LUT displays effective anti-inflammatory, antioxidant, and antiapoptotic properties in CYP-induced acute hemorrhagic cystitis rats by inhibiting the TXNIP/NLRP3 and NF-κB pathways. LUT may be a potent therapeutic agent for the prevention and treatment of hemorrhagic cystitis.Hengshuai ZhangJiang ZhaoQudong LuBishao SunXin LiuChengfei YangShuai LiLongkun LiShanhong YiZhenxing YangJie XuHindawi LimitedarticleOther systems of medicineRZ201-999ENEvidence-Based Complementary and Alternative Medicine, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Other systems of medicine RZ201-999
spellingShingle	Other systems of medicine RZ201-999 Hengshuai Zhang Jiang Zhao Qudong Lu Bishao Sun Xin Liu Chengfei Yang Shuai Li Longkun Li Shanhong Yi Zhenxing Yang Jie Xu Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways
description	Hemorrhagic cystitis is an important complication of cyclophosphamide chemotherapy, and current therapies for the disease are limited. The natural flavonoid luteolin (LUT) has significant anti-inflammatory and antioxidant properties, but its protective effect on cyclophosphamide (CYP)-induced bladder toxicity has yet to be evaluated. This study aims to explore the protective effect of LUT on CYP-induced acute cystitis in rats. Female Sprague-Dawley rats were randomly assigned to the control (CON) group, CON + LUT group, CYP group, and CYP + LUT group. A single intraperitoneal injection of CYP was administered to establish an acute hemorrhagic cystitis model. HE staining was performed to detect the degree of bladder tissue damage, and TUNEL staining was performed to count apoptotic cells. Oxidative stress indicators were measured using commercial kits, and bladder surgery was performed to assess urinary function. The levels of inflammatory cytokines, apoptosis-related indicators, TXNIP/NLRP3 pathway, and NF-κB pathway were detected by western blot. We found that LUT treatment reduced bladder bleeding, congestion, and edema caused by CYP. Compared with the CYP + LUT group, the level of apoptosis was more highly expressed in the CYP group. We also found that caspase-3, caspase-8, and Bax were significantly upregulated and Bcl-2 was downregulated after LUT treatment. In addition, LUT inhibited the activation of NF-κB signal pathway in the rat bladder tissue after CYP exposure. LUT treatment can also reduce the NLRP3 inflammasome (NLRP3, ASC, and caspase-1) and TXNIP in the bladder. Finally, LUT can reduce the increase in the urination frequency and maximum urination pressure caused by cystitis. These results indicate that LUT displays effective anti-inflammatory, antioxidant, and antiapoptotic properties in CYP-induced acute hemorrhagic cystitis rats by inhibiting the TXNIP/NLRP3 and NF-κB pathways. LUT may be a potent therapeutic agent for the prevention and treatment of hemorrhagic cystitis.
format	article
author	Hengshuai Zhang Jiang Zhao Qudong Lu Bishao Sun Xin Liu Chengfei Yang Shuai Li Longkun Li Shanhong Yi Zhenxing Yang Jie Xu
author_facet	Hengshuai Zhang Jiang Zhao Qudong Lu Bishao Sun Xin Liu Chengfei Yang Shuai Li Longkun Li Shanhong Yi Zhenxing Yang Jie Xu
author_sort	Hengshuai Zhang
title	Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways
title_short	Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways
title_full	Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways
title_fullStr	Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways
title_full_unstemmed	Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways
title_sort	luteolin improves cyclophosphamide-induced cystitis through txnip/nlrp3 and nf-κb pathways
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/3e3dbad581154baf86c0adee2edb37da
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Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways

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