Pioglitazone Ameliorates Acute Endotoxemia-Induced Acute on Chronic Renal Dysfunction in Cirrhotic Ascitic Rats

Endotoxemia-activated tumor necrosis factor (TNFα)/nuclear factor kappa B (NFκB) signals result in acute on chronic inflammation-driven renal dysfunction in advanced cirrhosis. Systemic activation of peroxisome proliferator-activated receptor gamma (PPARγ) with pioglitazone can suppress inflammation...

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Autores principales:	Szu-Yu Liu, Chia-Chang Huang, Shiang-Fen Huang, Tsai-Ling Liao, Nai-Rong Kuo, Ying-Ying Yang, Tzu-Hao Li, Chih-Wei Liu, Ming-Chih Hou, Han-Chieh Lin
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	endotoxemia lipopolysaccharide pioglitazone cirrhosis PPARγ TNFα Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/103438a3d81240c499a61e067294950a
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spelling	oai:doaj.org-article:103438a3d81240c499a61e067294950a2021-11-25T17:10:48ZPioglitazone Ameliorates Acute Endotoxemia-Induced Acute on Chronic Renal Dysfunction in Cirrhotic Ascitic Rats10.3390/cells101130442073-4409https://doaj.org/article/103438a3d81240c499a61e067294950a2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3044https://doaj.org/toc/2073-4409Endotoxemia-activated tumor necrosis factor (TNFα)/nuclear factor kappa B (NFκB) signals result in acute on chronic inflammation-driven renal dysfunction in advanced cirrhosis. Systemic activation of peroxisome proliferator-activated receptor gamma (PPARγ) with pioglitazone can suppress inflammation-related splanchnic and pulmonary dysfunction in cirrhosis. This study explored the mechanism and effects of pioglitazone treatment on the abovementioned renal dysfunction in cirrhotic rats. Cirrhotic ascitic rats were induced with renal dysfunction by bile duct ligation (BDL). Then, 2 weeks of pioglitazone treatment (Pio, PPAR gamma agonist, 12 mg/kg/day, using the azert osmotic pump) was administered from the 6th week after BDL. Additionally, acute lipopolysaccharide (LPS, Escherichia coli 0111:B4; Sigma, 0.1 mg/kg b.w, i.p. dissolved in NaCl 0.9%) was used to induce acute renal dysfunction. Subsequently, various circulating, renal arterial and renal tissue pathogenic markers were measured. Cirrhotic BDL rats are characterized by decreased mean arterial pressure, increased cardiac output and portal venous pressure, reduced renal arterial blood flow (RABF), increased renal vascular resistance (RVR), increased relative renal weight/hydroxyproline, downregulated renal PPARγ expression, upregulated renal inflammatory markers (TNFα, NFκB, IL-6, MCP-1), increased adhesion molecules (VCAM-1 and ICAM-1), increased renal macrophages (M1, CD68), and progressive renal dysfunction (increasing serum and urinary levels of renal injury markers (lipocalin-2 and IL-18)). In particular, acute LPS administration induces acute on chronic renal dysfunction (increasing serum BUN/creatinine, increasing RVR and decreasing RABF) by increased TNFα-NFκB-mediated renal inflammatory markers as well as renal M1 macrophage infiltration. In comparison with the BDL+LPS group, chronic pioglitazone pre-treatment prevented LPS-induced renal pathogenic changes in the BDL-Pio+LPS group. Activation of systemic, renal vessel and renal tissue levels of PPARγ by chronic pioglitazone treatment has beneficial effects on the endotoxemia-related TNFα/NFκB-mediated acute and chronic renal inflammation in cirrhosis. This study revealed that normalization of renal and renal arterial levels of PPARγ effectively prevented LPS-induced acute and chronic renal dysfunction in cirrhotic ascitic rats.Szu-Yu LiuChia-Chang HuangShiang-Fen HuangTsai-Ling LiaoNai-Rong KuoYing-Ying YangTzu-Hao LiChih-Wei LiuMing-Chih HouHan-Chieh LinMDPI AGarticleendotoxemialipopolysaccharidepioglitazonecirrhosisPPARγTNFαBiology (General)QH301-705.5ENCells, Vol 10, Iss 3044, p 3044 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	endotoxemia lipopolysaccharide pioglitazone cirrhosis PPARγ TNFα Biology (General) QH301-705.5
spellingShingle	endotoxemia lipopolysaccharide pioglitazone cirrhosis PPARγ TNFα Biology (General) QH301-705.5 Szu-Yu Liu Chia-Chang Huang Shiang-Fen Huang Tsai-Ling Liao Nai-Rong Kuo Ying-Ying Yang Tzu-Hao Li Chih-Wei Liu Ming-Chih Hou Han-Chieh Lin Pioglitazone Ameliorates Acute Endotoxemia-Induced Acute on Chronic Renal Dysfunction in Cirrhotic Ascitic Rats
description	Endotoxemia-activated tumor necrosis factor (TNFα)/nuclear factor kappa B (NFκB) signals result in acute on chronic inflammation-driven renal dysfunction in advanced cirrhosis. Systemic activation of peroxisome proliferator-activated receptor gamma (PPARγ) with pioglitazone can suppress inflammation-related splanchnic and pulmonary dysfunction in cirrhosis. This study explored the mechanism and effects of pioglitazone treatment on the abovementioned renal dysfunction in cirrhotic rats. Cirrhotic ascitic rats were induced with renal dysfunction by bile duct ligation (BDL). Then, 2 weeks of pioglitazone treatment (Pio, PPAR gamma agonist, 12 mg/kg/day, using the azert osmotic pump) was administered from the 6th week after BDL. Additionally, acute lipopolysaccharide (LPS, Escherichia coli 0111:B4; Sigma, 0.1 mg/kg b.w, i.p. dissolved in NaCl 0.9%) was used to induce acute renal dysfunction. Subsequently, various circulating, renal arterial and renal tissue pathogenic markers were measured. Cirrhotic BDL rats are characterized by decreased mean arterial pressure, increased cardiac output and portal venous pressure, reduced renal arterial blood flow (RABF), increased renal vascular resistance (RVR), increased relative renal weight/hydroxyproline, downregulated renal PPARγ expression, upregulated renal inflammatory markers (TNFα, NFκB, IL-6, MCP-1), increased adhesion molecules (VCAM-1 and ICAM-1), increased renal macrophages (M1, CD68), and progressive renal dysfunction (increasing serum and urinary levels of renal injury markers (lipocalin-2 and IL-18)). In particular, acute LPS administration induces acute on chronic renal dysfunction (increasing serum BUN/creatinine, increasing RVR and decreasing RABF) by increased TNFα-NFκB-mediated renal inflammatory markers as well as renal M1 macrophage infiltration. In comparison with the BDL+LPS group, chronic pioglitazone pre-treatment prevented LPS-induced renal pathogenic changes in the BDL-Pio+LPS group. Activation of systemic, renal vessel and renal tissue levels of PPARγ by chronic pioglitazone treatment has beneficial effects on the endotoxemia-related TNFα/NFκB-mediated acute and chronic renal inflammation in cirrhosis. This study revealed that normalization of renal and renal arterial levels of PPARγ effectively prevented LPS-induced acute and chronic renal dysfunction in cirrhotic ascitic rats.
format	article
author	Szu-Yu Liu Chia-Chang Huang Shiang-Fen Huang Tsai-Ling Liao Nai-Rong Kuo Ying-Ying Yang Tzu-Hao Li Chih-Wei Liu Ming-Chih Hou Han-Chieh Lin
author_facet	Szu-Yu Liu Chia-Chang Huang Shiang-Fen Huang Tsai-Ling Liao Nai-Rong Kuo Ying-Ying Yang Tzu-Hao Li Chih-Wei Liu Ming-Chih Hou Han-Chieh Lin
author_sort	Szu-Yu Liu
title	Pioglitazone Ameliorates Acute Endotoxemia-Induced Acute on Chronic Renal Dysfunction in Cirrhotic Ascitic Rats
title_short	Pioglitazone Ameliorates Acute Endotoxemia-Induced Acute on Chronic Renal Dysfunction in Cirrhotic Ascitic Rats
title_full	Pioglitazone Ameliorates Acute Endotoxemia-Induced Acute on Chronic Renal Dysfunction in Cirrhotic Ascitic Rats
title_fullStr	Pioglitazone Ameliorates Acute Endotoxemia-Induced Acute on Chronic Renal Dysfunction in Cirrhotic Ascitic Rats
title_full_unstemmed	Pioglitazone Ameliorates Acute Endotoxemia-Induced Acute on Chronic Renal Dysfunction in Cirrhotic Ascitic Rats
title_sort	pioglitazone ameliorates acute endotoxemia-induced acute on chronic renal dysfunction in cirrhotic ascitic rats
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/103438a3d81240c499a61e067294950a
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Pioglitazone Ameliorates Acute Endotoxemia-Induced Acute on Chronic Renal Dysfunction in Cirrhotic Ascitic Rats

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