{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:43:26Z","timestamp":1788587006663,"version":"build-2803163510"},"reference-count":61,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T00:00:00Z","timestamp":1636070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["MOST 109-2314-B-010-032-MY3&MOST-110-2511-H-A491-504-MY3"],"award-info":[{"award-number":["MOST 109-2314-B-010-032-MY3&MOST-110-2511-H-A491-504-MY3"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011912","name":"Taipei Veterans General Hospital","doi-asserted-by":"publisher","award":["V110C-033"],"award-info":[{"award-number":["V110C-033"]}],"id":[{"id":"10.13039\/501100011912","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Endotoxemia-activated tumor necrosis factor (TNF\u03b1)\/nuclear factor kappa B (NF\u03baB) signals result in acute on chronic inflammation-driven renal dysfunction in advanced cirrhosis. Systemic activation of peroxisome proliferator-activated receptor gamma (PPAR\u03b3) 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 PPAR\u03b3 expression, upregulated renal inflammatory markers (TNF\u03b1, NF\u03baB, 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 TNF\u03b1-NF\u03baB-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 PPAR\u03b3 by chronic pioglitazone treatment has beneficial effects on the endotoxemia-related TNF\u03b1\/NF\u03baB-mediated acute and chronic renal inflammation in cirrhosis. This study revealed that normalization of renal and renal arterial levels of PPAR\u03b3 effectively prevented LPS-induced acute and chronic renal dysfunction in cirrhotic ascitic rats.<\/jats:p>","DOI":"10.3390\/cells10113044","type":"journal-article","created":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T20:41:14Z","timestamp":1636317674000},"page":"3044","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Pioglitazone Ameliorates Acute Endotoxemia-Induced Acute on Chronic Renal Dysfunction in Cirrhotic Ascitic Rats"],"prefix":"10.3390","volume":"10","author":[{"given":"Szu-Yu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Medical Education, Medical Innovation and Research Office (MIRO), Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1313-4628","authenticated-orcid":false,"given":"Chia-Chang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Education, Medical Innovation and Research Office (MIRO), Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0390-9108","authenticated-orcid":false,"given":"Shiang-Fen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsai-Ling","family":"Liao","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei 11217, Taiwan"},{"name":"Department of Medical Research, Taichung Veterans General Hospital, Taichung 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nai-Rong","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Medical Education, Medical Innovation and Research Office (MIRO), Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7719-0397","authenticated-orcid":false,"given":"Ying-Ying","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Education, Medical Innovation and Research Office (MIRO), Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Hao","family":"Li","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei 11217, Taiwan"},{"name":"Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Foundation, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Chih","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Chieh","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1111\/apt.13571","article-title":"Differential visceral blood flow in the hyperdynamic circulation of patients with liver cirrhosis","volume":"43","author":"McAvoy","year":"2016","journal-title":"Aliment. 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