| アブストラクト | AIMS: Peroxisome proliferator-activated receptor-alpha (PPARalpha) levels are markedly lower in the kidneys of chronic kidney disease (CKD) patients. Fibrates (PPARalpha agonists) are therapeutic agents against hypertriglyceridemia and potentially against CKD. However, conventional fibrates are eliminated by renal excretion, limiting their use in patients with impaired renal function. Here, we aimed to evaluate the renal risks associated with conventional fibrates via clinical database analysis and investigate the renoprotective effects of pemafibrate, a novel selective PPARalpha modulator mainly excreted into the bile. MAIN METHODS: The risks associated with conventional fibrates (fenofibrate, bezafibrate) to the kidneys were evaluated using the Food and Drug Administration Adverse Event Reporting System. Pemafibrate (1 or 0.3 mg/kg/day) was administered daily using an oral sonde. Its renoprotective effects were examined in unilateral ureteral obstruction (UUO)-induced renal fibrosis model mice (UUO mice) and adenine-induced CKD model mice (CKD mice). KEY FINDINGS: The ratios of glomerular filtration rate decreased and blood creatinine increased were markedly higher after conventional fibrate use. Pemafibrate administration suppressed increased gene expressions of collagen-I, fibronectin, and interleukin 1 beta (IL-1beta) in the kidneys of UUO mice. In CKD mice, it suppressed increased plasma creatinine and blood urea nitrogen levels and decreased red blood cell count, hemoglobin, and hematocrit levels, along with renal fibrosis. Moreover, it inhibited the upregulation of monocyte chemoattractant protein-1, IL-1beta, tumor necrosis factor-alpha, and IL-6 in the kidneys of CKD mice. SIGNIFICANCE: These results demonstrated the renoprotective effects of pemafibrate in CKD mice, confirming its potential as a therapeutic agent for renal disorders. |
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| ジャーナル名 | Life sciences |
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| 投稿日 | 2023/3/21 |
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| 投稿者 | Horinouchi, Yuya; Murashima, Yuka; Yamada, Yuto; Yoshioka, Shun; Fukushima, Keijo; Kure, Takumi; Sasaki, Naofumi; Imanishi, Masaki; Fujino, Hiromichi; Tsuchiya, Koichiro; Shinomiya, Kazuaki; Ikeda, Yasumasa |
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| 組織名 | Department of Pharmaceutical Care and Clinical Pharmacy, Faculty of;Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan. Electronic;address: horinouchi@ph.bunri-u.ac.jp.;Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.;Department of Pharmacology for Life Sciences, Graduate School of Pharmaceutical;Sciences & Graduate School of Biomedical Sciences, Tokushima University,;Tokushima, Japan.;Department of Medical Pharmacology, Graduate School of Pharmaceutical Sciences &;Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.;Department of Pharmacology, Institute of Biomedical Sciences, Tokushima;University Graduate School, Tokushima, Japan. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/36940907/ |
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