Cui, Sheng Luo, Kang Quan, Yi Lim, Sun Woo Shin, Yoo Jin Lee, Kyung Eun Kim, Hong Lim Ko, Eun Jeong Kim, Ju Hwan Chung, Sang J. Bae, Soo Kyung Ha Chung, Byung Yang, Chul Woo 2024-01-19T14:04:18Z 2024-01-19T14:04:18Z 2022-01-10 2021-07 1226-3303 https://pubs.kist.re.kr/handle/201004/116714 Background/Aims: Coenzyme Q(10 )(CoQ(10)), is a promising antioxidant; however, low bioavailability owing to lipid-solubility is a limiting factor. We developed water-soluble COQ(10) (CoQ(10)-W) and compared its effects with conventional lipid-soluble CoQ(10) (CoQ(10) -L) in an experimental model of chronic tacrolimus (Tac) nephropathy. Methods: CoQ(10) -W was developed from a glycyrrhizic-carnitine mixed layer CoQ(10) micelle based on acyltransferases. Chronic nephropathy was induced in rats with 28-day Tac treatment; they were concomitantly treated with CoQ(10) -L or CoQ(10) -W. CoQ(10) level in plasma and kidney were measured using liquid chromatography-mass spectrometry. CoQ(10) -W and CoQ(10) -L effects on Tac-induced nephropathy were assessed in terms of renal function, histopathology, oxidative stress, and apoptotic cell death. Their effects on cell viability and reactive oxygen species (ROS) production were assessed in cultured proximal tubular cells, human kidney 2 (HK-2) cells. Results: The plasma CoQ(10) level was significantly higher in the CoQ(10) -W group than in the CoQ(10)-L group. Tac treatment caused renal dysfunction, typical pathologic lesions, and oxidative stress markers. Serum creatinine was restored in the Tac + CoQ(10) -L or CoQ(10) -W groups compared with that in the Tac group. CoQ(10) -W administration reduced oxidative stress and apoptosis markers. Mitochondrial ultrastructure assessment revealed that the addition of CoQ(10) -L or CoQ(10)-W with Tac increased mitochondrial size and number than Tac treatment alone. In vitro investigations revealed that both CoQ(10) -L and CoQ(10)-W improved cell viability and reduced ROS production in the Tac-induced HK-2 cell injury. Conclusions: CoQ(10) -W has a better therapeutic effect in Tac-induced renal injury than conventional CoQ(10) -L, possibly associated with improved CoQ(10) bioavailability. English KOREAN ASSOC INTERNAL MEDICINE CHRONIC CYCLOSPORINE NEPHROPATHY EXPRESSION KLOTHO Water-soluble coenzyme Q(10) provides better protection than lipid-soluble coenzyme Q(10) in a rat model of chronic tacrolimus nephropathy Article 10.3904/kjim.2020.211 1 KOREAN JOURNAL OF INTERNAL MEDICINE, v.36, no.4, pp.949 - 961 KOREAN JOURNAL OF INTERNAL MEDICINE 36 4 949 961 scie scopus kci ART002728523 000669004600025 2-s2.0-85105496985 Medicine, General & Internal General & Internal Medicine Article CHRONIC CYCLOSPORINE NEPHROPATHY EXPRESSION KLOTHO Tacrolimus Coenzyme Q(10) Water-soluble coenzyme Q(10) Kidney Oxidative stress