Article
Food Science & Technology
Cindy Nguyen, Amanda J. Edgley, Darren J. Kelly, Andrew R. Kompa
Summary: This study investigates the effects of the uremic toxin indoxyl sulfate (IS) on vascular endothelial function and redox balance. The results indicate that IS impairs endothelium-dependent relaxation and increases the expression of oxidative stress markers. Inhibition of the aryl hydrocarbon receptor (AhR) could be a potential therapy for cardiovascular disease in the context of chronic kidney disease (CKD).
Article
Plant Sciences
Yenan Mo, Dongmei Hu, Wanlin Yu, Chunlan Ji, Yin Li, Xusheng Liu, Zhaoyu Lu
Summary: This study found that Astragaloside IV (AS-IV), a component of Astragalus membranaceus, can reduce indoxyl sulfate (IS)-induced renal tubular injury by inhibiting the expression of aryl hydrocarbon receptor (AhR). This offers a new therapeutic approach to the treatment of chronic renal failure.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Shinichi Saito, Yoshihiro Koya, Hiroaki Kajiyama, Mamoru Yamashita, Akihiro Nawa
Summary: Although platinum-combination chemotherapy shows a high response rate at the primary site, the treatment of epithelial ovarian cancer (EOC) remains challenging due to tumor recurrence and metastasis. Recent studies have revealed that chemotherapy paradoxically promotes cancer cell survival, proliferation, and metastasis, and the underlying molecular mechanisms need to be elucidated for effective therapeutic strategies.
LABORATORY INVESTIGATION
(2023)
Article
Medicine, Research & Experimental
Keisuke Nakagawa, Mayuko Itoya, Nao Takemoto, Yuika Matsuura, Masashi Tawa, Yasuo Matsumura, Mamoru Ohkita
Summary: This study showed that IS increases O-2(-) production in vascular tissues, attenuating ACh- and SNP-induced vasorelaxation via potential NO inactivation. Additionally, IS-promoted O-2(-) production in the presence of vascular endothelium is likely through binding to AhR and activation of NADPH oxidase.
Article
Multidisciplinary Sciences
Jessica Felicio Andrade, Maria Dalboni, Otavio Candido Clemente, Beatriz Moreira Silva, Barbara Formaggio Domingues, Adelson Marcal Rodrigues, Maria Eugenia Canziani, Abolfazl Zarjou, Miguel Cendoroglo, Miguel Angelo Goes
Summary: This study compares the clinical data and serum levels of sFas, EPO, and pro-inflammatory markers between patients with non-dialytic CKD (NDD-CKD) and healthy subjects. It also evaluates the relationship between serum EPO, sFas levels, anemia, and outcomes in NDD-CKD patients over a long follow-up period. The findings suggest that serum sFas levels, along with age and diabetes, are independently associated with kidney anemia for an extended period.
Article
Multidisciplinary Sciences
Takeshi Masaki, Makoto Okazawa, Ryotaro Asano, Tadakatsu Inagaki, Tomohiko Ishibashi, Akiko Yamagishi, Saori Umeki-Mizushima, Manami Nishimura, Yusuke Manabe, Hatsue Ishibashi-Ueda, Manabu Shirai, Hirotsugu Tsuchimochi, James T. Pearson, Atsushi Kumanogoh, Yasushi Sakata, Takeshi Ogo, Tadamitsu Kishimoto, Yoshikazu Nakaoka
Summary: This study investigates the role of the aryl hydrocarbon receptor (AHR) in the pathogenesis of pulmonary arterial hypertension (PAH), revealing that AHR agonistic activity is associated with poor prognosis in PAH patients. The findings suggest that AHR plays crucial roles in the development and progression of PAH, highlighting the AHR-signaling pathway as a potential therapeutic target for PAH.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Geriatrics & Gerontology
Lara Caldiroli, Silvia Armelloni, Alessandra Eskander, Piergiorgio Messa, Vittoria Rizzo, Elisabetta Margiotta, Matteo Cesari, Simone Vettoretti
Summary: In a cross-sectional study of 93 patients with chronic kidney disease, it was found that indoxyl sulfate (IS) and p-cresyl sulfate (PCs) were not associated with sarcopenia, although they were linked to certain inflammatory pathways. Particularly, p-cresyl sulfate was positively associated with the Protein Energy Wasting syndrome (PEW).
EXPERIMENTAL GERONTOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Chien-Lin Lu, Cai-Mei Zheng, Kuo-Cheng Lu, Min-Tser Liao, Kun-Lin Wu, Ming-Chieh Ma
Summary: The uremic toxin IS leads to oxidative stress in CKD patients, causing organ damage and complications such as cardiovascular diseases, renal osteodystrophy, muscle wasting, and anemia. IS-induced ROS production impairs glomerular filtration and triggers vascular smooth muscle cells transformation, contributing to muscle atrophy and bone abnormalities.
Article
Biochemistry & Molecular Biology
Li-Ting Tsai, Te- Weng, Ting-Yu Chang, Kuo-Cheng Lan, Chih-Kang Chiang, Shing-Hwa Liu
Summary: The accumulation of the uremic toxin indoxyl sulfate (IS) is a key pathological feature of chronic kidney disease (CKD). Exposure to IS can induce ferroptosis, characterized by iron accumulation, impaired antioxidant system, elevated reactive oxygen species (ROS) levels, and lipid peroxidation. IS triggers intracellular iron accumulation and ROS generation, leading to the induction of ferroptosis, senescence, ER stress, and injury/fibrosis in CKD kidneys.
Review
Pharmacology & Pharmacy
Colleen S. Curran, Jeffrey B. Kopp
Summary: The aryl hydrocarbon receptor (AHR) plays an important role in the development of chronic kidney disease (CKD) by binding various endogenous and xenobiotic ligands and regulating kidney stability, transcriptional activity, and cell signaling. AHR activity is closely associated with kidney damage and protection, with its cross-talk with estrogen, peroxisome proliferator-activated receptor-gamma, and NF-kappa B pathways contributing to the diversity of AHR responses in different forms and stages of CKD. Understanding the roles of AHR in kidney fibrosis, metabolism, and the renin-angiotensin system can provide insights into the pathogenesis and therapies of CKD.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lung-Chih Li, Wei-Yu Chen, Jin-Bor Chen, Wen-Chin Lee, Chiung-Chih Chang, Hong-Tai Tzeng, Chiang-Chi Huang, Ya-Jen Chang, Jenq-Lin Yang
Summary: Research revealed that the uremic toxin IS plays a crucial role in chronic kidney disease, triggering neuroinflammation and leading to cognitive impairment. Experimental results showed that AST-120 effectively reduced IS levels and reversed cognitive impairment. NLRP3 gene knockout mice did not show changes in cognitive function, further confirming the impact of IS on cognition through NLRP3 mediation.
Article
Biochemistry & Molecular Biology
Meei-Ling Sheu, Liang-Yi Pan, Cheng-Ning Yang, Jason Sheehan, Liang-Yu Pan, Weir-Chiang You, Chien-Chia Wang, Hung-Chuan Pan
Summary: Thrombin is closely related to neurodegenerative disorders, and AhR is well expressed in microglia cells involved in inflammatory disorders of the brain. This study found that deleting AhR aggravated the inflammatory response and neurodegenerative processes induced by thrombin in microglia cells, while an AhR agonist could inhibit these responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Food Science & Technology
Ebru Melekoglu, F. Gulhan Samur
Summary: Chronic kidney disease is linked to changes in composition and function of gut microbiota. Dietary fiber restriction contributes to gut dysbiosis and formation of gut-derived uremic toxins.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
(2023)
Article
Biochemistry & Molecular Biology
George Chang, Hong-Mou Shih, Chi-Feng Pan, Chih-Jen Wu, Cheng-Jui Lin
Summary: Studies have shown that a low-protein diet supplemented with ketoanalogs (KAs) can significantly slow down the progression of renal function in patients with stages 3-5 chronic kidney disease (CKD). However, it is unclear how it affects endothelial function and serum levels of protein-bound uremic toxins. This study aimed to investigate the effects of a low-protein diet supplemented with KAs on kidney function, endothelial function, and serum uremic toxin levels in a cohort of CKD patients. The results demonstrated that LPD supplemented with KAs significantly preserved kidney function and improved endothelial function and protein-bound uremic toxins in patients with CKD.
Review
Biochemistry & Molecular Biology
Kuo-Chin Hung, Wei-Cheng Yao, Yi-Lien Liu, Hung-Jen Yang, Min-Tser Liao, Keong Chong, Ching-Hsiu Peng, Kuo-Cheng Lu
Summary: Patients with chronic kidney disease (CKD) often have a high accumulation of protein-bound uremic toxins (PBUTs), such as indoxyl sulfate (IS) and p-cresyl sulfate (pCS). The buildup of PBUTs inhibits bone and muscle function, worsens muscle wasting, and contributes to low bone turnover disorders. Understanding the underlying mechanisms of bone and muscle loss in CKD can aid in developing new therapies for musculoskeletal diseases.