Key role of organic cation transporter 2 for the nephrotoxicity effect of triptolide in rheumatoid arthritis

Shen, Qingqing; Wang, Jingjing; Yuan, Ziqiao; Jiang, Zhijun; Shu, Ting; Xu, Dengqiu; He, Junqi; Zhang, Luyong; Huang, Xin

doi:10.1016/j.intimp.2019.105959

Cited by 15 publications

(6 citation statements)

References 53 publications

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“…Another very small human study using the OCT2 inhibitor pantoprazole (proton-pump inhibitor) could not ameliorate cisplatin-caused nephrotoxicity in pediatric and adolescent cancer patients [ 123 ]. In rodents, it has been indicated that the drug-induced kidney injury incurred by the aminoglycoside gentamicin [ 18 ], triptolide [ 124 ], and the plant toxin ochratoxin A [ 125 ] was dependent on Oct2 expression and function. In vitro data also suggest that the nephrotoxic effects of the antiviral agents defovir, cidofovir, and tenofovir [ 126 ], and the anticancer agent ifosfamide also underlie OCT2 uptake [ 127 ].…”

Section: Octs In the Kidneymentioning

confidence: 99%

Organic Cation Transporters in Human Physiology, Pharmacology, and Toxicology

Samodelov

Kullak‐Ublick

Gai

et al. 2020

IJMS

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Individual cells and epithelia control the chemical exchange with the surrounding environment by the fine-tuned expression, localization, and function of an array of transmembrane proteins that dictate the selective permeability of the lipid bilayer to small molecules, as actual gatekeepers to the interface with the extracellular space. Among the variety of channels, transporters, and pumps that localize to cell membrane, organic cation transporters (OCTs) are considered to be extremely relevant in the transport across the plasma membrane of the majority of the endogenous substances and drugs that are positively charged near or at physiological pH. In humans, the following six organic cation transporters have been characterized in regards to their respective substrates, all belonging to the solute carrier 22 (SLC22) family: the organic cation transporters 1, 2, and 3 (OCT1–3); the organic cation/carnitine transporter novel 1 and 2 (OCTN1 and N2); and the organic cation transporter 6 (OCT6). OCTs are highly expressed on the plasma membrane of polarized epithelia, thus, playing a key role in intestinal absorption and renal reabsorption of nutrients (e.g., choline and carnitine), in the elimination of waste products (e.g., trimethylamine and trimethylamine N-oxide), and in the kinetic profile and therapeutic index of several drugs (e.g., metformin and platinum derivatives). As part of the Special Issue Physiology, Biochemistry, and Pharmacology of Transporters for Organic Cations, this article critically presents the physio-pathological, pharmacological, and toxicological roles of OCTs in the tissues in which they are primarily expressed.

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Section: Octs In the Kidneymentioning

confidence: 99%

Organic Cation Transporters in Human Physiology, Pharmacology, and Toxicology

Samodelov

Kullak‐Ublick

Gai

et al. 2020

IJMS

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“…Ideally, toxicity data should be the result of the clinical performance of the drug, but this is a costly way to collect data and the amount of data is small. In vivo animal-based toxicity studies and in vitro cell and tissue-based toxicity studies can also provide more reliable toxicity data [ 15 ]. At present, some government and research institutions in the United States have joined forces to build a more authoritative database on the toxicity of TW, while countries and regions such as Europe and Japan have also established databases related to the safety of TW.…”

Section: Introductionmentioning

confidence: 99%

Evaluation Analysis of the Nephrotoxicity of Tripterygium wilfordii Preparations with CONSORT Harms Statement Based on Deep Learning

Qi¹,

Chen²,

Chen

et al. 2022

Journal of Healthcare Engineering

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In this paper, the safety of Tripterygium wilfordii polyglycoside (TW) preparation was evaluated by combining literature research and evidence-based evaluation research, so as to provide evidence-based safety information of Tripterygium wilfordii polyglycoside preparation (nephroptosis) for government decision making and clinical application. In this paper, we propose a network structure inspired by the LSTM gate mechanism. All the research methods of the included references are evaluated by internationally recognized evaluation tools or standards. Prevalence was analyzed according to the type of intervention (e.g., time of administration) and route of administration. The results of this experiment provide methods and suggestions for the evaluation of traditional Chinese medicine nephroptosis in the future.

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“…Triptolide (TP), a diterpene triepoxide isolated from Tripterygium wilfordii Hook F, has been widely used to treat inflammatory and autoimmune diseases, such as systemic lupus erythematosus and RA, but its severe systemic toxicity, especially hepatotoxicity, nephrotoxicity, and cardiotoxicity, along with poor solubility, results in a narrow therapeutic window and poor bioavailability that limit its clinical application (Shen et al., 2019 ; Song et al., 2020 ; Liaw et al., 2021 ; Liu et al., 2021 ). TP has been demonstrated to exhibit anti-inflammatory and immunosuppressive activities, and TP derivatives have been demonstrated to inhibit the polarization of macrophages into the proinflammatory M1 phenotype (Shen et al., 2019 ; Fu et al., 2020 ; Liaw et al., 2021 ; Liu et al., 2021 ). Folic acid (FA)-modified liposomes (FA-Lips) have been demonstrated to have enhanced targeting efficiency by binding to FR with high affinity (Nogueira et al., 2015 ; Xue et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%