Thioxanthone-Mediated Cytoprotection Against Cisplatin Toxicity: Exploring the Potential Involvement of P-Glycoprotein Through Computational and Experimental Approaches
Jéssica Veiga-Matos, Daniel J. V. A. dos Santos, Andreia Palmeira, Emília Sousa, Ana I. Morales, Marta Prieto, Fernando Remião, Renata Silva
TL;DR
This study explores how thioxanthones may protect kidney cells from cisplatin toxicity by enhancing P-glycoprotein activity.
Contribution
The study combines computational and experimental methods to investigate thioxanthone effects on P-gp in renal cells.
Findings
TX2 significantly increased P-gp transport activity and expression in HK-2 cells.
TX2 provided strong protection against cisplatin-induced cytotoxicity in kidney cells.
Computational models identified specific binding sites for thioxanthones within P-gp.
Abstract
P-glycoprotein (P-gp), an efflux transporter highly expressed in renal tubules, plays a crucial role in the detoxification and protection of barrier/excretory tissues from harmful xenobiotics. Xanthones and thioxanthones (TXs) are known for their antimicrobial and antitumor activities and for their ability to modulate membrane transporters such as P-gp. Previous studies have reported that (thio)xanthonic derivatives enhance P-gp expression and/or activity in intestinal cells, reducing the intracellular accumulation of toxic substrates; however, their capacity to modulate P-gp in renal cells remains poorly explored. This study aimed to predict, in silico, TXs’ binding sites within P-gp and to evaluate, in vitro, in human kidney (HK)-2 cells, the effects of selected TXs (TX1–5) on P-gp activity and expression, and protection against cisplatin-induced cytotoxicity. Computational studies…
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
Click any figure to enlarge with its caption.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12
Figure 13
Figure 14
Figure 15
Figure 16
Figure 17
Figure 18
Figure 19
Figure 20
Figure 21
Figure 22
Figure 23
Figure 24
Figure 25
Figure 26
Figure 27
Figure 28
Figure 29
Figure 30
Figure 31
Figure 32Peer Reviews
No public reviews on file for this paper yet. If you reviewed it on a platform where reviews are public (OpenReview, ICLR, NeurIPS, ICML), you can paste yours below so the community can read it here.
Videos
No videos yet. Explain this paper in a talk, walkthrough, or lecture? Add one.
Taxonomy
TopicsDrug Transport and Resistance Mechanisms · Natural Compound Pharmacology Studies · Chemotherapy-induced organ toxicity mitigation