Supplementary material The Supplementary Material for this article can be found online at: Abbreviations AQ amodiaquine AQ-SG 5-glutathion- S -yl-amodiaquine AQ-QI amodiaquine-quinoneimine BSO L -buthionine-sulfoximine CDNB 1-chloro-2, 4-dinitrobenzene CYP cytochromes P450 DEAQ N -desethylamodiaquine DEAQ-SG 5-glutathion- S -yl- N -desethylamodiaquine DEAQ-QI N -desethylamodiaquine-quinoneimine DMEM Dulbeccos modified Eagle medium DMF N,N -dimethylformamide ER endoplasmic reticulum FBS fetal bovine serum GSH glutathione GSSG glutathione disulfide GST glutathione S -transferase H 2 O 2 hydrogen peroxide HClO 4 perchloric acid HRP horseradish peroxidase NQO1 NAD(P)H:quinone oxidoreductase 1 NAPQI N -acetyl- p -benzoquinonimine PBS phosphate-buffered saline QI quinoneimine

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Increased fluid intake can dilute serum electrolytes, particularly sodium, leading to conditions such as hyponatremia if not balanced by appropriate sodium excretion
Unlike earlier GLP-1 receptor agonists like semaglutide (Ozempic/Wegovy) that target a single hormone pathway, or tirzepatide (Mounjaro/Zepbound) that targets two, retatrutide activates three distinct metabolic receptors : GIP, GLP-1, and glucagon
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