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and quinones and semiquinones, which are intermediates of melanin biosynthesis, are mutagenic with the capacity to cause cytogenetic instability

Abbreviations MDA: Malondialdehyde ROS: Reactive oxygen species OS: Oxidative stress GSH: Glutathione CKD: Chronic kidney disease CRF: Chronic renal failure ECM: Extracellular matrix STING: Stimulator of interferon genes mtDNA: Mitochondrial DNA ATP: Adenosine triphosphate HE: Hematoxylin and eosin PAS: Periodic acidSchiff cGAS: Cyclic GMPAMP synthase MTT: Methylthiazolyltetrazolium TUNEL: Terminal deoxynucleotidyl transferase dUTP nick-end labeling SOD: Superoxide dismutase SCR: Serum creatinine UPR: Urinary protein IL: Interleukin TNF-: Tumor necrosis factor- Hyp: Hydroxyproline MMP: Matrix metalloproteinase LC3B: Microtubule-associated proteins 1A/1B light chain 3B Col-1: Collagen I -SMA: -Smooth muscle actin FN: Fibronectin ATG5: Autophagy-related 5 p62: Sequestosome 1 TBK1: TANK-binding kinase 1 IRF3: Interferon regulatory factor 3 BCL-2: B cell lymphoma-2 BAX: BCL-2-associated X protein GFR: Glomerular filtration rate dsDNA: Double-stranded DNA cGAMP: Cyclic GMPAMP DAMPs: Damage-associated molecular patterns References Ahmed A, Trezza A, Gentile M, Paccagnini E, Lupetti P, Spiga O et al (2022) The drp-1-mediated mitochondrial fission inhibitor mdivi-1 impacts the function of ion channels and pathways underpinning vascular smooth muscle tone

Considerations: Topical treatments are ideal for mild to moderate pigmentation and can be used alongside other treatments for enhanced effects

Gastrointestinal effects Nausea is the most common side effect, affecting roughly 41% of participants in the REDEFINE 1 trial

n = 5, analyzed by one-way ANOVA with post-hoc Tukeys t-tests