Association Between the Dietary Inflammatory Index (DII) and Head and Neck Cancer Incidence-A Narrative Review.

Rhabdomyolysis-associated acute kidney injury is a severe clinical complication resulting from extensive skeletal muscle breakdown and the subsequent release of intracellular constituents, particularly myoglobin, creatine kinase, and lactate dehydrogenase, into the circulation [,]. In experimental settings, intramuscular glycerol administration is widely used to reproduce this condition because it induces myofiber damage followed by myoglobin-mediated renal injury []. Filtered myoglobin accumulates within the renal tubules, where its heme component promotes vasoconstriction, tubular obstruction, iron-dependent reactive oxygen species generation, lipid peroxidation, mitochondrial injury, and direct tubular epithelial toxicity [,]. These events impair renal filtration and are accompanied by elevations in creatinine, urea, cystatin C, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin, together with tubular degeneration, cast formation, inflammatory infiltration, and acute tubular necrosis [,]. At the molecular level, rhabdomyolysis-associated renal injury is sustained by interconnected redox, inflammatory, mitochondrial, and regulated cell death pathways. Excessive reactive oxygen species overwhelm endogenous antioxidant defenses and disturb the Keap1/Nrf2 signaling axis, thereby reducing the activity of protective enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and reduced glutathione [,]. Oxidative injury also activates NF-κB-dependent inflammatory signaling and increases pro-inflammatory cytokine production. In parallel, mitochondrial stress and damage-associated signals can activate the NLRP3 inflammasome and gasdermin D-mediated pyroptosis, while disruption of SIRT1/AMPK/PGC-1α-dependent mitochondrial regulation promotes energetic failure and structural instability. Persistent mitochondrial dysfunction further shifts the Bax/Bcl-2 balance toward caspase-dependent apoptosis, thereby amplifying tubular epithelial loss []. Because these pathogenic processes are highly interconnected, interventions directed at only one pathway may provide incomplete protection. A therapeutic strategy capable of simultaneously restoring antioxidant defenses, suppressing inflammatory and pyroptotic signaling, preserving mitochondrial homeostasis, and limiting apoptosis may therefore be more effective in attenuating rhabdomyolysis-associated renal injury. This has encouraged growing interest in plant-derived bioactive compounds and redox-active trace elements with complementary cytoprotective properties [].