Alterations in Adenylate Nucleotide Metabolism and Associated Lipid Peroxidation and Protein Oxidative Damage in Rat Kidneys Under Combined Acetaminophen Toxicity and Protein Deficiency

Acetaminophen (APAP) overdose is a major cause of acute liver failure and can be fatal, often without early symptoms. Protein deficiency, arising from illness or inadequate diet, impairs growth, immunity, and tissue repair. Both conditions can harm the kidneys, yet the impact of energy imbalance on renal physiology remains unclear. In this study, APAP toxicity and a low-protein diet induced behavioral suppression and tissue damage, as evidenced by reduced whole-body, liver, and kidney weights in rats. In kidney mitochondria of rats exposed to only toxic APAP doses, ATP levels declined sharply while ADP and AMP increased. AMP deaminase and ATPases' activities rose about twofold and 1.5-fold, respectively, whereas cytosolic 5 '-nucleotidase activity fell nearly threefold, suggesting compensatory responses to disrupted energy balance. The strongest reductions in ATP and the greatest increases in AMP and ATPase activity occurred in APAP-intoxicated rats fed a low-protein diet. This combination also intensified lipid peroxidation and oxidative protein damage, evidenced by elevated TBARS, reduced protein SH-groups, and increased protein carbonyls. Overall, APAP intoxication with protein deficiency disrupts renal energy metabolism, leading to mitochondrial dysfunction and structural kidney injury. Nutritional status therefore critically influences drug-induced nephrotoxicity, and antioxidant strategies may help prevent damage under metabolic stress.