N-Acetylcysteine Attenuates Amikacin-Induced Biochemical, Inflammatory, and Histopathological Alterations in Mice

Background: Amikacin is an effective aminoglycoside antibiotic, but its clinical use is limited by nephrotoxicity, hepatotoxicity, and neurotoxicity. N-acetylcysteine (NAC), a glutathione precursor and antioxidant, may help reduce these side effects. This study evaluated whether NAC attenuated selected amikacin-induced biochemical, inflammatory, and histopathological alterations in mice. Methods: Male Swiss albino mice were divided into four groups: control, amikacin, NAC, and amikacin-NAC, and the behavioral performance was assessed using the light-dark box test. Serum samples were collected for measurements of kidney and liver biomarkers, metabolic markers, and electrolytes (calcium, inorganic phosphate, and uric acid). A multiplex cytokine/chemokine panel was used to assess the effects of amikacin with/without NAC on systemic inflammation. Results: Amikacin-treated mice showed a reduction in the time spent in the light area, and this effect was improved by NAC. Amikacin also altered certain biochemistry parameters, increasing levels of aspartate transferase and albumin; these changes were attenuated by NAC. Amikacin caused marked increases in certain inflammatory cytokines and chemokines, including IL-6, IL-12p70, IL-22, IL-18, CXCL10, and CCL11. Treatment with NAC lowered IL-6, IL-12p70, IL-22, IL-18, CXCL10, and CCL11. The sparse partial least squares discriminant and heatmap analysis of the serum inflammatory profile revealed segregation of the amikacin group from the other three groups. Importantly, the histopathological assays on renal and cerebral cortex showed NAC caused improvements, with well-shaped tissues, attenuating the cortical histopathological alterations observed in animals treated with amikacin. Conclusions: These findings suggest that NAC may have the potential to attenuate certain biochemical, inflammatory, and histopathological alterations associated with high-dose amikacin exposure.