Amikacin toxicity revisited: pentoxifylline offers protection in high-risk treatment scenarios

Amikacin (AMK), a potent aminoglycoside antibiotic, is clinically valuable for severe Gram-negative infections but is limited by its nephrotoxic and hepatotoxic effects, primarily mediated through oxidative stress and inflammation. This study investigated the protective role of pentoxifylline (PTX), a methylxanthine derivative with antioxidant and anti-inflammatory properties, against AMK-induced organ damage in male BALB/c mice. Thirty mice were divided into six groups: control, AMK (100 mg/kg/day), PTX monotherapy (50 or 100 mg/kg/day), and AMK combined with PTX (50 or 100 mg/kg/day). After 28 days, biochemical, oxidative stress, inflammatory, and histopathological analyses were conducted. AMK administration significantly elevated renal (BUN and creatinine) and hepatic (ALT, AST and ALP) markers, increased oxidative stress (MDA), and upregulated inflammatory cytokines (IL-17), alongside histopathological damage in kidney and liver tissues. Co-treatment with PTX, particularly at 100 mg/kg, normalized these parameters, restored antioxidant defenses, reduced inflammation, and preserved tissue architecture. PTX demonstrated dose-dependent efficacy, with the higher dose offering complete protection against AMK-induced toxicity. These findings highlighted PTX's potential as an adjunctive therapy to mitigate AMK-associated nephrotoxicity and hepatotoxicity, suggesting its clinical utility in optimizing aminoglycoside safety without compromising efficacy.