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

TL;DR

Pentoxifylline protects against kidney and liver damage caused by amikacin in mice, offering a safer treatment option.

Contribution

Pentoxifylline at 100 mg/kg completely prevents amikacin-induced nephrotoxicity and hepatotoxicity in mice.

Findings

Co-treatment with pentoxifylline normalized biochemical markers and reduced oxidative stress caused by amikacin.

Pentoxifylline at 100 mg/kg fully restored kidney and liver tissue architecture damaged by amikacin.

Pentoxifylline showed dose-dependent efficacy in mitigating amikacin toxicity without affecting its antimicrobial action.

Abstract

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.

PTX effectively prevents both nephrotoxicity and hepatotoxicity induced by AMK. Complete organ protection at 100 mg/kg PTX, with normalization of biochemical markers, oxidative stress, and histopathology.PTX is proposed as a safe, adjunctive therapy to enhance AMK safety without compromising its antimicrobial efficacy, addressing a critical need in antibiotic stewardship.

PTX effectively prevents both nephrotoxicity and hepatotoxicity induced by AMK.

Complete organ protection at 100 mg/kg PTX, with normalization of biochemical markers, oxidative stress, and histopathology.

PTX is proposed as a safe, adjunctive therapy to enhance AMK safety without compromising its antimicrobial efficacy, addressing a critical need in antibiotic stewardship.

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