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

Area of Science:

• Pharmacology and Toxicology
• Nephrology and Hepatology
• Inflammation and Oxidative Stress Research

Background:

• Amikacin (AMK), a critical antibiotic for Gram-negative infections, causes significant nephrotoxicity and hepatotoxicity.
• This organ damage is primarily driven by oxidative stress and inflammatory pathways.
• Pentoxifylline (PTX), known for its antioxidant and anti-inflammatory effects, is a potential therapeutic agent.

Purpose of the Study:

• To evaluate the protective effects of pentoxifylline (PTX) against amikacin (AMK)-induced nephrotoxicity and hepatotoxicity.
• To investigate the underlying mechanisms involving oxidative stress and inflammation.
• To determine the dose-dependent efficacy of PTX as an adjunctive therapy.

Main Methods:

• Male BALB/c mice were administered AMK (100 mg/kg/day) with or without varying doses of PTX (50 or 100 mg/kg/day) for 28 days.
• Biochemical markers for renal and hepatic function, oxidative stress markers (MDA), and inflammatory cytokines (IL-17) were assessed.
• Histopathological examinations of kidney and liver tissues were performed to evaluate structural damage.

Main Results:

• AMK treatment significantly elevated kidney and liver damage markers, increased oxidative stress, and upregulated IL-17.
• Co-administration of PTX, especially at 100 mg/kg, normalized biochemical parameters and reduced oxidative and inflammatory markers.
• Histopathological analysis revealed that PTX preserved tissue architecture, mitigating AMK-induced damage in a dose-dependent manner.

Conclusions:

• Pentoxifylline demonstrates significant protective effects against amikacin-induced nephrotoxicity and hepatotoxicity in mice.
• PTX effectively mitigates AMK toxicity by restoring antioxidant defenses and suppressing inflammation.
• PTX shows promise as a safe and effective adjunctive therapy to enhance the clinical use of amikacin.