Aminoguanidine attenuates arsenic-induced hepatic oxidative stress: Dose-dependent effects in a mouse model

TL;DR

Aminoguanidine protects mouse livers from arsenic damage, with the best results at a 50 mg/kg dose.

Contribution

Demonstrates aminoguanidine's dose-dependent hepatoprotective effects against arsenic-induced oxidative stress in mice.

Findings

Aminoguanidine at 50 mg/kg/day showed optimal liver protection and reduced oxidative stress markers.

Higher aminoguanidine doses (100 mg/kg/day) were less effective in protecting liver histology.

Aminoguanidine improved plasma antioxidant capacity at both tested doses.

Abstract

Arsenic exposure through environmental contamination poses significant public health concerns via oxidative stress-mediated toxicity. While aminoguanidine (AG) demonstrates antioxidant properties, its protective effects against arsenic-induced hepatotoxicity remain unexplored.

Male mice (n = 32) were randomized into four groups (n = 8 per group): control (distilled water), arsenic (50 ppm sodium arsenite in drinking water), and two treatment groups receiving arsenic plus aminoguanidine (50 or 100 mg/kg/day, i.p.) for 28 days. Hepatic oxidative stress markers, plasma antioxidant capacity, and liver histopathology were evaluated.

Arsenic exposure induced significant liver histopathological changes (grade +2) and oxidative damage. AG treatment at 50 mg/kg/day showed optimal protective effects, with some samples displaying normal hepatic structure (grade 0) and others showing minimal changes (grade +1). This dose effectively reduced lipid peroxidation and protein carbonylation in liver tissue. The higher AG dose (100 mg/kg/day) demonstrated less protective effect, though it significantly improved plasma antioxidant capacity compared to the arsenic group.

Aminoguanidine demonstrates dose-dependent hepatoprotective effects against arsenic-induced oxidative damage, with 50 mg/kg/day showing optimal efficacy. Further investigation of lower doses over extended periods is warranted to establish its therapeutic potential in arsenic toxicity.

•Aminoguanidine provides dose-dependent protection against arsenic-induced liver damage.•50 mg/kg optimal dose: 62.5 % normal histology, reduced oxidative stress markers.•Inverted dose-response: 100 mg/kg less effective than 50 mg/kg.•Multiple protective mechanisms: histological preservation and biochemical improvement.•Novel therapeutic approach for arsenic toxicity with defined optimal window.

Aminoguanidine provides dose-dependent protection against arsenic-induced liver damage.

50 mg/kg optimal dose: 62.5 % normal histology, reduced oxidative stress markers.

Inverted dose-response: 100 mg/kg less effective than 50 mg/kg.

Multiple protective mechanisms: histological preservation and biochemical improvement.

Novel therapeutic approach for arsenic toxicity with defined optimal window.

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