Chronic exposure to glyphosate induces cardiac remodeling without functional damage and promotes hepatic morphological and biochemical alterations in rats

AIM: This study aimed to evaluate the effects of chronic inhalation of different glyphosate concentrations on cardiac and hepatic structure and function in rats. METHODS: Forty-two male Wistar rats were randomly divided into three groups control (C, n = 14), exposed to 10 mL of distilled water; low concentration (LC, n = 14), exposed to 3.71 × 10<sup>-3</sup> g of active ingredient per hectare (g.a.i./ha); and high concentration (HC, n = 14), exposed to 9.28 × 10<sup>-3</sup> g.a.i./ha. Exposure occurred via inhalation for 180 days. After the exposure period, echocardiography was performed to assess cardiac function, followed by euthanasia and the collection of heart and liver tissues. Cardiac tissue was subjected to histological analysis, assessment of oxidative stress, inflammation and apoptosis markers, collagen quantification, and fractal dimension analysis. In the liver, histopathological evaluation, fractal dimension analysis, and serum biochemical measurements of ALT and AST were performed. KEY FINDINGS: No cardiac functional impairment was observed. Similarly, anatomical and histomorphometrical assessments showed no structural modifications, and the BAX/BCL-2 ratio remained unchanged. However, the HC group showed increased myocardial collagen, elevated CAT activity, and reduced GST and TNF-α, indicating remodeling with an adaptive antioxidant response. In the liver, the HC group presented histological changes compatible with fibrosis, increased ALT, and decreased AST levels, suggesting hepatic damage, although fractal dimension analysis revealed no significant architectural disruption. SIGNIFICANCE: Chronic inhalation exposure to glyphosate resulted in cardiac remodeling characterized by increased collagen deposition and an adaptive antioxidant response, without functional impairment. In the liver, it led to fibrosis and enzymatic alterations, despite preserved microarchitectural organization.