#3577 Peritoneal infusion of microplastics induces over-expression of GDF-15 in kidney and heart in mice

Abstract Background and Aims There is growing concern regarding the potential impact of microplastics (MPs) on human health. Patients with chronic kidney disease (CKD) undergoing peritoneal dialysis may be particularly vulnerable to exposure to these particles. Recent findings have demonstrated the presence of microplastics in human urine and kidney tissue, highlighting the potential toxicity of these substances. In light of these concerns, we aimed to investigate the effects of microplastics on kidney and heart tissues, with a particular focus on the expression of GDF-15. GDF-15 (growth differentiation factor 15) is a cytokine involved in various biological processes, including the inhibition of apoptosis and the modulation of inflammation under several pathological conditions. As a member of the TGF-beta family, GDF-15 is expressed in numerous tissues and plays a key role in oxidative stress and mitochondrial dysfunction. Elevated levels of GDF-15 have been associated with an increased risk of mortality, the onset of CKD, and its progression in individuals with renal impairment. In a recent proteomic study (data not yet published), we identified GDF-15 as a potential biomarker for microplastic exposure in kidney tubular cells. Method Eight-week-old male BL/6 mice were housed in standard cages with ad libitum access to chow and water. Green Fluorescent Polymer Microspheres (FMG, maximum excitation wavelength 515 nm), with a diameter range of 1–5 μm, were purchased from Cospheric LLC (Santa Barbara, USA). The mice were administered 0.25 mg of FMG, diluted in deionized water (total volume of 150 μl), via intraperitoneal injection. This treatment was repeated three times a week for a duration of four weeks. No acute adverse effects were observed following the administrations. Urine samples were collected at various time points until sacrifice. Mice that received FMG treatment, along with one untreated control mouse, were sacrificed 30 days after the first dose to collect blood serum, and kidney, heart, liver, and spleen tissues. Immunohistochemical staining for GDF-15 was performed on kidney and heart tissue sections. Results Our analysis revealed the deposition of microplastics in both kidney and heart tissues following peritoneal administration. GDF-15 expression was significantly increased in the heart (P = 0.02) and kidney (P < 0.0001) tissues (Figs 1 and 2). Conclusion Our findings demonstrate that microplastics, when administered via the peritoneal route, are detectable in target organs such as the kidney and heart. Furthermore, exposure to microplastics leads to a significant overexpression of GDF-15, a cytokine that may serve as a potential biomarker for inflammation in these tissues. This study provides valuable insights into the toxicological effects of microplastic exposure on organ systems and underscores the need for further investigation into the role of GDF-15 as a potential marker of exposure-related inflammation.