Chronic effects of methamidophos, endosulfan and carbamate pollutants on multi‐organic uptake of Gallium‐67 citrate in mice

Abstract

Organic‐persistent pollutants (POP’s, e.g., herbicides, pesticides) are chemicals used in multiple sectors of daily life. However, chronic overexposure of these endocrine disruptors represents a severe problem in public health worldwide since it is a risk factor for inflammation linked diseases. In nuclear medicine, 67Ga‐Ci is a radiopharmaceutical used for scanning deep neoplastic or inflammatory lesions difficult to diagnose.ObjectiveEvaluate the multi‐organic uptake of 67Ga‐Ci as a possible inflammatory biomarker in POP’s exposure.MethodsThe study used four CD1 male mice groups (n=4; 10 wk‐age); I‐control (CT); and animals that received daily low lethal doses of pollutants for 30d orally; II‐methamidophos (organophosphate compound) (M) (1 mg/kg/d); II‐endosulfan (organochlorine compound) (E) (1 mg/kg/d); and III‐carbamate (C) (10 mg/kg/d). At the end of the study, 180.3±15.1 micro‐Curies (μCi) of 67Ga‐Ci were injected into each mouse intraperitoneally. 24 hr. Later were sacrificed; blood was obtained by direct cardiac puncture. The organs were removed, washed, weighed, and placed in tubes for radioactivity quantification in a Counter Well. The absorption (counts per minute) of 67Ga‐Ci was corrected by physical decomposition (decrease in radioactivity concerning time). Absorption was normalized by organs mass (g) and total activity administered in (μCi) to obtain % absorption activity [(μCi/g)/μCi‐adm].ResultsRegarding control (CT), the compartments with significant increase of 67Ga‐Ci uptake or similar trend were: Blood (CT) 0.3±0.002 vs. (M) 0.08±0.01*, (C) 0.057±0.01, (E) 0.06±0.01; Heart (CT) 0.053±0.01 vs. (M) 0.1±0.02*, (C) 0.09±0.01, (E) 0.1±0.013; and Kidney (CT) 0.19±0.02 vs. (M) 0.25±0.068, (C) 0.22±0.014, (E) 0.2±0.001. Contrary, the organs that presented less 67Ga‐Ci uptake were: Liver (CT) 0.08±0.008 vs.(M) 0.06±0.007, (C) 0.06±0.009, (E) 0.047±0.009*; Lung (CT) 0.314±0.08 vs. (M) 0.178±0.022*, (C) 0.151±0.012*, (E) 0.183±0.03*; Pancreas (CT) 0.067±0.044 vs. (M) 0.23±0.06*, (C) 0.234±0.015*, (E) 0.36±0.02*; Gonads (CT) 0.38±0.03* vs. (M) 0.135±0.017*, (C) 0.113±0.01*, (E) 0.1±0.001*; and Spleen (CT) 1.12±0.07 vs. (M) 1.01±0.046, (C) 0.306±0.04*, (E) 0.48±004*. 67Ga‐Ci is an iron analog; therefore, the increase‐decrease could indicate that the inflammatory processes or the metabolic iron behavior may not coincide. In this study, the increase of 67Ga‐Ci uptake could indicate specific organ inflammation or greater iron requirements due to a severe deficiency; contrary, the decreased uptake could be the result of the anti‐inflammatory response, tissue iron overload or alterations in it is transport mechanisms. The chronic dose‐dependent effects of POP’s may have divergent responses respect to 67Ga‐Ci utility since chronic inflammatory processes could cause iron deficiency. Additional biochemical and molecular studies are required to determine if both responses are consistent.Support or Funding Informationcollaborative funding