| Autor: |
N, Jamison Courtney, K, Cuevas-Ocampo Areli, B, Flowers Ashley, W, Nam Hyung, D, Dayton Robert, P, McKinney Mary, G, Mitchell Hannah, S, Fitzgerald Joseph, E, Steib Mattie, R, Toups Colton, E, McMartin Kenneth |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
NeuroToxicology. 91:200-210 |
| ISSN: |
0161-813X |
| DOI: |
10.1016/j.neuro.2022.05.015 |
| Popis: |
Diethylene glycol (DEG) is an organic compound that has been found as an adulterant in consumer products as a counterfeit glycerin. Diethylene glycol is metabolized to two primary metabolites: 2-hydroxyethoxyacetic acid (2-HEAA) and diglycolic acid (DGA), the latter shown to accumulate in the kidney and cause dose-dependent cell necrosis. DEG poisonings are characterized predominately by acute kidney injury (AKI) but have also produced delayed neurological sequelae such as sensorimotor neuropathy. To better understand these effects, Wistar-Han rats were orally administered a water control or doses of 4 g/kg-6 g/kg DEG every 12 or 24 h for 7 days, with kidney, brain, and spinal cord tissue collected for histopathological analysis. This dosing paradigm resulted in approximately 25 % of the DEG-treated animals developing AKI and also neurotoxicity (sensorimotor dysfunction and elevated cerebrospinal fluid (CSF) protein). Kidney pathology included a severe, diffuse acute kidney tubular necrosis predominantly affecting proximal convoluted tubules. Scattered birefringent crystals consistent with calcium oxalate monohydrate were also found in the proximal tubule of animals with AKI. Demyelination in the dorsal and lateral white matter regions of the cervical, thoracic, and lumbar areas of the spinal cord of a DEG-treated animal with AKI was documented, establishing the neuropathology in DEG-treated animals that developed neurotoxicity. There were significant changes in amino acid concentrations in the CSF that may reflect the neurotoxicity of DEG, specifically glutamate and glutamine, but with no ammonia change. These studies characterized the pathologic aspects of the neurotoxicity in a DEG repeat-dose model. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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Full Text from ScienceDirect