Neurotoxic effects of nephrotoxic compound diethylene glycol
Autor: | Courtney N. Jamison, Kenneth E. McMartin, Brian Latimer, Hannah G. Mitchell, Robert D. Dayton, Mary P. McKinney |
---|---|
Rok vydání: | 2021 |
Předmět: |
Adult
Male genetic structures Diglycolic acid Kidney Toxicology behavioral disciplines and activities Motor function Organic compound Article Nephrotoxicity 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Animals Humans 030212 general & internal medicine Rats Wistar chemistry.chemical_classification Adulterant Chromatography Chemistry Diethylene glycol 030208 emergency & critical care medicine General Medicine Acute Kidney Injury Rats Solvent Disease Models Animal Ethylene Glycols Neurotoxicity Syndromes sense organs psychological phenomena and processes |
Zdroj: | Clin Toxicol (Phila) |
ISSN: | 1556-9519 1556-3650 |
Popis: | CONTEXT: Diethylene glycol (DEG) is an organic compound found in household products but also as an adulterant in medicines by acting as counterfeit solvent. DEG poisonings have been characterized predominately by acute kidney injury (AKI), but also by delayed neurological sequelae such as decreased reflexes or face and limb weakness. OBJECTIVES: Characterizing the neurological symptoms of DEG poisoning in a subacute animal model would create a clearer picture of overall toxicity and possibly make mechanistic connections between kidney injury and neuropathy. METHODS: Male Wistar-Han rats were orally administered doses of 4 – 6 g/kg DEG every 12 or 24 h and monitored for 7 days. Urine was collected every 12 h and endpoint blood and cerebrospinal fluid (CSF) were collected for a renal plasma panel and total protein estimation, respectively. Motor function tests were conducted before and after treatment. Kidney and brain tissue was harvested for metabolic analysis. RESULTS: Of the 43 animals treated with DEG, 11 developed AKI as confirmed by increased BUN and creatinine levels. Renal and brain DGA accumulation was markedly increased in animals that developed AKI compared to animals without AKI. The total protein content in CSF in animals with kidney injury was markedly elevated compared to control and to treated animals without AKI. Significant decreases in forelimb grip strength and decreases in locomotor and rearing activity were observed in animals with AKI compared to control and to animals without AKI. DISCUSSION: Repeated dosing with DEG in an animal model produced nephrotoxic effects like those in studies with acute DEG administration. The decrease in motor function and increase in CSF protein were only present in animals that developed AKI. CONCLUSIONS: These studies show development of neurotoxicity in this DEG animal model and suggest that neurological symptoms are observed only when DGA accumulation and kidney injury also occur. |
Databáze: | OpenAIRE |
Externí odkaz: | |
Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |