Isovaleramide attenuates ethylene glycol poisoning-induced acute kidney injury and reduces mortality by inhibiting alcohol dehydrogenase activity in rats

Abstract

We explored the potential value of the alcohol dehydrogenase (ADH) inhibitor isovaleramide (ISO) in the treatment of acute ethylene glycol (EG) poisoning-induced acute kidney injury. Sprague–Dawley rats were divided into the control, EG, EG + ISO (10 mg/kg) and EG + ISO (20 mg/kg) groups. It is found that ISO intervention significantly reduced the ADH activity in liver tissue by using visible spectrophotometry, inhibited the in vivo metabolism of EG by using gas chromatography, lowered the levels of toxic metabolites glycolic acid and oxalic acid by using high-performance liquid chromatography and decreased the expression of kidney injury markers serum creatinine (sCr), KIM-1, neutrophil gelatinase-associated lipocalin (NGAL) and liver fatty acid-binding protein (L-FABP) by ELISA. Additionally, Western blotting results showed that ISO down-regulated the expression of apoptotic factors Bax and cleaved caspase-3 in the kidneys and upregulated the expression of antiapoptotic factor Bcl-2. Pizzolato staining and polarized light microscopy results revealed the reduced deposition of calcium oxalate crystals in the kidney tubules. Using haematoxylin and eosin (H&E), periodic acid-Schiff (PAS) and Masson staining, we found attenuated kidney tissue pathological injury. Finally, ISO significantly reduced the mortality rate. In conclusion, ISO has the potential to be a valuable drug for the treatment of EG poisoning-induced acute kidney injury.