Journal of Alcoholism & Drug Dependence

Journal of Alcoholism & Drug Dependence
Open Access

ISSN: 2329-6488


Role of Class III Alcohol Dehydrogenase (ADH3) in Renal Pathological Changes Induced by Chronic Alcohol Consumption in Mice

Midori Katsuyama*, Takahisa Okuda, Yoshihiro Sasaki, Masamichi Ishizaki, Kentaro Wada, Motoyo Maruyama, Toshio Akimoto, Youkichi Ohno and Takeshi Haseba

Aims: Our study investigated ADH3 role in renal pathological changes induced by chronic alcohol consumption (CAC).

Methods: Nine-week-old malewild-type (WT) and ADH3-deficient (Adh3−/−) mice were administered 10% ethanol solution for 1 month. Renal histological and ultrastructural analyses were performed by light microscopy on periodic acid–Schiff (PAS) staining and electron microscopy. The tissue ADH3 localization was examined by immunohistochemistry using a specific antibody against mouse ADH3. Urine and serum biochemical analyses were performed.

Results: The PAS-stained microvilli in the proximal tubules were significantly low in the WT mice after CAC (WT (E)) as compared to the Adh3−/− mice (Adh3−/− (E)). The electron microscopy revealed vacuolization, nuclear apoptosis, mitochondrial decay, loss of microvilli in the proximal tubulesin the WT (E) mice, foot process effacement and epithelial cells apoptosis in the glomeruli. In the Adh3−/− (E) mice, loss of PAS staining in the proximal tubules and significant ultrastructure changes were not observed, except for mitochondrial decay in the proximal tubules. ADH3 was localized in proximal tubules, consistent with the pathomorphological changes characteristic of the site in the WT (E) mice. CAC increased urinary albumin and total protein levels CAC in the WT mice, but not in the Adh3−/− mice. These biochemical data demonstrate increased glomerular permeability in the WT (E) mice, foot process effacement and apoptosis of epithelial cells in the glomeruli.

Conclusions: ADH3 causes renal proximal tubules pathological changes by metabolizing alcohol in this site and increased glomerular permeability during CAC. Thus, ADH3 exacerbates alcoholic kidney disorders.

Published Date: 2021-04-22; Received Date: 2021-03-26