# Class III Alcohol Dehydrogenase Modulates Renal Parietal Epithelial Cell Transformation During Chronic Alcohol Consumption in Mice

## TL;DR

This study shows that Class III alcohol dehydrogenase in the kidney helps regulate testosterone levels and protects against kidney damage during chronic alcohol consumption in mice.

## Contribution

The study reveals a novel role of ADH3 in testosterone metabolism and its impact on kidney health during chronic alcohol use.

## Key findings

- ADH3-deficient mice showed increased parietal epithelial cells even without alcohol consumption.
- Chronic alcohol consumption elevated testosterone levels and PECs in wild-type mice.
- ADH3 appears to protect kidney structure by metabolizing testosterone, which is disrupted by alcohol.

## Abstract

Class III alcohol dehydrogenase (ADH3), primarily localized in the liver and kidney, contributes to alcohol metabolism during chronic alcohol consumption (CAC). However, its role in kidney function remains unclear. This study investigated renal morphological changes associated with ADH3-mediated alcohol metabolism. Nine-week-old male wild-type (WT) and ADH3-deficient (Adh3-/-) mice were administered 10% ethanol for 1 month. Histological analyses were performed using periodic acid–Schiff (PAS) staining and electron microscopy. Serum biochemical parameters were also assessed. In WT mice, CAC induced an increase in cuboidal parietal epithelial cells (PECs) in Bowman’s capsule, along with elevated testosterone levels in both serum and urine. Adh3-/- mice showed increased PECs even in the control group, with similarly elevated serum testosterone in both control and ethanol-treated groups. These findings suggest that ADH3 is involved in testosterone metabolism, and that that metabolism is suppressed by CAC because ADH3 shifts toward ethanol metabolism. The resulting testosterone elevation may contribute to PEC proliferation. An increase in PECs observed even in Adh3-/- control mice may also be caused by the lack of testosterone metabolism via ADH3. Thus, renal ADH3 may protect kidney structure through testosterone metabolism, but its role may be disturbed by CAC. This study highlights the role of ADH3 in the relationship between physiological steroid metabolism and alcoholic pathological abnormality in the kidney.