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Updated: Jul 4, 2026
Modeling Hypoxia/Reoxygenation Injury in Proximal Tubular Epithelial Cells
Published on: November 21, 2025
Glyoxylate induces renal tubular cell injury and microstructural changes in experimental mouse
Masahito Hirose1, Keiichi Tozawa, Atsushi Okada
1Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-Cho, Mizuho-ku, Nagoya City, Aichi, 467-8601, Japan.
Abstract:
Crystal formation in mice could not be induced either by the administration of ethylene glycol or by glycolate. To clarify the reasons for the difference among these oxalate precursors in mice, we studied renal tubular epithelial injury by immunohistochemical staining of oxidative stress and observing microstructures. Daily intra-abdominal injection of saline solution [10 ml/(kg day)], ethylene glycol[(48.3 mmol/(kg day)], glycolate [1.31 mmol/(kg day)], and glyoxylate [1.35 mmol/(kg day)] into C57BL/6 male mice (8 weeks) was performed for 7 days. Immunohistochemical staining of superoxide dismutase (SOD) and malondialdehyde (MDA), and transmission electron microscopy (TEM) of renal tubular epithelial cells were performed to observe oxidative stress and morphological changes, respectively. Decreased SOD and increased MDA were shown only in glyoxylate-treated mouse kidneys. The TEM study with glyoxylate-treated mouse kidneys demonstrated that the internal structure of mitochondria in renal tubular cells underwent destruction and vacuolization, and microvilli density decreased. These changes in renal tubular cells were located in the crystal-forming area. However, such changes were not detected in the other groups. Each precursor of oxalate induces different changes in renal epithelial cells regarding oxidative stress and the microstructural changes. It is suggested that calcium oxalate crystal formation requires cell injury and morphological changes of renal epithelial tubular cells induced by glyoxylate administration in the mouse kidney.
Insights
Glyoxylate, but not ethylene glycol or glycolate, induces kidney cell injury and oxidative stress in mice, suggesting it is necessary for calcium oxalate crystal formation. This research clarifies oxalate precursor differences in mice.
Area of Science:
- Nephrology
- Toxicology
- Cell Biology
Background:
- Calcium oxalate crystal formation is a significant cause of kidney stones.
- The specific mechanisms and precursors involved in initiating crystal formation in vivo are not fully understood.
- Differences in the effects of oxalate precursors on renal cells require further investigation.
Purpose of the Study:
- To investigate the differential effects of ethylene glycol, glycolate, and glyoxylate on renal tubular epithelial cells in mice.
- To elucidate the role of oxidative stress and cellular microstructural changes in calcium oxalate crystal formation.
- To clarify why only certain oxalate precursors induce crystal formation in mice.
Main Methods:
- Administration of ethylene glycol, glycolate, and glyoxylate to C57BL/6 male mice for 7 days.
- Immunohistochemical staining for oxidative stress markers: superoxide dismutase (SOD) and malondialdehyde (MDA).
- Transmission electron microscopy (TEM) to assess morphological changes in renal tubular epithelial cells.
Main Results:
- Glyoxylate administration led to decreased SOD and increased MDA, indicating significant oxidative stress.
- TEM revealed mitochondrial destruction, vacuolization, and decreased microvilli density in renal tubular cells of glyoxylate-treated mice.
- No significant oxidative stress or microstructural damage was observed in mice treated with ethylene glycol or glycolate.
Conclusions:
- Glyoxylate induces distinct renal tubular epithelial cell injury, characterized by oxidative stress and morphological alterations.
- These glyoxylate-induced cellular changes are localized to crystal-forming areas in the kidney.
- The findings suggest that cell injury and morphological changes mediated by glyoxylate are prerequisites for calcium oxalate crystal formation in the mouse kidney.
