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Cytochrome P450-2E1 is involved in aging-related kidney damage in mice through increased nitroxidative stress

Mohamed A Abdelmegeed1, Youngshim Choi1, Seung-Kwoon Ha1

  • 1Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
|August 28, 2017
PubMed

Insights

Cytochrome P450-2E1 (CYP2E1) contributes to kidney damage in aging, likely by increasing oxidative stress. Eliminating CYP2E1 may protect against age-related kidney disease.

Area of Science:

  • Biochemistry
  • Gerontology
  • Nephrology

Background:

  • Aging is associated with kidney damage, but the underlying mechanisms are not fully understood.
  • Cytochrome P450-2E1 (CYP2E1) is implicated in cellular damage, but its role in aging-dependent kidney dysfunction requires investigation.

Purpose of the Study:

  • To investigate the role of CYP2E1 in aging-related kidney damage.
  • To determine if CYP2E1 contributes to oxidative stress and kidney dysfunction in aged mice.

Main Methods:

  • Comparison of kidney histology, oxidative stress markers (hydrogen peroxide, protein carbonylation, nitration), inflammatory markers (TNF-α), and kidney function (serum creatinine) in young and aged wild-type (WT) and Cyp2e1-null mice.
  • Assessment of mitochondrial function and antioxidant capacity, including glutathione (GSH) levels and specific enzyme activities.

Main Results:

  • Aged WT mice showed significant kidney aging signs, elevated TNF-α and creatinine, increased oxidative and nitroxidative stress markers, and reduced GSH compared to other groups.
  • Aged Cyp2e1-null mice exhibited enhanced antioxidant capacity (heme oxygenase-1, catalase), normal GSH levels, and reduced mitochondrial nitroxidative stress compared to aged WT mice.

Conclusions:

  • CYP2E1 plays a critical role in promoting aging-related kidney damage, primarily through the exacerbation of nitroxidative stress.
  • CYP2E1 inhibition represents a potential therapeutic target for preventing or mitigating age-related kidney diseases.
Keywords:
AgingApoptosisCYP2E1FibrosisKidneyOxidative stress

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