Cytochrome P450-2E1 is involved in aging-related kidney damage in mice through increased nitroxidative stress. (November 2017)

• Record Type: Journal Article
• Authors: Abdelmegeed, Mohamed A.; Choi, Youngshim; Ha, Seung-Kwoon; Song, Byoung-Joon
• Is Part Of: Food and chemical toxicology. Volume 109:Part 1(2017)
• Page Start: 48
• Page End: 59
• Publication Date: 2017-11
• Subjects: Kidney -- Aging -- CYP2E1 -- Apoptosis -- Fibrosis -- Oxidative stress; APAP acetaminophen -- ATP5B ATP synthase subunit Beta -- CAT catalase -- Cytochrome P450 CYP -- DNPH dinitrophenylhydrazine -- GCLC glutamate-cysteine ligase catalytic subunit -- GCLM glutamate-cysteine ligase modifier subunit -- GSH glutathione -- Gpx glutathione peroxidase -- HO-1 heme oxygenase-1 -- H2O2 hydrogen peroxide -- IHC immunohistochemistry -- iNOS inducible nitric oxide synthase -- NADPH oxidase nicotinamide adenine dinucleotide phosphate oxidase -- NO nitric oxide -- 3-NT 3-nitrotyrosine -- PAS periodic acid-Schiff -- RNS reactive nitrogen species -- ROS reactive oxygen species -- SOD superoxide dismutase -- TNFα tumor necrosis factor-α -- TUNEL terminal deoxynucleotidyl transferase dUTP nick end labeling -- WT wild-type; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2017.08.022
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: The aim of this study was to investigate the role of cytochrome P450-2E1 (CYP2E1) in aging-dependent kidney damage since it is poorly understood. Young (7 weeks) and aged female (16–17 months old) wild-type (WT) and Cyp2e 1-null mice were used. Kidney histology showed that aged WT mice exhibited typical signs of kidney aging such as cell vacuolation, inflammatory cell infiltration, cellular apoptosis, glomerulonephropathy, and fibrosis, along with significantly elevated levels of renal TNF-α and serum creatinine than all other groups. Furthermore, the highest levels of renal hydrogen peroxide, protein carbonylation and nitration were observed in aged WT mice. These increases in the aged WT mice were accompanied by increased levels of iNOS and mitochondrial nitroxidative stress through altered amounts and activities of the mitochondrial complex proteins and significantly reduced levels of the antioxidant glutathione (GSH). In contrast, the aged Cyp2e1 -null mice exhibited significantly higher antioxidant capacity with elevated heme oxygenase-1 and catalase activities compared to all other groups, while maintaining normal GSH levels with significantly less mitochondrial nitroxidative stress compared to the aged WT mice. Thus, CYP2E1 is important in causing aging-related kidney damage most likely through increasing nitroxidative stress and that CYP2E1 could be a potential target in preventing aging-related kidney diseases. Highlights: The role of CYP2E1 in aging-related kidney damage is largely unknown. Young and aged female wild-type (WT) and Cyp2e 1-null mice were evaluated. Aged WT mice exhibited highest levels of inflammation, nitroxidative stress, apoptosis, and fibrosis. Cyp2e1 -null mice were resistant to aging-related kidney damage partly due to high levels of antioxidant capacity. CYP2E1 is important in mediating aging-related kidney damage.