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Activation of nuclear factor erythroid 2‐related factor 2 ( N rf2) and N rf‐2‐dependent genes by ischaemic pre‐conditioning and post‐conditioning: new adaptive endogenous protective responses against renal ischaemia/reperfusion injury
Author(s) -
Shokeir A. A.,
Hussein A. M.,
Barakat N.,
Abdelaziz A.,
Elgarba M.,
Awadalla A.
Publication year - 2014
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12164
Subject(s) - creatinine , proinflammatory cytokine , chemistry , medicine , kidney , blood urea nitrogen , endocrinology , endogeny , tumor necrosis factor alpha , microbiology and biotechnology , biology , inflammation
Abstract Aim To investigate the impact of ischaemic pre‐conditioning ( I pre) and post‐conditioning ( I post) on expression of nuclear factor erythroid 2‐related factor 2 ( N rf2) gene and its dependent genes, haem oxygenase‐1 ( HO ‐1) and NADPH ‐quinone oxidoreductase‐1 ( NQO ‐1); inflammatory cytokines TNF ‐α, IL 1β and ICAM ‐1; and apoptotic markers such as caspase‐3 in renal ischaemia/reperfusion ( I / R ) injury. Methods One hundred and fifty male S prague D awley rats were classified into five groups (each consisted of 30 rats): sham, control ( I / R ), I pre + I / R , I pre without I / R and I post + I / R . Serum creatinine and blood urea nitrogen ( BUN ) were measured at 2, 24 and 48 h after ischaemia. In kidney tissues, m RNA of N rf2, HO ‐1, NQO ‐1, TNF ‐α, IL ‐1β and ICAM ‐1 and immunohistochemical expression of N rf2 and caspase‐3 were assessed. Results Serum creatinine and BUN improved significantly in P re + I / R group; however, they did not show any significant improvement in P ost + I / R group. Also, I pre‐ I / R group showed non‐significant change in serum creatinine and BUN . The expression of N rf2, HO ‐1 and NQO ‐1 is increased significantly in P re + I / R and P re − I / R groups, while the enhancement in P ost + I / R group was non‐significant. Moreover, the expression of proinflammatory cytokines ( TNF ‐α, IL ‐1 and ICAM ‐1) and apoptotic (caspase‐3) markers showed high significant attenuation in P re + I / R group, but slight significant attenuation in P re + I / R group. Conclusion The renoprotective action of I pre might include early activation and enhanced expression of N rf2 gene and its dependent antioxidant genes, HO ‐1 and NOQ 1, as endogenous adaptive renoprotective genes, as well as reduction in TNF ‐α, IL ‐1β, ICAM ‐1 and caspase‐3.