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Chem Biol Interact. 2019 Jun 4. pii: S0009-2797(19)30345-X. doi: 10.1016/j.cbi.2019.06.002. [Epub ahead of print]

Contrast media (meglumine diatrizoate) aggravates renal inflammation, oxidative DNA damage and apoptosis in diabetic rats which is restored by sulforaphane through Nrf2/HO-1 reactivation.

Author information

1
Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt; Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA. Electronic address: sakhaleel@azhar.edu.eg.
2
Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
3
Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt; Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
4
Department of Pathology, College of Medicine, Al-Azhar University, Cairo, Egypt.

Abstract

Diabetes mellitus is an independent risk factor for renal impairment in patients exposed to contrast media. It doubles the risk and decreases survival rate of contrast induced nephropathy (CIN). Sulforaphane has antioxidant properties via Nrf2 activation. The interaction of diabetes and/or sulforaphane with contrast media on Nrf2 regulation is not yet understood. Herein, diabetes was induced by a single intra-peritoneal injection of streptozotocin. Animals were then divided into five groups; control non-diabetic group; diabetic group; diabetic/sulforaphane group; diabetic/CIN group; diabetic/CIN/sulforaphane group. Animals were assessed 24 h after CIN induction. Sulforaphane improved the impaired nephrotoxicity parameters, histopathological features, and oxidative stress markers induced by contrast media (meglumine diatrizoate) in diabetic rats. Immunofluorescence detection revealed increased Nrf2 expression in kidney sections after sulforaphane pretreatment. Moreover, gene expression of Nrf2 and HO-1 were up-regulated, while IL-6 and caspase3 were down-regulated in kidney tissues of animals pretreated with sulforaphane. In NRK-52E cells, sulforaphane pretreatment significantly ameliorated the cytotoxicity of meglumine diatrizoate. However, silencing Nrf2 using small interfering RNA (siRNA) abolished the cytoprotective effects of sulforaphane. Collectively, the results of this study suggest that Nrf2/HO-1 pathway has a protective role against CIN and support the clinical implication of Nrf2 activators, such as sulforaphane, in CIN particularly in diabetic patients.

KEYWORDS:

Contrast induced nephropathy; Diabetes; Nrf2; Oxidative stress; Sulforaphane

PMID:
31173751
DOI:
10.1016/j.cbi.2019.06.002

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