Article ; Online: Sulforaphane, an Nrf-2 Agonist, Modulates Oxidative Stress and Inflammation in a Rat Model of Cuprizone-Induced Cardiotoxicity and Hepatotoxicity.
2023 Volume 23, Issue 1, Page(s) 46–60
Abstract: Cuprizone (CPZ) is a neurotoxic agent that is used to induce demyelination and neurotoxicity in rats. This study aimed to investigate the protective potential of sulforaphane (SF), nuclear factor E2 related factor (Nrf-2) activator, against CPZ-induced ... ...
| Abstract | Cuprizone (CPZ) is a neurotoxic agent that is used to induce demyelination and neurotoxicity in rats. This study aimed to investigate the protective potential of sulforaphane (SF), nuclear factor E2 related factor (Nrf-2) activator, against CPZ-induced cardiotoxicity and hepatotoxicity. Male adult Wistar rats (n = 18) were fed with a regular diet or a CPZ-contained diet (0.2%) for four weeks. The rats were divided into three groups (n = 6): negative control rats, CPZ-exposed rats, and CPZ + SF treated rats. SF was intraperitoneally administrated (2 mg/kg/day) for two weeks. The anti-inflammatory and anti-oxidative functions of SF were investigated biochemically, histologically, and immunohistochemically. CPZ increased serum levels of cardiac troponin 1 (CTn1), aspartate amino transaminase (AST), alanine amino transaminase (ALT), and alkaline phosphatase (ALP). In addition, serum levels of inflammatory interferon-gamma (IFN-γ), and pro-inflammatory interleukin 1β (IL-1β) were significantly elevated. Moreover, CPZ administration provoked oxidative stress as manifested by declined serum levels of total antioxidant capacity (TAC), as well as, stimulated lipid peroxidation and decreased catalase activities in both cardiac and hepatic tissues. SF treatment reversed all these biochemical alterations through exerting anti-oxidative and anti-inflammatory activities, and this was supported by histopathological investigations in both cardiac and hepatic tissues. This SF-triggered modulation of oxidative stress and inflammation is strongly associated with Nrf-2 activation, as evidenced by activated immunoexpression in both cardiac and hepatic tissues. This highlights the cardioprotective and hepatoprotective activities of SF via Nrf-2 activation and enhancing catalase function. |
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| MeSH term(s) | Animals ; Male ; Rats ; Anti-Inflammatory Agents/therapeutic use ; Antioxidants/metabolism ; Cardiotoxicity/metabolism ; Catalase/metabolism ; Chemical and Drug Induced Liver Injury/etiology ; Chemical and Drug Induced Liver Injury/prevention & control ; Chemical and Drug Induced Liver Injury/metabolism ; Cuprizone/metabolism ; Cuprizone/pharmacology ; Cuprizone/therapeutic use ; Inflammation/chemically induced ; Inflammation/metabolism ; Liver/pathology ; Oxidative Stress ; Rats, Wistar |
| Chemical Substances | Anti-Inflammatory Agents ; Antioxidants ; Catalase (EC 1.11.1.6) ; Cuprizone (5N16U7E0AO) ; sulforaphane (GA49J4310U) ; Nfe2l2 protein, rat |
| Language | English |
| Publishing date | 2023-01-17 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 2036765-X |
| ISSN | 1559-0259 ; 1530-7905 |
| ISSN (online) | 1559-0259 |
| ISSN | 1530-7905 |
| DOI | 10.1007/s12012-022-09776-0 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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