Effects of genistein on inflammation responses in the heart of the rats with cigarette smoke and airway lipopolysaccharide exposure

Abstract

Cigarette smoke and lung infection are major risk factors of heart diseases, due to the systemic inflammation in the circulation and/or the spillover of inflammatory factors from the lungs to the heart. Clinical studies suggest that there is a link between heart diseases and lung disorders caused by cigarette smoke or lung infection; and cigarette smoke might enhance or inhibit the inflammatory responses resulted from lung infection. Genistein, a product present in soy, was reported to be cardio-protective and anti-inflammatory. Thus, the aim of the present study was to investigate the effect of genistein on inflammatory responses in the heart of the rats with cigarette smoke and airway lipopolysaccharide exposure.

In the present study, rats were treated with or without genistein by gavage for 8 weeks. During the treatment, they were exposed to cigarette smoke daily for one hour or intratracheally challenged with bacterial endotoxin lipopolysaccharide (LPS) twice (in week 5 and 7), alone or in combination, to mimic the condition of inflammatory responses triggered by cigarette smoke or infection. To examine the degree of cardiac inflammatory responses, the inflammatory mediators [cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1)] in the heart tissues of rats were measured with enzyme-linked immune-sorbent assays. Moreover, the activities of nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinases (MAPKs) [major molecules involved in inflammatory responses] were measured with Western blotting by detecting the levels of phosphorylated (activated) and total proteins in the pathway.

The combined treatment of cigarette smoke and LPS resulted in increased levels of IL-6 and MCP-1 inthe heart when comparing with control group, while the levels of other cytokines were comparable in the groups treated without or with cigarette smoke or LPS exposure. The levels of phosphorylation of NF-κB proteins and MAPKs were not significantly different among the different treatment groups. In rats treated with genistein, the increased IL-6 and MCP-1 levels in the heart due to the combined effect of cigarette smoke and airway LPS exposure were smaller. The findings suggest that, under the present experimental conditions, airway exposure to bacterial endotoxin or long-term cigarette smoke exposure alone does not induce significant inflammatory responses in the heart. On the other hand, cigarette smoking may enhance the detrimental effect of bacterial endotoxin. Genistein seems to have certain degree of protective effect against the induction of inflammatory responses in the heart by preventing the release of IL-6 and MCP-1 by cigarette smoke with LPS challenge.