Effects of inflammatory responses, apoptosis, and STAT3/NF-κB- and Nrf2-mediated oxidative stress on benign prostatic hyperplasia induced by a high-fat diet

Abstract

This study determined whether or not benign prostatic hyperplasia (BPH) induced by a high-fat diet (HFD) is involved in inflammatory responses, apoptosis, and the signal transducer and activator of transcription (STAT3)/nuclear factor-kappa B (NF-κB)- and nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated oxidative stress pathways. Forty rats were divided into four groups: control; HFD; testosterone; and HFD+testosterone. Hematoxylin and eosin (HE) staining was used to assess histologic changes. An enzyme-linked immunosorbent assay and Western blot analysis were used to detect levels of related proteins. Compared with the control group, the prostate levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), transforming growth factor-β1 (TGF-β1), and monocyte chemotactic protein-1 (MCP-1) were significantly increased, while the levels of glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione (GSH), and superoxide dismutase (SOD) were decreased. The TNF-κB, Bcl-2, and caspase-3 levels were increased, while the Bax level was markedly decreased. The cytoplasmic expression of STAT3 and NF-κB was increased, while the nuclear expression of Nrf2 was markedly decreased compared with the control group. In summary, our results demonstrated that a long-term HFD might cause changes in inflammatory responses, apoptosis, and oxidative stress, thus contributing to prostatic hyperplasia. The underlying mechanisms might be related to the STAT3/NF-κB- and Nrf2-mediated oxidative stress pathway.

GV1001 interacts with androgen receptor to inhibit prostate cell proliferation in benign prostatic hyperplasia by regulating expression of molecules related to epithelial-mesenchymal transition

“…Here, we report a novel function of GV1001: it effectively suppresses proliferation of prostatic epithelial cell and stromal cells in vitro and reduces enlargement of the prostate in an experimental mouse model of BPH. In contrast to most in vivo experiments regarding BPH, which were performed in animal models subcutaneously injected with testosterone after castration [ 29 , 30 ], we examined the therapeutic effects and related mechanisms of GV1001 in a testosterone-induced BPH model in which mice were implanted with a micro-osmotic pump to allow spontaneous release of testosterone in vivo ( Supplementary Figure 3 ). There was no effect on BPH in mice treated with GV1001 or finasteride alone ( Supplementary Figure 4 ).…”

Phloretin Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Regulating the Inflammatory Response, Oxidative Stress and Apoptosis

“…This may have caused excessive production of ROS and OS, resulting in a rise in cases of BPH. Similar to our experiment, the impact of a high-fat diet was investigated [ 32 ]. It could increase levels of IL-6 and COX-2, thereby promoting the inflammatory process.…”

Physical Exercise Mitigates the Disturbs Caused in Ventral Prostate by High Fat Diet, Clarifying the Role of PPAR-Alpha

“…The increased expression of IL-6, an NF-kB inducible gene, is an autocrine growth factor for prostate cancer cells. However, the increase in the in ammatory response to an HFD occurs due to the increase in the expression of MCP-1, IL-6,and TNF-and inhibits the anti-in ammatory effect of GR 48 . The absence of PPAR did not interfere with the expression of GR, however, the HFD up-regulated GR in the prostate.…”