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.

Keywords: apoptosis; benign prostatic hyperplasia; high-fat diet; inflammatory responses; oxidative stress.

Figure 1

Histologic changes in rat prostate (HE stain, ×40). (A) Control group; (B) HFD group; (C) Testosterone group; (D) HFD+testosterone group.

Figure 2

Effects of a long-term HFD on prostatic COX-2, iNOS, TNF-α, IL-6, TGF-β1, MCP-1, MDA, SOD, GSH-Px, GR, and GSH (A–K) levels by ELISA. Results are representative of three independent experiments. ^##p<0.01 and ^#p<0.05, compared with the control group; *p<0.05 compared with the testosterone group.

Figure 3

Effects of a long-term HFD on the expression of NF-κB, Bcl-2, Bax, caspase-3, STAT3, NF-κB, p65, and Nrf2 protein. ^##p<0.01 and ^#p<0.05 compared with the control group; *p<0.05 compared with the testosterone group.