Common Salt Aggravated Pathophysiology of Testosterone-Induced Benign Prostatic Hyperplasia in Adult Male Wistar Rat

Abstract

Abstract Background Benign prostatic hyperplasia (BPH) is a major health concern in men associated with lower urinary tract symptoms and sexual dysfunction. Recurrent inflammation, decreased apoptotic rate and oxidative stress are some of the theories that explain the pathophysiology of BPH. Common salt, a food additive, is known to cause systemic inflammation and redox imbalance, and may serve as potential risk factors for BPH development or progression. This study examined the effect of common salt intake on the pathophysiology of testosterone-induced BPH. Methods Forty male Wistar rats were randomly divided into four groups (10 in each group): the control group and three salt diet groups-low salt diet (LSD), standard salt diet (SSD) and high salt diet (HSD). The rats were castrated, allowed to recuperate and placed on salt free diet (control), 0.25% salt diet (LSD), 0.5% salt diet (SSD) and 1.25% salt diet (HSD) for 60 days ad libitum. On day 33, BPH was induced in all the rats with daily injection of testosterone propionate (Testost®) for 28 days. The rats had overnight (12 hours) on day 60 and euthanized the following day in order to collect blood and prostate samples for biochemical, molecular and immunohistochemistry (IHC) analyses. Mean ± SD values were calculated and compared for significant difference with t-test (control and salt diet groups) and one-way ANOVA (in between salt diet groups) at p < 0.05. Results There was a significant rise in prostatic levels of IL-6, IL-8 and COX-2 in salt diet groups and moderate IHC staining of COX-2 in HSD group. The prostatic level of IL-17, IL-1β, PGE2, relative prostate weight and serum PSA levels were not statistically different. The concentrations of IGF-1, TGF-β were similar in all the groups but there was fold increase in Bcl-2 expression in salt diet groups-LSD (13.2), SSD (9.5) and HSD (7.9) and fold decrease in VEGF expression in LSD (-6.3), SSD (-5.1) and HSD (-14.1). Activity of SOD and concentration of nitric oxide increased in LSD and SSD groups, and SSD and HSD groups respectively. Activities of glutathione peroxidase and catalase, and concentration of NADPH and hydrogen peroxide were not significantly different. IHC result showed positive immunostaining for iNOS expression in all the groups whereas histopathology revealed moderate to severe prostate hyperplasia in salt diet groups. Conclusions There is a relationship between dietary salt intake and risk testosterone-induced BPH in Wistar rats, possibly, by promoting inflammation, oxidative stress, and suppressing apoptosis. These results reveal that intake of dietary salt at low, standard and high quantity aggravated the pathophysiology of testosterone-induced BPH in Wistar rats by promoting inflammation, oxidative stress, and suppressing apoptosis.