Ginger Ingredients Alleviate Diabetic Prostatic Complications: Effect on Oxidative Stress and Fibrosis

Abstract

Prostatic complications are common in patients with diabetes. This study investigated the effect of different ginger ingredients: zingerone, geraniol, and 6-gingerol on the prostate in diabetic rats. Diabetes was induced in Wistar rats by streptozotocin intraperitoneal injection (50 mg/kg), and the rats were left for 10 weeks to develop prostatic complications. In diabetic treated groups, rats received daily oral zingerone, geraniol, and 6-gingerol in doses of 20, 200, and 75 mg/kg, respectively, in the last 8 weeks. Treatment with the compounds caused changes in the ventral prostate of diabetic animals as indicated by the columnar ductal epithelium and dense secretions. There was an amelioration of oxidative stress as evidenced by the lowering of prostate malondialdehyde and elevating prostate oxidized to reduced glutathione (GSH/GSSG) ratios by geraniol and 6-gingerol. None of the three ginger ingredients affected the hyperglycemia, reduction in body weight gain, and testosterone deficiency seen in diabetic animals. Interleukin-1β and interleukin-6 levels remained unchanged. However, zingerone and geraniol ameliorated the fibrosis in diabetic prostate through suppressing the elevated prostate transforming growth factor beta 1 (TGFβ1) and collagen IV. Therefore, ginger ingredients could be beneficial in alleviating diabetic prostatic complications through suppressing oxidative stress and tissue fibrosis.

Figure 1

Photomicrographs show comparison between ventral prostate of control (a, c, e) and diabetic rats (b, d, f). Prostatic ductules (Pd) in control rats (a) were adhered together with minimal interductal spaces (IS) and had thick walls but in diabetic rats (b) their walls were relatively thin with marked irregular outlines (H&E ×40). Interductal spaces (IS) were wider in diabetic rats (d) and filled with connective tissue (CT) while, in control rats (c), connective tissue (CT) was a little amount between ductules (Masson's trichrome ×40). Most of epithelial cells in control rats (e) were columnar cells (arrows) while in diabetic rats (f) they were cuboidal (arrow) and even flat cells (arrow head). Secretions (stars) were darkly stained in control rats (e) and lightly stained in diabetic rats (f) (H&E ×400).

Figure 2

Ventral prostate of diabetic rats (D) and zingerone treated (DZ), geraniol treated (DR), and 6-gingerol treated (DG) diabetic rats. Wide interductal spaces were prominent in diabetic rats (D) in comparison with the diabetic treated groups (DZ, DR, and DG). In diabetic rats, ductal walls (arrows) were thin and undulated, while, in treated groups, ductal walls were relatively thicker and more uniform. Epithelial folds were always present in the external glandular layer in diabetic treated groups (H&E ×40).

Figure 3

Higher magnification of the preceding photomicrograph, ventral prostate in different groups; diabetic rats (D) and diabetic treated rats (DZ; DR; DG). Prostatic secretions (S) were darkly stained in diabetic treated groups when compared with diabetic ones; ductal walls (arrows) were clearly thicker in treated groups while, in diabetic group, they were thin (H&E ×100).

Figure 4

Photomicrographs show changes in the ductal epithelium (arrows) of the rat ventral prostate; diabetic rats (D), zingerone treated rats (DZ), geraniol treated rats (DR), and 6-gingerol treated rats (DG). Epithelial height was markedly increased in diabetic treated rats ((DR) and (DG)) and reached its highest limits in DZ group (H&E ×400).

Figure 5

Photomicrographs of rat ventral prostate show the interductal spaces (IS) in different groups; diabetic rats (D) and diabetic treated rats ((DZ), (DR), and (DG)). Relatively wide interductal spaces were recorded in diabetic group (D) and it contained connective tissue (CT) elements (Masson's trichrome ×100).

Figure 6

Measurements of postprandial glucose levels (mg/dl) (a), body weight gain percent (BWG%) (b), and serum testosterone levels (ng/ml) (c) in control (C), diabetic rats (D), zingerone treated rats (DZ), geraniol treated rats (DR), and 6-gingerol treated rats (DG), respectively (data are expressed as mean ± SE of the mean; ^∗p < 0.05 in comparison to controls (C)).

Figure 7

Measurement of the prostate malondialdehyde (a) and prostate GSH/GSSG ratios (b) in homogenized prostate tissues in control (C), diabetic rats (D), zingerone treated rats (DZ), geraniol treated rats (DR), and 6-gingerol treated rats (DG), respectively (data are expressed as mean ± SE of the mean; ^∗p < 0.05 in comparison to controls (C); ^#p < 0.05 in comparison to diabetic rats (D)).

Figure 8

Measurements of the levels of IL-6 (a) and IL-1b (b) expression in the prostate in control (C), diabetic rats (D), zingerone treated rats (DZ), geraniol treated rats (DR), and 6-gingerol treated rats (DG), respectively (data are expressed as mean ± SE of the mean; ^∗p < 0.05 in comparison to controls (C)).

Figure 9

Prostate TGFβ1 immunofluorescence in streptozotocin-induced diabetic rats, control (C), diabetic rats (D), zingerone treated rats (DZ), geraniol treated rats (DR), and 6-gingerol treated rats (DG). The primary chicken polyclonal antitransforming growth factor beta 1 (TGFβ1) and the mouse monoclonal anti-collagen I antibody and the secondary Alexa Fluor (λex = 555 and λex = 488, resp.) conjugated goat anti-chicken and goat anti-mouse were used (data are expressed as mean ± SE of the mean; ^∗p < 0.05 in comparison to controls (C); ^#p < 0.05 in comparison to diabetic rats (D)).

Figure 10

Prostate collagen IV immunofluorescence in streptozotocin-induced diabetic rats, control (C), diabetic rats (D), zingerone treated rats (DZ), geraniol treated rats (DR), and 6-gingerol treated rats (DG). The primary chicken polyclonal antitransforming growth factor beta 1 (TGFβ1) and the mouse monoclonal anti-collagen I antibody and the secondary Alexa Fluor (λex = 555 and λex = 488, resp.) conjugated goat anti-chicken and goat anti-mouse were used (data are expressed as mean ± SE of the mean; ^∗p < 0.05 in comparison to controls (C); ^#p < 0.05 in comparison to diabetic rats (D)).