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. 2022 Jun 6;18(1):16.
doi: 10.1186/s13005-022-00320-7.

Effects of 4-hexylresorcinol administration on the submandibular glands in a growing rat model

Joo-Hyung Yoon  1 , Dae-Won Kim  2 , Suk Keun Lee  3 , Seong-Gon Kim  4
Affiliations

Effects of 4-hexylresorcinol administration on the submandibular glands in a growing rat model

Joo-Hyung Yoon et al. Head Face Med. .

Abstract

Background: 4-Hexylresorcinol (4HR) is a food additive and class I histone deacetylase inhibitor. In this study, we examined the effects of 4HR administration on the submandibular gland in a growing rat model.

Methods: Four-week-old rats were used in this study. The experimental group (nine males and eight females) received 12.8 mg/kg of 4HR weekly for 12 weeks. Ten rats (five males and five females) were used as controls. The submandibular glands of rats were collected 12 weeks after the first administration of 4HR. The weight of the glands was measured. Histological analysis, immunoprecipitation-high-performance liquid chromatography (IP-HPLC), and western blotting were performed.

Results: The weights of the rat submandibular glands were higher in the experimental groups than in the control group, especially in male rats (P < 0.05). The vascular endothelial growth factor (VEGF) and testosterone in the submandibular glands were more highly expressed in 4HR-treated male rats than in untreated rats, as detected by both western blotting and immunohistochemistry. The IP-HPLC results demonstrated that the expression levels of Ki67, epidermal growth factor, and testosterone in the submandibular glands were higher in 4HR-treated male rats than in untreated rats.

Conclusions: This study demonstrated that the systemic administration of 4HR increased the weight of submandibular glands in male rats. In addition, the testosterone and VEGF expression levels in the submandibular glands increased owing to 4HR administration.

Keywords: 4-hexylresorcinol; Angiogenesis; Salivary gland; Testosterone.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
The weight of the submandibular glands and histological findings. The weight of the submandibular glands in the 4HR group was significantly higher than that of the untreated control in males (*P = 0.036)
Fig. 2
Fig. 2
Histological findings of submandibular glands. Hematoxylin and eosin (H&E) stain and periodic acid-Schiff (PAS) stain. The low magnification view shows the submandibular gland (SM), the sublingual gland (SL), and lymph node (LN). The convoluted ducts (*) were well developed in the gland. There was no significant difference in the structure and size of the cells or the amount of fibrous tissue between the groups
Fig. 3
Fig. 3
Immunostaining for VEGF, testosterone, and Ki67. The staining intensity was higher in the 4HR group than in the untreated control group
Fig. 4
Fig. 4
Western blotting for VEGF and testosterone. The expression levels of both proteins were significantly higher in the 4HR group than in the untreated control
Fig. 5
Fig. 5
IP-HPLC results. 4HR-treated male rats showed increased expression levels of Ki-67, epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), transforming growth factor-β1 (TGF-β1), testosterone, and estrogen receptor-β (ERβ) compared to untreated male rats. 4HR-treated female rats showed decreased levels of growth hormone, Ki-67, and testosterone compared to untreated female rats
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