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

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.

4-Hexylresorcinol and Its Effects on Circumvallate Papillae Taste Buds in Diabetic and Healthy Rats: An Initial Investigation

“…In this regard, it is pertinent to address the decision to employ a single-dosage model. The chosen dosage of 4-HR for rat experiments was predicated on our previous research [25,26], and the selected dose aimed to elicit potential therapeutic effects without inducing significant morbidity or mortality. While this study serves as a preliminary investigation, it is acknowledged that employing a single-dosage model limits the understanding of the dose-response relationship and the potential efficacy of varied dosages of 4-HR.…”

“…The dosage determination considered safety data, including the LD50 for rats and the observed effects in cats. In addition, prior work demonstrated the efficacy of 4-HR at dosages close to the one chosen for this study, with notable effects such as decreased blood sugar levels [25,26]. For practicality in dosage calculations and to minimize potential errors, a dose of 10 mg/kg weekly was selected.…”

Role of Histone Deacetylases in the Pathogenesis of Salivary Gland Tumors and Therapeutic Targeting Options

“…Based on their structure, they are classified into small-chain fatty acids such as valproic acid (VPA) and butyrate acid, cyclic peptides/depsipeptide-FK228 (Romidepsin), hydroxamic acids (SAHA), LBH589 (Panobinostat), TSA (Trichostatin A), AR-42 (a hydroxamate-phenylbutyrate derivative), cyclic tetra-peptide (Trapoxin A) and benzamides (Entinostat/MS-275 and MGCD0103) [ 11 ]. Lately, the role of synthetic alkyl 4HR as a new HDACi has emerged [ 132 , 133 ]. Additionally, tumor angiogenesis is inhibited by a variety of actions that the hydroxamic derivative LBH589 has on endothelial cells [ 134 ].…”