Long-term dexamethasone treatment alters the histomorphology of acinar cells in rat parotid and submandibular glands

Int J Exp Pathol. 2014 Oct;95(5):351-63. doi: 10.1111/iep.12092. Epub 2014 Sep 3.

Abstract

Glucocorticoids (GCs) induce insulin resistance (IR), a condition known to alter oral homeostasis. This study investigated the effects of long-term dexamethasone administration on morphofunctional aspects of salivary glands. Male Wistar rats received daily injections of dexamethasone [0.1 mg/kg body weight (b.w.), intraperitoneally] for 10 days (DEX), whereas control rats received saline. Subsequently, glycaemia, insulinaemia, insulin secretion and salivary flow were analysed. The parotid and submandibular glands were collected for histomorphometric evaluation and Western blot experiments. The DEX rats were found to be normoglycaemic, hyperinsulinaemic, insulin resistant and glucose intolerant (P < 0.05). DEX rat islets secreted more insulin in response to glucose (P < 0.05). DEX rats had significant reductions in the masses of the parotid (29%) and submandibular (16%) glands (P < 0.05) that was associated with reduced salivary flux rate. The hypotrophy in both glands observed in the DEX group was associated with marked reduction in the volume of the acinar cells in these glands of 50% and 26% respectively (P < 0.05). The total number of acinar cells was increased in the submandibular glands of the DEX rats (P < 0.05) but not in the parotid glands. The levels of proteins related to insulin and survival signalling in both glands did not differ between the groups. In conclusion, the long-term administration of dexamethasone caused IR, which was associated with significant reductions in both mass and flux rate of the salivary glands. The parotid and submandibular glands exhibited reduced acinar cell volume; however, the submandibular glands displayed acinar hyperplasia, indicating a gland-specific response to GCs. Our data emphasize that GC-based therapies and insulin-resistant states have a negative impact on salivary gland homeostasis.

Keywords: dexamethasone; glucocorticoids; glucose intolerance; insulin resistance; parotid gland; submandibular gland.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinar Cells / cytology*
  • Acinar Cells / drug effects
  • Animals
  • Blood Glucose / metabolism
  • Cell Shape
  • Dexamethasone / pharmacology*
  • Glucocorticoids / metabolism
  • Insulin / metabolism
  • Male
  • Parotid Gland / drug effects*
  • Parotid Gland / metabolism
  • Rats
  • Rats, Wistar
  • Salivary Glands / drug effects*
  • Salivary Glands / metabolism
  • Submandibular Gland / metabolism
  • Submandibular Gland / pathology*
  • Time

Substances

  • Blood Glucose
  • Glucocorticoids
  • Insulin
  • Dexamethasone