The Effect of the Immunosuppressive Drug Sirolimus on structure of the Submandibular Salivary Glands of the Rat

Abstract

Background: Submandibular salivary glands are responsible for secretion of major amount of saliva which is important for normal oral environment of the oral cavity. Aim: to evaluate the effect of the Immunosuppressive drug Sirolimus on structure and immunohistochemistry of the submandibular salivary glands of the rats. Material and Methods Forty healthy adult male albino rats (body weight 150 -180 gram) were divided into two equal groups 20 animals each. Group 1 served as controls while group 2 were treated with the immunosuppressive drug sirolimus (rapamycin). Control group were subdivided into two subgroups subgroup 1.1: received ethanol and saline in comparable volume to group 2 and same route of administration while subgroup 1.2 were left untreated. After 3 months, rats were sacrificed and specimens of the right side of submandibular salivary glands were stained with H & E and Immunoperoxidase. While specimens of the left side were examined with transmission electron microscope. Results: Histologically, by H & E, both control subgroups showed normal structure of submandibular salivary gland. While, rats administrated sirolimus showed altered structure. Using TEM, the ultrastructural of submandibular salivary glands of both control subgroups showed normal architecture. While, sirolimus treatedgroup revealed degeneration in the glands acinar and ductal cells. Immunohistochemical findings showed normal staining reactivity of submandibular salivary gland of the control group while, sirolimus-treated group showed marked reduction in their staining reaction. Conclusion: Sirolimus administration cause structural and ultrastructural alterations in the parenchymal and stromal elements of the submandibular salivary gland that affect the salivary secretion and may lead to detrimental effect on oral health.

The long-term effects of multidrug immunosuppressive protocols based on calcineurin inhibitors and conversion to rapamycin on the morphology, apoptosis, and proliferation of rat salivary glands

“…Our results are in agreement with the findings of Soliman et al [ 18 ]. The authors revealed that the administration of rapamycin was associated with morphological changes in the rat submandibular salivary gland.…”

“…Other authors [ 16 , 18 ] have described more intense morphological changes in the salivary glands of animals after immunosuppressive treatment compared to our observations. These changes might result from the use of daily doses of immunosuppressive drugs that were higher than those applied in our experiment.…”

“…Dehpour et al [ 16 ] administered CsA at a dose of 25 mg/kg/day, while Spolidorio et al [ 17 ] administered 10 mg/kg/day. In turn, Soliman et al [ 18 ] used rapamycin at a dose of 10 mg/kg/day. It is worth highlighting that we applied doses of immunosuppressants that allowed us to obtain drug concentrations in the blood of the rats within the therapeutic range [ 19 ].…”

“…There are very few scientific reports on the effect of immunosuppressive drugs on the morphology of salivary glands [ 16 – 18 ]. Unfortunately, these reports show only the influence of single immunosuppressants on these glands.…”