Therapeutic mechanisms of granulocyte-colony stimulating factor in methotrexate-induced parotid lesion in adult rats and possible role of telocytes: A histological study

Abstract

Background: Worldwide, Methotrexate (MTX) is used to treat neoplastic and non-neoplastic diseases despite its severe side-effects. One of these adverse effects is salivary dysfunction that can aggravate MTX mucotoxic effects. Such effects interfere with the patients' quality of life and increase morbidities and mortalities. Available treatments for salivary dysfunction have many drawbacks. Mobilization of bone marrow haematopoietic stem cells (BMHSCs) by human Granulocyte-Colony Stimulating Factor (G-CSF) used in many diseases showed promising results. Aim of the work: To detect the therapeutic effect of G-CSF on MTX-induced parotid lesion highlighting its possible mechanisms and the role of telocytes. Materials and Methods: Forty-one albino rats were divided into 3 groups; control, MTX and Neupogen-treated groups. All animals were weighed and sacrificed after 6 days. Parotid homogenates of 6 rats from each group were used to measure total protein concentration, amylase activity and malondialdehyde (MDA) value. The right parotids of the remaining animals of each group were processed to Paraffin blocks while, the left ones were processed to resin blocks. Paraffin sections stained with Hematoxylin and Eosin and immunohistochemical stains for CD34 and platelet-derived growth factor receptor-alpha (PDGFR-α) as well as resin semithin and ultrathin sections were examined. Body weight, biochemical results, number of immune-positive cells, difference between numbers of CD34+ and PDGFR-α+ cells (stem cells number), acini and ducts numbers and diameters were statistically analysed. Results: MTX group revealed diarrhoea, decreased body weight in addition to, degenerated acinar and ductal cells, and telocytes. However, Neupogen-treated group demonstrated almost normal histological features. Immunohistochemically, the treated group showed significant increase in CD34+ cells, PDGFR-α + cells and stem cells number versus MTX group. Conclusions: G-CSF had a therapeutic effect on MTX-induced parotid degeneration through its direct effects, BMHSCs mobilization and telocytes preservation.