The possible protective effect of Graviola extract on salivary gland against cytotoxicity during cisplatin treatment (Histological, Biochemical and Immuno-histochemical Study)

Abstract

• Objectives Chemotherapeutic agents affect both normal and cancer cells. Salivary glands are easily damaged. Protecting normal salivary tissues against the harmful side effects of cisplatin therapy is of great need. This study was designed to evaluate the cytoprotective effect of Graviola extract against cisplatin cytotoxicity on parotid and submandibular salivary glands.• Methods 30 adult male albino rats weighing 200-250 g were divided randomly into 3 equal groups: control group receiving only saline, cisplatin group receiving 6 mg/kg of cisplatin intraperitoneal and Graviola group receiving 6 mg/kg of cisplatin intraperitoneal followed by 100 mg/kg of Graviola extract daily orally for 14 days. At the end of the experiment parotid and submandibular glands were processed for H&E, VEGF and Ki-67 stains. Glutathione levels were detected from gland homogenates. • Results Histological evaluation of cisplatin group with H&E showed total loss of architecture and vacuolization in the parotid gland and serous part of the submandibular gland while the mucous part showed separation between the acinar cells and the intra-lobular ducts. With immunohistochemical stains, decreased number of proliferative cells was observed with Ki-67 stain and with VEGF stain the glandular cells showed the least levels of positive staining. Also, glutathione levels recorded the least values among the study groups. In the Graviola group, partial improvement of glandular architecture and decreased vacuolization in both glands, increased proliferative cells with Ki-67 and increase of VEGF expression and the highest value of glutathione levels were observed. • ConclusionGraviola extract partially ameliorates the cisplatin deleterious effect on the parotid and submandibular salivary glands at the histological and biochemical levels.