Protective effects of hesperidin in cyclophosphamide-induced parotid toxicity in rats

Cyclophosphamide (CYP) is an alkylating agent that is used on a wide range as a treatment of malignancies and autoimmune diseases. Previous studies have shown the promising role of hesperidin (HSP) as an antioxidant agent against various models of toxic agents. The protective effect of the HSP against CYP-induced parotid damage was evaluated in this study. Forty rats (180-200 g) were divided into four equal groups: Group I (received normal saline), Group II (HSP-treated at a dose of 100 mg/kg/day for 7 consecutive days), Group III (CYP-treated at a dose of 200 mg/kg single intraperitoneal injection on the 7th day of the experiment), Group IV (CYP + HSP); HSP-treated at a dose of 100 mg/kg/day for 7 consecutive days and CYP (200 mg/kg) single intraperitoneal injection on the 7th day of the experiment. Afterwards, the oxidative stress and inflammatory markers, the histopathological and immunohistochemical alterations of the parotid tissues in the studied groups were evaluated. CYP intoxication induced a significant parotid tissue injury represented by the elevation in the values of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and decrease in the catalase activity and glutathione peroxidase (GPx). Histologically, extensive histopathological alterations e.g., widely spaced serous acini with irregular shapes and congested blood vessels as well as downregulated ki-67 and alpha-smooth muscle actin (α-SMA) immunoexpression were induced by CYP. HSP administration markedly improved the biochemical and the histopathological studies. We can conclude that HSP elicited protective effects against the CYP-induced parotid toxicity.