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

Abstract

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.

Atrophy and Inflammatory Changes in Salivary Glands Induced by Oxidative Stress after Exposure to Drugs and Other Chemical Substances: A Systematic Review

“…A summary of their effects on histological or oxidative biomarkers on salivary glands is shown in Table 6. Hesperidin (HSP), a natural product with an antioxidative role successfully used as a treatment against chemotherapy toxicity, restored the biochemical markers modified by cyclophosphamide (CP) administration on male albino rats' salivary glands [15], while selenium (Se) reduced the damage induced by chemotherapy, as was shown by histology exam results, showing just minimal morphological alterations represented by mild degeneration of epithelial cells and vascular congestion, in male adult albino rats [12]. Hesperidin also has an anti-inflammatory effect, by reducing TNF-α and IL-1β [15].…”

“…In the PG, there was acinar distortion, periductal inflammation, confirmed also by an increase in inflammatory markers, such as TNF-α and IL-1β, and a reduced Ki67 immunopositivity in acinar cells [15]. In the SMG gland, there was parenchymal atrophy, necrosis, and apoptosis, the latter being indicated by BCL-2 (B cell lymphoma 2) negativity, along with periductal edema and fibrosis [12].…”

“…The second study has not analyzed the biochemical markers [12]. Morphological analysis has shown vacuolar degeneration in both the PGs and SMGs [12,15], parenchymal atrophy, acinar apoptosis or necrosis, periductal edema, and fibrosis at the level of the SMG [12].…”

“…6 articles on the effect of chemotherapy drugs on salivary glands [5,12,15,16,18,19]; • 4 articles on the effect of ethanol on salivary glands [6,7,9,20]; • 9 articles on the effects of heavy metals on salivary glands [2,11,[21][22][23][24][25][26][27]; • 3 articles on the effect of fluoride on salivary gland [4,10,28]; • 4 articles on the effect of other substances, such as atrazine [29], high protein diet [8], hyperoxia [30], and sodium nitrite [31];…”

“…In the SMG gland, there was parenchymal atrophy, necrosis, and apoptosis, the latter being indicated by BCL-2 (B cell lymphoma 2) negativity, along with periductal edema and fibrosis [12]. Co-administration of hesperidine in the case of the PG gland [15] and selenium in the case of the SMG has diminished the alterations [12]; • 5-Fluorouracil (5-FU), a pyrimidine analog with cytostatic activity, used for the treatment of different solid tumors, especially from the genital tract, could induce salivary gland atrophy and xerostomia. Studies from the literature have shown that 5-FU can provoke oxidative stress by inhibiting the antioxidative system and by increasing the activity of the oxidative system.…”