Impact of coadministration of apigenin and bone marrow stromal cells on damaged ovaries due to chemotherapy in rat: An experimental study

Abstract

Background: Apigenin is a plant-derived flavonoid with antioxidative and antiapoptotic effects. Bone marrow stromal cells (BMSCs) are a type of mesenchymal stem cells (MSCs) that may recover damaged ovaries. It seems that apigenin may promote the differentiation of MSCs.
 Objective: The aim of this study was to investigate the effect of coadministration of apigenin and BMSCs on the function, structure, and apoptosis of the damaged ovaries after creating a chemotherapy model with cyclophosphamide in rat.
 Materials and Methods: For chemotherapy induction and ovary destruction, cyclophosphamide was injected intraperitoneally to 40 female Wistar rats (weighing 180–200 gr, 10 wk old) for 14 days. Then, the rats were randomly divided into four groups (n = 10/each): control, apigenin, BMSCs and coadministration of apigenin and BMSCs. Injection of apigenin was performed intraperitoneally and BMSC transplantation was performed locally in the ovaries. The level of anti-mullerian hormone serum by ELISA kit, the number of oocytes by superovulation, the number of ovarian follicles in different stages by H&E staining, and the expression of ovarian Bcl-2 and Bax proteins by western blot were assessed after four wk.
 Results: The results of serum anti-mullerian hormone level, number of oocytes and follicles, and Bcl-2/Bax expression ratio showed that coadministration of apigenin and BMSCs significantly recovered the ovarian function, structure, and apoptosis compared to the control, BMSC, and apigenin groups (p < 0.001).
 Conclusion: The results suggest that the effect of coadministration of apigenin and BMSCs is maybe more effective than the effect of their administrations individually on the recovery of damaged ovaries following the chemotherapy with cyclophosphamide in rats.
 Key words: Apigenin, Bone marrow stromal cells, Chemotherapy, Ovary, Regeneration.

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Sesamol protects the function and structure of rat ovaries against side effects of cyclophosphamide by decreasing oxidative stress and apoptosis

“…Immunoreactive bands were demonstrated with a chemiluminescence detection kit (Amersham Biosciences) and quantified with Image J software. This protocol was performed three times on three ovaries in each group 6,10 …”

“…There are several methods for repairing damaged ovaries undergoing chemotherapy, but most are invasive, such as hormone therapy, stem cell transplantation, and ovarian tissue freezing 7–9 . One of the least dangerous ways to protect ovaries against chemotherapy is to use antioxidants 5,10 . Using an appropriate dose of antioxidants is noninvasive and can protect cells by reducing oxidative stress and scavenging reactive oxygen species (ROS) 11,12 .…”

“…Several studies have demonstrated that antioxidants can protect tissues against side effects of cyclophosphamide 15–17 . Moreover, some studies have shown that antioxidants such as l‐carnitine and apigenin can protect or improve damaged ovaries after chemotherapy with cyclophosphamide 5,10,18 . Therefore, it seems that other antioxidants may also protect the ovaries against the side effects of chemotherapy.…”

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