P–443 Effects of capsaicin pre-treatment on ovarian follicle pool, inflammatory and apoptotic pathways against radiation induced ovarian failure

Abstract Study question Is capsaicin effective in preventing radiation induced ovarian follicle loss and premature ovarian failure (POF) in rats? Summary answer Capsaicin pre-treatment before radiotherapy restores especially primordial follicle pool, inhibits atresia of ovarian follicles, may be an acceptable therapeutic modality to prevent radiation induced POF. What is known already Ionizing radiation exposure to pelvic area induces inflammation, oxidative stress, follicular atresia and apoptosis; leading to POF. Phytochemicals were used in animal studies to prevent radiotherapy induced POF because of their antioxidant and anti-inflammatory properties however their potential radio-protective effects in human ovarian follicles are not clear. Capsaicin is the active compound of hot peppers and has anti-inflammatory and antioxidant properties. It was found that low dose capsaicin stimulated ovarian follicular development and proliferation of granulosa cells, inhibited apoptosis of ovarian follicles in pre-pubertal rat ovaries. However, no data exists on radio-protective effects of capsaicin on ovarian follicles. Study design, size, duration Twenty-four young adult Wistar albino female rats were housed under standard conditions (20 ± 1 0C room temperature, 60 ± 10% humidity, and a 12/12-h light/dark cycle) in regular cages and allowed free access to food and water. After 10 days of subcutaneous capsaicin 0,5 mg/kg/day or placebo treatment, animals exposed to total body irradiation of 8.3 Gy using a linear accelerator. Treatment continued for 1 day after irradiation. Participants/materials, setting, methods Rats were randomly divided into four groups: (1) control: non-irradiated rats were injected placebo; (2) capsaicin: non-irradiated rats were injected capsaicin; (3) radiation only (IR): rats were injected placebo before exposure to a single dose of 8.3-Gy whole body radiation; (4) Radiation-capsaicin (IR+CAP): rats were injected capsaicin prior to whole body irradiation and continued for 1 day after irradiation. Rats were sacrificed, blood samples were obtained for biochemical investigations. Ovaries were dissected for histopathological evaluation. Main results and the role of chance Radiation triggered oxidative stress, increased ovarian inflammation, increased follicular apoptosis and diminished ovarian follicle pool. Capsaicin was significantly ameliorated; oxidative stress by decreasing serum total oxidant status, oxidative stress index, disulfide, and malondialdehyde levels (p ≤ 0.001 both); ovarian inflammatory status by decreasing expressions of TNF-α, IL–1β, poly ADP-ribose polymerase–1 (PARP–1) (p = 0.002 both); apoptosis by decreasing expressions of active caspase–3 and p53 (p = 0.015 and p = 0.002 respectively); follicle counts by increasing primordial follicles and decreasing apoptotic follicles (p ≤ 0.001 both) in rats when administered before radiation exposure. Results of our study confirmed previously reported pro-proliferative and anti-apoptotic properties of capsaicin on ovarian follicles. These beneficial effects of capsaicin are demonstrated for the first time on ionizing radiation exposed rat ovaries. Limitations, reasons for caution Present study is a in-vivo rat study and other preclinical studies are needed to confirm our findings before moving forward to human trials. Radio-protective effects of capsaicin on rat ovarian follicles were demonstrated only in short term. Long term effects of capsaicin on folliculogenesis, fertilization and fecundity should be investigated. Wider implications of the findings: Preserving fertility is one of the main goals of successful radiotherapy in terms of quality of life for oncological or hematological diseases. Capsaicin treatment before radiotherapy may be an acceptable therapeutic modality to prevent radiation induced POF and has potential to utilize in clinical application in terms of fertility preservation. Trial registration number 218S876/2019