Moreover, our present results show that thymol has a superior ovarian reserve protection over the CAR effect. Natural flavonoids, Terpenoid and Thymoquinone are tested against different viral and host-cell protein targets. Lu Y, Wu C. Reduction of Salmonella enterica contamination on grape tomatoes by washing with thyme oil, thymol, and carvacrol as compared with chlorine treatment. [45] have documented the radioprotective effect of CAR against X-radiation in cultured human blood lymphocytes. +((!+[]+(!![])+!![]+!![]+!![]+!![]+!![]+!![]+[])+(!+[]+(!![])+!![]+!![]+!![])+(!+[]+(!![])+!![]+!![]+!![]+!![]+!![]+!![])+(!+[]+(!![])+!![]+!![]+!![])+(!+[]+(!![])+!![]+!![]+!![]+!![]+!![]+!![]+!![])+(!+[]+(!![])+!![]+!![]+!![]+!![]+!![]+!![]+!![])+(!+[]+(!![])+!![]+!![]+!![])+(!+[]-(!![]))+(!+[]+(!![])+!![]))/+((!+[]+(!![])+!![]+!![]+!![]+!![]+!![]+[])+(!+[]+(!![])+!![]+!![]+!![]+!![])+(!+[]-(!![]))+(+!![])+(!+[]+(!![])+!![])+(!+[]+(!![])+!![]+!![]+!![]+!![]+!![]+!![]+!![])+(!+[]-(!![]))+(+!![])+(!+[]+(!![])+!![]+!![]+!![]+!! Fan, Y. H. Li, G. J. Bagby, and C. H. Lang, “Modulation of inflammation-induced changes in insulin-like growth factor (IGF)-I and IGF binding protein-1 by anti-TNF antibody,”. (b) Expression of PCNA in the ovaries of rats subjected to, Carvacrol and Thymol Modulate the Cross-Talk between TNF-, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia, Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt, Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. However, PCNA immunoreactivity was present only in oocytes of primordial follicles with stain-free pregranulosa cells. Finally, peroxidase was detected with a working solution of diaminobenzidine (DAB) substrate (Novocastra), and sections were washed, counterstained with Mayer’s hematoxylin, and then mounted in DPX (dysterene, plasticizer, and xylene). Standard diet pellets contained not less than 20% protein, 5% fiber, 3.5% fat, 6.5% ash, and a vitamin mixture according to the standard guidelines. B. Thomson, F. Saran, and T. W. Kelsey, “Predicting age of ovarian failure after radiation to a field that includes the ovaries,”, K. Oktay, B. E. Harvey, A. H. Partridge et al., “Fertility preservation in patients with cancer: ASCO clinical practice guideline update,”, A. Imai, T. Furui, and A. Yamamoto, “Preservation of female fertility during cancer treatment,”, I. Adriaens, J. Smitz, and P. Jacquet, “The current knowledge on radiosensitivity of ovarian follicle development stages,”, D. Meirow, H. Biederman, R. A. Anderson, and W. H. B. Wallace, “Toxicity of chemotherapy and radiation on female reproduction,”, E. Buyuk, E. Nejat, and G. Neal-Perry, “Determinants of female reproductive senescence: differential roles for the ovary and the neuroendocrine axis,”, R. G. Gosden, J. C. Wade, H. M. Fraser, J. Sandow, and M. J. Faddy, “Impact of congenital or experimental hypogonadotrophism on the radiation sensitivity of the mouse ovary,”, W. H. B. Wallace, A. The results demonstrate the binding possibility of the natural compounds (Thymol, Carvacrol, Hesperidine, and Thymoquinone) to the viral main protease (Mpro). Carvacrol (CAR) and thymol are the major monoterpenic phenols, which occur in various essential oils among plant species such as Origanum, Thymus, and Corydothymus [22]. Rats were weighed daily until the day of sacrifice. Two days post irradiation, six rats in each group were utilized for biological assessment and three rats in each group were utilized for histopathology and immunohistochemistry studies. Therefore, the need for an effective radioprotective therapy is evident especially when none of the current clinically used modalities for radioprotection succeeds efficiently. Your browser will redirect to your requested content shortly. This cross-talk could control the inflammatory processes as well as the decision concerning apoptosis or cell survival [63]. In addition, Figure 2(c) shows a marked increase in serum FSH level (vs. in controls) two days post irradiation reaching 3.95-fold as compared to the control group. After fixation, specimens were dehydrated in an ascending series of alcohols, cleared in two changes of xylene and embedded in molten paraffin. In this study, gamma radiation induced a typical POF which was manifested in rats as low serum E2 and high FSH levels when compared with the control values; however, both CAR and thymol significantly improved the hormonal changes induced by irradiation. Eimeria spp. In the present study, concomitant treatment of irradiated rats with CAR or thymol has significantly inhibited TNF-α in the downstream signaling pathway of inflammation induced by irradiation. In contrast, CAR and thymol-irradiated rats showed a significant reduction in serum FSH levels as compared with the irradiated group; however, they are still higher than the control group as shown in Figure 2(c). Besides morphometric analysis, immunohistochemical detection of the proliferation marker, PCNA, proved that follicles belonging to the same follicular pool were at different states of maturation in control and irradiated ovaries as shown in Figure 3. NOTE: Your email address is requested solely to identify you as the sender of this article. These findings were in accordance with our previous study which suggested a role for this protein even in the earlier stages of folliculogenesis [53]. Recently, it was reported that the healthy antral follicular count (AFC) serves as a marker of ovarian reserve and correlates with serum AMH levels [39, 40]. Therefore, there is an urgent need to examine the ideal prevention strategies which function to protect the entire ovarian milieu from radiation damage [12]. The anatomy of misguided shielding of the ovaries,”, S. Irtan, D. Orbach, S. Helfre, and S. Sarnacki, “Ovarian transposition in prepubescent and adolescent girls with cancer,”, M. Hofer, Z. Hoferová, and M. Falk, “Pharmacological modulation of radiation damage. However, this rat model only offers information about the protection of carvacrol or thymol on the short-term negative impact of radiation, but investigations of longer-term effects on the primordial pool after irradiation is becoming necessary before advancing into human trials. Indeed, the IGF-1/IGF-1R axis acts as modulators of gonadotropins at the cellular level as well as stimulates granulosa cell proliferation and differentiation [18]. This could be explained as γ-irradiation induces apoptosis through a p21-mediated mechanism which directly inhibits PCNA in DNA replication [51]. We will be providing unlimited waivers of publication charges for accepted research articles as well as case reports and case series related to COVID-19. Carvacrol-induced [Ca2+]i rise and apoptosis in human glioblastoma cells. TAC was measured in ovarian homogenates according to the manufacturer’s instructions using a Randox assay kit (Randox Laboratories Ltd., Crumlin, UK). However, concurrent treatment with CAR and thymol significantly increased the healthy AFC to 4- and 5-fold of the irradiated group and reduced the atretic follicles to 0.42- and 0.58-fold of the irradiated group. Finally, this study is the first to explore the effect of CAR/thymol on the cross-talk between TNF-α and IGF-1 in radiotherapy-induced ovarian damage. Both essential oils restored the ovarian total antioxidant activity after a single dose of γ-irradiation. Our current study showed a correlated inverse relationship between TNF-α and IGF-1 in irradiated rats; this was in accordance with a previous study which found that Zymosan increased TNF-α, and this was associated with a 40% decrease in the IGF-I concentration in plasma, liver, heart, and brain [64]. Plant-derived chemopreventive agents exhibit limited side effects and less toxicity and at the same time protect the normal cells against radiation [21]. Due to its important role in follicular growth and in the ovulation process, serum IGF-1 was assessed using a commercially available kit, the Quantikine Rat/Mouse IGF-1 Immunoassay Kit (R&D Systems Inc.). After the primary antibodies were incubated and washed, slides were incubated with biotinylated anti-mouse IgG (Novocastra) for 30 min. Some pharmacological measures preserved the radiation-induced ovarian failure through their anti-inflammatory mechanisms such as zingerone [59], curcumin, and capsaicin [60].