Studies on the ameliorative potential of dietary supplemented different dose of selenium on doxorubicin-induced ovarian damage in rat.

Doxorubicin (Dox) may induce loss of follicles, resulting in the depletion of ovarian reserve and consequent premature ovarian failure. Selenium (Se) is an oligoelement with fundamental biological features and is among the most common chemical inhibitor compounds. The present study describes the curative effects of dietary supplementation with different Se doses on Dox-induced ovarian damage in rats. In this study, 64 adult female Wistar rats were randomly separated into eight groups: Control group, Dox group (5 mg/kg intraperitoneal [i.p.]), low-dose Se (0.5 mg/kg i.p.), middle dose Se (1 mg/kg i.p.), high dose (Se 2 mg/kg i.p.), Dox + low-dose Se group (0.5 mg/kg i.p.), Dox + middle dose Se (1 mg/kg i.p.), and Dox + high-dose Se group (2 mg/kg i.p.). After the experiment, ovarian follicles were counted, and Antimüllerian hormone, interleukin 1 beta, tumor necrosis factor alpha, and caspase-3 expression were determined. Levels of malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase were biochemically measured in ovarian tissue. Dox caused ovarian injury, as evidenced by significant changes in ovarian markers, histological abnormalities, and the debilitation of antioxidant defense mechanisms. Furthermore, Dox therapy significantly changed the expression of inflammatory and apoptotic markers. Dox + 1 mg Se with various saturations was studied, and this study demonstrated both histopathological and follicular reserve and more protective features. 1 mg Se pretreatment improved Dox-induced ovarian toxicity through alleviating the antioxidant mechanism, decreasing inflammation and apoptosis, and restoring ovarian architecture. As a result, our findings indicate that 1 mg Se is a promising therapeutic agent for the prevention of ovarian damage associated with Dox.

Protective effects of melatonin on female rat ovary treated with nonylphenol.

We investigated using histochemistry and immunohistochemistry ovarian damage caused by nonylphenol (NP) and the protective effect of melatonin treatment of NP induced ovarian damage. We used 21 female rats divided randomly into three groups: control, NP and melatonin + NP. Histopathological examination of the ovaries, and counting and classification of follicles were performed using Masson's trichrome staining. Expression of anti-Mullerian hormone (AMH), Bax, Bcl-2 and caspase-3 was detected in the ovaries using immunohistochemistry. Melatonin had an ameliorative effect on NP induced follicular atresia and absence of corpora lutea. More follicles were observed in the ovaries of animals treated with melatonin prior to treatment with NP. AMH immunoreactivity was significantly lower in the NP group than in the melatonin + NP group. NP increased immunostaining for Bax, Bcl-2 and caspase-3. Melatonin significantly reduced the increased expression of Bax, Bcl-2 and caspase-3 due to NP exposure. We found that pretreatment with melatonin is beneficial for protecting the ovaries from damage by NP.

The different doses of radiation therapy-induced damage to the ovarian environment in rats.

PURPOSE: The sequelae of premature loss of ovarian function can undoubtedly have undesirable effects for a woman although radiotherapy is one of the most relevant treatment modalities for various types of malignancies. The aim of this study was to determine the effect of different doses of radiation on ovarian folliculogenesis, inflammation, and apoptotic markers. MATERIALS AND METHODS: For this purpose, 40 healthy Wistar albino female rats divided into four groups: 1) Control group; 2) those that were exposed to total body 1 Gy of gamma rays; 3) those that were exposed to the total body 5 Gy of gamma rays, and 4) those that were exposed to total body 10 Gy of gamma rays. External irradiation to the total body was given with gamma irradiation delivered by the Co60 teletherapy machine. The day after radiation application the rats were sacrificed and the ovaries were removed in all groups. Histopathologic examination, follicle counting, and classification were performed in the ovarian tissues. The expression of AMH, TNF-α, IL1-ß, Bax, and Bcl-2 was detected. The stained sections were examined for caspase 3 positive apoptotic cell numbers. RESULTS: The recorded results revealed that increased radiation dose induced obvious ovarian injuries that were indicated by histopathological, and immunohistochemical alterations, including elevation of ovarian injury markers. A significantly lower number of total and primordial follicles was detected with increasing radiation dose compared with the control group. According to our immunohistochemical results, 10 Gy of gamma rays group had the lowest AMH expression levels, while had the highest TNF-α, IL1-ß expression level compared to the control group. When the groups were evaluated in terms of apoptosis, it was seen that the number of caspase 3 positive cells and Bax immunoreactivity intensity increased with radiation dose. In contrast, Bcl-2 immunoreactivity intensity decreased with increasing radiation dose compared with the control group. CONCLUSIONS: We demonstrate here that dose rate plays an important role when estimating the relation between exposure to an increased dose of ionizing radiation and the risk of ovarian disease. According to these results, certain factors have to be optimized before introducing them into clinics.

Raman spectroscopy: A novel experimental approach to evaluating cisplatin induced tissue damage.

The aim of this work is to clarify the effect of curcumin and beta-carotene on cisplatin-induced tissue damage and to demonstrate the potential of Raman spectroscopy to detect tissue changes consistent with liver and kidney histopathology as a potential diagnostic adjunct. In the study, 56 Wistar albino female rats were used and randomly divided into 7 groups (n:8). Sham group received only sesame oil; Cisplatin group, received a single dose injection of cisplatin; Beta-carotene group, treated with beta-carotene orally; Cisplatin + Beta-carotene group, pretreated with beta-carotene 30 min prior to the cisplatin injection, then received cisplatin; Curcumin group, orally treated with curcumin; Cisplatin + Curcumin group, pretreated with curcumin 30min prior to the cisplatin injection, then received cisplatin. The second application was performed 1 week after the first application. One of the liver and kidney tissues was taken to 10% form for histopathological examinations and the others were taken to -80 °C for raman spectroscopy. Received sections were hematoxylin-eosin stained. The avidin-biotin peroxidase method was used for to investigate anti-TNF-α and IL1-ß activities. TUNEL method was applied to determine apoptotic cells. According to our histopathological findings, beta-carotene and especially curcumin have been found to possess hepatorenal protective activities. These datas were supported by the microscopic damage scores. Although some of these findings were observed in both the cisplatin + curcumin and cisplatin + beta-carotene groups, the incidence and severity of histopathological lesions were less than the cisplatin group. Both immunohistochemical studies and Raman spectroscopy results consistent with histopathological examination of hematoxylen-eosin stained sections. Raman spectroscopy represents a suitable tool to provide insights into structural factors involved in the mechanisms underlying antitumor effects of platinum drug.

A new method for automatic counting of ovarian follicles on whole slide histological images based on convolutional neural network.

The ovary is a complex endocrine organ that shows significant structural and functional changes in the female reproductive system over recurrent cycles. There are different types of follicles in the ovarian tissue. The reproductive potential of each individual depends on the numbers of these follicles. However, genetic mutations, toxins, and some specific drugs have an effect on follicles. To determine these effects, it is of great importance to count the follicles. The number of follicles in the ovary is usually counted manually by experts, which is a tedious, time-consuming and intense process. In some cases, the experts count the follicles in a subjective way due to their knowledge. In this study, for the first time, a method has been proposed for automatically counting the follicles of ovarian tissue. Our method primarily involves filter-based segmentation applied to whole slide histological images, based on a convolutional neural network (CNN). A new method is also proposed to eliminate the noise that occurs after the segmentation process and to determine the boundaries of the follicles. Finally, the follicles whose boundaries are determined are classified. To evaluate its performance, the results of the proposed method were compared with those obtained by two different experts and the results of the Faster R-CNN model. The number of follicles obtained by the proposed method was very close to the number of follicles counted by the experts. It was also found that the proposed method was much more successful than the Faster R-CNN model.

Protective effects of curcumin and beta-carotene on cisplatin-induced cardiotoxicity: An experimental rat model.

OBJECTIVE: Cisplatin (CDDP) has been known to be an effective antineoplastic drug; however, it has a cardiotoxic effect. Curcumin (CMN) and beta-carotene (BC) have been suggested to protect biological systems against CDDP-induced damage. The current study was conducted to evaluate the possible protective roles of CMN and BC on CDDP-induced cardiotoxicity in rat cardiac tissues. METHODS: A total of 49 adult female Wistar albino rats were equally divided into seven groups as follows: control (no medication), sesame oil (1 mg/kg), CDDP (single dose injection two times as once a week, 5 mg/kg/week), BC (100 mg/kg), CDDP+BC (pretreated BC for 30 min before CDDP injection), CMN (200 mg/kg), and CDDP+CMN (pretreated CMN for 30 min before CDDP injection). These treatments were applied intraperitoneally for CDDP and with gavage for CMN and BC. The oxidative/antioxidant indicators, inflammatory cytokines, and histopathological alterations were examined. RESULTS: These alterations included a marked increase in malondialdehyde (MDA) level, significant decrease in catalase (CAT) and superoxide dismutase (SOD) activities, and significant elevation of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, interleukin (IL)-6 in the CDDP group compared with the other groups. Histopathologically, CDDP-induced severe myocardial degenerative changes were observed. However, the CDDP-induced disturbances in the above-mentioned parameters significantly improved by treatment with BC and particularly CMN. CONCLUSION: This study indicated that CDDP treatment markedly caused cardiotoxicity; however, treatment with CMN or BC ameliorated this cardiotoxicity in rats. Furthermore, these findings revealed that treatment with CMN has a higher cardioprotective effect than that with BC against CDDP-induced cardiotoxicity in rat cardiac tissues.