Enhanced Kidney Damage Induced by Increasing Nonylphenol Doses: Impact on Autophagy-Related Proteins and Proinflammatory Cytokines in Rats.

Nonylphenol (NP) is an organic pollutant and endocrine disruptor chemical that has harmful effects on the environment and living organisms. This study looked at whether kidney tissues subjected to increasing doses of nonylphenol generated alterations in histopathologic, pro-inflammatory, and autophagic markers. Fifty rats were divided into five groups of ten each: group I: healthy group, II: control (corn oil), group III: 25 µl/kg NP, group IV: 50 µl/kg NP, group V: 75 µl/kg NP. The kidney tissue samples were obtained for histopathological, immunohistochemical, and biochemical analyses. The histological deteriorations observed in all NP groups included tubular epithelial cell degeneration, inflammation areas, and hemorrhage. The immunohistochemical investigations showed that NP significantly elevated the autophagy markers (Beclin-1, LC3/2, p62), pro-inflammatory cytokines (TNF-α, IL-6), HIF-1α, and eNOS in group III, IV and V compared with group I and II. The biochemical analysis also revealed that pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) increased in correlation with the NP doses, but only IL-1ß reached statistical significance in NP treated rats kidney tissue. The biochemical findings have been confirmed by the histological studies. The damage to renal tissue caused by NP exposure may worsen it by increasing inflammatory and autophagic markers.

Role of apoptosis and autophagy in folic acid-induced cytotoxicity of human breast cancer cells in vitro.

Obstacles to the successful treatment of breast cancer patients with chemotherapeutic agents can be overcome with effective new strategies. It is still unclear how folic acid affects the onset and spread of breast cancer. The purpose of this study was to determine how folic acid affected the apoptotic and autophagic pathways of the breast cancer cell lines MCF-7 and MDA-MB-231. In the present study, folic acid was applied to MCF-7 and MDA-MB-231 breast cancer cell lines at different concentrations and for different durations. MTT analysis was used to investigate cytotoxic activity. All groups underwent the Tunel staining procedure to identify apoptosis and the immunofluorescence staining approach to identify the autophagic pathway. 24-hour folic acid values were accepted as the most appropriate cytotoxic dose. In MCF-7, cell cycle arrest was observed in the S phase and MDA-MB-231 G1/G0 phases. When apoptotic TUNEL staining was evaluated in both cell lines, folic acid significantly increased apoptosis. While a significant difference was observed between the groups in terms of Beclin 1 immunoreactivity in the MDA-MB-231 cell line, there was no significant difference in the MCF-7 cell line. In addition, statistical significance was not observed LC3 immunoreactivity in both cell lines. In the study, it was observed that folic acid induced autophagy at the initial stage in the MDA-MB-231 cell line but had no inductive effect in the MCF-7 cell line. In conclusion, our findings showed that folic acid has a potential cytotoxic and therapeutic effect on MCF-7 and MDA-MB-231 breast cancer cell lines.

Effects of pseudoephedrine on rat fetal bone development: evaluation by three different methods.

Pseudoephedrine (PSE) is an agent that is contained in common cold medications. The agent, which is used to treat cold and cough, is the fourth most prescribed drug group in some countries. During pregnancy, expectant mothers use PSE for colds and other reasons. One out of every four expectant mothers use PSE alone or in combination with other medicines for various reasons. This study was aimed to investigate effects of PSE on long bones development in rat during fetal growth. Pregnant rats were divided into five groups: control and four experimental groups (25 mg/kg, 50 mg/kg, 100 mg/kg, 200 mg/kg PSE). Between 1 and 20 days of pregnancy, PSE was given to them by gavage. Weights and heights of fetuses isolated by cesarean on the 21st day were measured. Ossification of femur and humerus was examined by three different methods mentioned earlier. Depending on the dose increase, all morphometric data, ossification rate and bone length of the fetuses were decreased. Besides, it was determined that the amount of Calcium in the bone tissue decreased in the analyzes made with SEM-EDX Analysis. The data obtained from this study reveal that the use of PSE during pregnancy disrupts the existing balance in the bone and negatively affects ossification due to the dose increase. In conclusion, we present descriptive and novel data on the effects of PSE use during pregnancy on the bone development of rat fetal long bones.

Effect of systemic atorvastatin on bone regeneration in critical-sized defects in hyperlipidemia: an experimental study.

PURPOSE: Hypocholesterolemic medications similar to atorvastatin are efficient in lowering blood lipid levels; however, compared to other medications in the statin family, their impact on bone metabolism is claimed to be insufficient. The impact of atorvastatin on bone regeneration in dental implantology in individuals with hyperlipidemia who received atorvastatin in the clinic is doubtful. METHODS: In the study, 16 male New Zealand rabbits of 6 months were used. All rabbits were fed a high-cholesterol diet for 8 weeks, and hyperlipidemia was created. It was confirmed that the total cholesterol level in rabbits was above 105 mg/dl. A critical-sized defect was created in the mandible. The defect was closed with xenograft and membrane. Oral 10 mg/kg atorvastatin was started in the experimental group, and no drug was administered in the control group. At 16th week, animals were sacrificed. For histomorphological examination, the new bone area, osteoclast, and osteoblast activities were evaluated. RESULTS: While new bone area (45,924 µm2, p < 0.001) and AP intensities (105.645 ± 16.727, p = 0.006) were higher in the atorvastatin group than in the control group, TRAP intensities in the control group (82.192 ± 5.346, p = 0.021) were higher than that in the atorvastatin group. CONCLUSIONS: It has been found that high blood lipid levels will adversely affect bone graft healing and the use of systemic atorvastatin contributes to bone healing. Clinicians should pay attention to the selection of surgical materials, considering the importance of questioning drug use in their patients and the risks in cases of non-use.

Cytotoxicity screening of Thymus vulgaris L. in breast cancer: in vitro study.

Breast cancer is one of the leading causes of cancer-related deaths due to its aggressive course. There is an increasing need for alternative therapy strategies, including herbal medications, to treat the disease because of its high incidence. Medicinal plants, such as Thymus vulgaris L. (T. vulgaris), have recently attracted great interest due to the antitumor properties of their extracts. The purpose of this investigation was to ascertain whether T. vulgaris had any cytotoxic effects on two different breast cancer cell lines. MTT test was applied to evaluate the effect of T. vulgaris on cell viability. TUNEL method was used to determine its apoptotic effect. LC3 and Beclin-1 expression levels were determined by immunofluorescence staining method and its autophagic effect was evaluated. Our findings demonstrate that T. vulgaris greately lowers proliferation, both in terms of concentration and duration. Consistent with decreased proliferation, an increase in apoptotic and autophagic cell death were also observed. The migration capacity of MCF-7 and MDA-MB-231 breast cancer cells was greatly suppressed by T. vulgaris, while significantly reducing colony formation. This study is the first to look into how T. vulgaris methanol extract affects breast cancer cells. All of these findings demonstrate that T. vulgaris prevents breast cancer cells from developing a malignant phenotype. It is possible to say that the methanol extract of T. vulgaris is suitable for the treatment of breast cancer, including aggressive types. However, in vivo research should support these results.

Protective Effects of Boric Acid Taken in Different Ways on Experimental Ovarian Ischemia and Reperfusion.

Ovarian ischemia is a gynecological emergency that occurs as a result of ovarian torsion, affects women of reproductive age, and reduces ovarian reserve. The current study was designed to investigate the effect of boric acid taken in different ways on histopathological changes, autophagy, oxidative stress, and DNA damage caused by ischemia and reperfusion in the ovary of adult female rats. We established seven groups of 70 adult female rats: untreated control, intraperitoneal boric acid group (IpBA), oral boric acid group (OBA), ischemia/reperfusion group (ischemia/2 h reperfusion; OIR), ischemia/reperfusion and local boric acid group (OIR + LBA), ischemia/reperfusion and intraperitoneal boric acid group (OIR + IpBA), and ischemia/reperfusion and oral boric acid group (OIR + OBA). On the 31st day of the experimental procedure, both ovaries were harvested for histologic (hematoxylen and eosin and Masson trichrom), biochemical (ELISA and AMH, MDA, SOD, and CAT analyses), and comet evaluation. In the OIR group, hemorrhage, edema, inflammation, and diminished follicle reserve were seen in the ovary. Boric acid treatment reduced the ovarian ischemia/reperfusion damage, and the follicles exhibited similar morphological features to the control group. Moreover, boric acid treatment decreased the levels of Hsp70, NF-KB, COX-2, and CD31, which increased as a result of OIR. On the other hand, SCF and AMH levels, which decreased as a result of OIR, increased with boric acid treatment. The levels of autophagy markers (Beclin-1, LC3, and p62) reached values close to those of the control group. According to the biochemical findings, it was concluded that boric acid is also effective on oxidative stress, and the AMH level was particularly high in the OIR + OBA group, consistent with the immunohistochemical staining result. In addition, it was observed that the DNA damage caused by OIR reached values close to those of the control group, especially in the OBA after OIR. This study showed the therapeutic effects of boric acid on OIR injuries; thus, boric acid may be a potential therapeutic agent for ovarian protection and fertility preservation in cases that may cause ovarian torsion.

The effect of different treatment protocols with diode laser on regeneration in axonetmesis injuries of the inferior alveolar nerve: an animal study.

The inferior alveolar nerve can be damaged during dental procedures, leading to symptoms, such as tingling, numbness, and reduced quality of life. Recovery depends on factors such as medications, surgery, and photobiomodulation therapy. Photobiomodulation therapy has shown the potential to improve nerve function and reduce regeneration time; however, there is no standard treatment protocol yet. This study aimed to examine the effect of diode lasers on nerve regeneration in patients with axonetmesis injuries. In this experiment on animals, Wistar rats' damaged sensory systems were treated with lasers to restore them. Animals were randomly divided into six groups: a sham group, a control group, and four laser treatment groups(1st group: performed every day, 10 sessions; 2nd group: performed every 2 days, 10 sessions; 3rd group: performed every day, 20 sessions; and 4th group: performed every 2 days, 20 sessions). Sensory function was determined using the Semmes-Weinstein monofilament test, which was repeated after the surgical procedure. The results showed that the 20-session group had the best improvement, most closely resembling the group without sensory test damage. The histomorphometric results showed that the number of axons was significantly lower in the group that received 10 daily sessions and in the control group than in the undamaged nerve. Axon diameter was lower in all groups than in the sham group. In conclusion, the remarkable aspect of this study is that consecutive-day 20-session laser treatment showed better improvement than the over-the-day 20-session treatment protocol.

Semicarbazides Carrying Indole Core: Synthesis, Cytotoxicity Evaluation against Human Breast Cancer Cell Lines, and Molecular Modeling Studies.

In this article, we report the synthesis and cytotoxicity evaluation of novel indole-carrying semicarbazide derivatives (IS1-IS15). The target molecules were obtained by the reaction of aryl/alkyl isocyanates with 1H-indole-2-carbohydrazide that was in-house synthesized from 1H-indole-2-carboxylic acid. Following structural characterization by 1 H-NMR, 13 C-NMR, and HR-MS, IS1-IS15 were investigated for their cytotoxic activity against human breast cancer cell lines, MCF-7 and MDA-MB-231. According to the data obtained from the MTT assay, phenyl ring with a lipophilic group at its para-position and alkyl moiety were preferential substituents on the indole-semicarbazide scaffold for antiproliferative activity. The effect of IS12 (N-(4-chloro-3-(trifluoromethyl)phenyl)-2-(1H-indole-2-carbonyl)hydrazine-1-carboxamide), the compound that demonstrated remarkable antiproliferative activity on both cell lines, was also evaluated on the apoptotic pathway. Moreover, the calculation of critical descriptors constituting drug-likeness confirmed the position of the selected compounds in the anticancer drug development process. Finally, molecular docking studies suggested the inhibition of tubulin polymerization as the potential activity mechanism of this class of molecules.

The effect of different doses of nonylphenol on the blood-testicular barrier integrity, hormone level, and DNA damage in the testes of rats.

Determining the molecular characteristics of the damage caused by NP exposure in the testis is very important for understanding the source of the damage and developing treatment methods accordingly. Therefore, in this study, it is aimed to evaluate the toxic effects that different doses of NP may cause in the testis, including blood-testicular barrier integrity and sperm DNA damage. For this purpose, 50 adult male Wistar albino rats were used in the study. Low, medium, and high-dose NP groups and the corn oil group were formed. After NP administration at determined doses for 15 days, the testis tissue taken under anesthesia was fixed in formaldehyde. Paraffin blocks were embedded using the routine histological tissue follow-up method. Histopathological and immunohistochemical analyses were performed by taking 5 µm thick sections from paraffin blocks. The other testicular tissue was taken for the Western blot, Elisa, and comet methods, and the findings of sperm DNA analysis and the blood-testicular barrier were examined. NP caused the seminiferous epithelium to be disorganized and have significantly fewer cells in the testes of rats in different dose NP-induced groups. Compared with the control group, mTOR, Cx43, SCF, and HSP70 protein levels were decreased, while the expression of MMP-9 levels was increased in the different NP dose groups. Furthermore, tissue testosterone and inhibin B levels and SF-1 immunoreactivity intensity gradually decreased depending on the dose increase of NP. DNA damage of testicular tissues were increased in NP groups depending on NP dose. These results suggest that it is evident that NP, a commonly used industrial chemical, is an endocrine disrupting chemical (EDC) with estrogenic activity exerting adverse effects on health and that urgent measures are needed regarding the use.

Therapeutic potential of hesperidin: Apoptosis induction in breast cancer cell lines.

Hesperidin is a flavonoid commonly found in citrus fruits. Studies have shown that hesperidin has anti-inflammatory, analgesic, and antimicrobial properties, as well as its effectiveness in carcinogenesis. In this paper, we aim to investigate the molecular mechanisms of hesperidin-induced apoptosis in MCF-7 and MDA-MB-231 cancer cells. The inhibitory effect of hesperidin on cellular proliferation was evaluated with the MTT assay. Cell cycle analysis of hesperidin-treated cells was then performed, as well as immunocytochemical analysis of the effect on the apoptosis pathway (TUNEL, Bax, and Bcl-2 expression). Moreover, hesperidin induced cellular apoptosis in MCF-7 breast cancer cells by inhibiting Bcl-2 and enhancing Bax expression at protein levels. On the other hand, hesperidin caused apoptosis in the MDA-MB-231 breast cancer cell line, but it did not activate the Bax/Bcl-2 pathway. Hesperidin also induced cell cycle arrest at the S phase in the MCF-7 and MDA-MB-231 cell lines. These findings showed that hesperidin is a potential therapeutic candidate for preventing the progression of breast cancer. In addition, hesperidin could significantly stimulate the death mechanisms in ER/PR (+) MCF-7 cells by changing the expression balance of Bax and Bcl-2 proteins, but lead ER/PR (-) MDA-MB-231 breast cancer cells to apoptosis in a different way.

Nonylphenol Exposure-Induced Oocyte Quality Deterioration Could be Reversed by Boric Acid Supplementation in Rats.

In this study, we reported boric acid's protective effects on the quality of nonylphenol (NP)-exposed oocytes. Female rats were classified into 4 groups: control, boric acid, NP, and NP+boric acid. Histopathological studies and immunohistochemical analysis of anti-müllerian hormone (AMH), mechanistic target of rapamycin (mTOR), Sirtuin1 (SIRT1), stem cell factor (SCF) studies were done. The comet assay technique was utilized for DNA damage. The ELISA method was used to determine the concentrations of oxidative stress indicators (SOD, CAT, and MDA), ovarian hormone (INH-B), and inflammation indicators (IL-6 and TNF-α). Boric acid significantly reduced the histopathological alterations and nearly preserved the ovarian reserve. With the restoration of AMH and SCF, boric acid significantly improved the ovarian injury. It downregulated SIRT1 and upregulated the mTOR signaling pathway. It provided DNA damage protection. Ovarian SOD, CAT levels were decreased by boric acid. Boric acid co-administration significantly reduced NP's MDA, IL-6, and TNF-activities. This results imply that boric acid has a protective role in ovarian tissue against NP-mediated infertility.

Melatonin has an inhibitory effect on MCF-7 and MDA-MB-231 human breast cancer cell lines by inducing autophagy and apoptosis.

The goal of this work was to see how melatonin affected Bax and Bcl-2 expression, as well as apoptosis and autophagy, in MCF-7 and MDA-MB-231 breast cancer cell lines, which have distinct hormonal sensitivities. In this study, to investigate the IC50 value of melatonin, varied melatonin concentrations were administered to MCF-7 and MDA-MB-231 breast cancer cell lines. Moreover, cytotoxic activities were analyzed through MTT analysis. Five subgroups were created for both cell lines: control, IC50-MeL, hIC50-MeL, DMSO1, and DMSO2. To evaluate the apoptotic effect of melatonin, immunofluorescence staining methods of TUNEL, Bax, and Bcl-2 were used, and to examine the effects of autophagy, immunofluorescence staining methods of Beclin-1, LC3, and p62 were used. In vitro results revealed upregulation of the expression of TUNEL and Bax in both MCF-7 and MDA-MB-231 cell lines regarding dose and time, but downregulation of Bcl-2 expression. Moreover, autophagy results were consistent with in vitro apoptosis results in both MCF-7 and MDA-MB-231 cell lines. We determined that the expressions of the autophagy markers Beclin-1, LC3, and p62 were increased. Our findings indicate that treatment of breast cancer cells with melatonin increased the inhibitory effect of melatonin on cell growth through both apoptosis and autophagy in vitro. Consequently, it was concluded that melatonin might adjust the expression balance of markers that have a role in cell death mechanisms and significantly promote these mechanisms. Therefore, melatonin can inhibit the growth of breast cancer cells by inducing cell death.

The effect of pulsed radiofrequency application on nerve healing after sciatic nerve anastomosis in rats.

The Effect of Pulsed Radiofrequency Application on Nerve Healing After Sciatic Nerve Anastomosis in Rats. In this study, we aimed to evaluate the histomorphological and functional effect of Pulsed Radiofrequency (PRF) application on regeneration after experimental nerve damage in rats. Forty Sprague-Dawley male rats were used in the study. Sciatic nerve incision was applied to all rats and then anastomosis was performed. Twenty rats were separated as the control group, and the remaining 20 rats underwent PRF every day at 42oC, for 120 seconds. The groups were divided into two further subgroups to be sacrificed on the 15th and 30th days. Tissue samples were obtained from all groups at 24 hours and 72 hours after the injury. Sections of sciatic nerve samples were stained with hematoxylin-eosin for light microscopic investigation and prepared for evaluation of ultrastructural changes with transmission electron microscopy. In the evaluation of axon numbers and diameters were seen that the 30th-day RF group had an increase compared to the control group. In the electron microscopic examination, it was observed that myelinated and unmyelinated nerve fiber sheaths had borders that are more regular in the RF group, the nucleus structures of schwann cells were better preserved, mitochondrial damage was less, and the extensions of fibroblast and collagen fibers were smoother than the control group. The findings suggested that PRF application has a positive contribution histologically on nerve healing in the early period after full-layer incision nerve injury anastomosis surgery.

Hepatotoxicity and renal toxicity induced by radiation and the protective effect of quercetin in male albino rats.

PURPOSE: Although radiation is one of the basic methods commonly used in cancer treatment, it inevitably enters the field of treatment in healthy tissues and is adversely affected by the acute and chronic side effects of radiation. This study evaluated the possible protective effects of quercetin, an antioxidant agent, against liver and kidney damage in rats exposed to a whole-body single dose of radiation (10 Gy of gamma-ray). MATERIALS AND METHODS: The study groups were formed as control, sham, quercetin, radiation, quercetin + radiation and radiation + quercetin using 60 male Wistar albino (200-250 g, 3 months old) rats, including 10 rats in each group. The gamma-ray provided by the Co60 teletherapy machine was given to the whole body as external irradiation. According to the groups, quercetin was administered to rats at 50 mg/kg/day via oral gavage before or after radiation administration. The rats were sacrificed the day after irradiation and the extracted tissue samples from all groups were compared histologically and immunohistochemically. DNA damage was determined by the neutral comet assay technique. Also, malondialdehyde (MDA) and glutathione peroxidase (GSH) were evaluated in liver and kidney tissues by the ELISA method. RESULTS: Histopathological changes were observed altered morphology of liver and kidney tissues in the radiation groups. Sinusoidal dilatations, vacuolization, and hepatic parenchyma necrosis in the liver, while in kidneys, glomerular shrinkage, widened Bowman's space, tubular dilatation, and inflammation were evident. TNF-α, IL1-α, HIF1-α, and caspase 3 immunoreactivities in tissues were determined by immunohistochemistry. High caspase 3 positive cell number confirmed apoptosis, the comet parameters were decreased in the quercetin + radiation group. When compared to the control group, the exposure to radiation showed a marked elevation in MDA which was accompanied by high GSH. This damage was reduced in the quercetin + radiation group. CONCLUSIONS: With the results obtained from the study; Quercetin is thought to have a protective potential against radiation-induced liver and kidney damage due to its radioprotective effect.

Use of selenium to ameliorate doxorubicin induced hepatotoxicity by targeting pro-inflammatory cytokines.

Doxorubicin (DOX) is a widely used drug for the treatment of cancer,but its clinical use is limited by its liver toxicity. Administering DOX with an antioxidant has become a strategy for preventing the side effects of DOX. Although selenium (Se) is an important trace mineral, data concerning the effect of Se on DOX induced liver tissue are lacking. We investigated the mechanism of DOX hepatotoxicity and the protective effect of different doses of Se on Dox induced liver damage. Female Wistar albino rats were divided into eight equal groups. Se was injected intraperitoneally (i.p.) to rats at doses of 0.5, 1, and 2 mg 0.5 h after injection i.p. of 5 mg/kg DOX on days 1, 7, 14, 21 and 28. Liver histopathology was assessed to determine the dose at which Se may best inhibit Dox induced liver toxicity. Also, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) expression levels and proliferating cell nuclear antigen (PCNA) activity were determined using immunohistochemistry. We found that DOX caused liver damage and increased TNF-α, IL-1ß and PCNA levels. Se prevented structural damage to liver tissues. Our findings reinforce the protective effects of Se in rat liver.

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.

The effects of apoptosis and apelin on lymph node metastasis in invasive breast carcinomas.

This study aimed to evaluate the biological and clinical significance of apelin-36 in breast cancer and to compare apelin-36 expression and apoptotic index in both breast tissue and metastatic lymph nodes in patients with invasive breast carcinoma. In this study, both tumor tissue and metastatic lymph nodes of the same patient were collected from 60 cases of invasive breast carcinoma patients (IDC, ILC) and 20 cases of normal breast tissue with no tumor from mammoplasty were used as the control group. The expression of apelin was examined with immunohistochemically, and the apoptotic index was examined with TUNEL methods. According to Kruskal-Wallis analysis, there was a significant difference between IDC and the control group when the apelin expression was compared between the breast tissues (p = 0.001). There were significant differences between the three groups when comparing relationships with apoptotic index (p < 0.001). According to the Mann-Whitney U test, both tumor size and expression of apelin in lymph nodes in ILCs were significantly higher than IDCs. (p = 0.026, p = 0.024, respectively). According to correlation analysis, there was a good correlation between the expression of apelin in breast tissue and apelin expression in lymph nodes (p = 0.000). It is also found a similar relationship in terms of the apoptotic index (p = 0.000). In addition, the negative correlation was found between apelin expression and the apoptotic index in breast tissues (p = 0.003). Based on these results, apelin-36 can be used as a marker for determining the metastasis potential in invasive breast cancer.

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.

Progesterone decreases the extent of ovarian damage caused by cisplatin in an experimental rat model.

BACKGROUND: Apart from the role of progesterone in reproductive physiology, the protective role of exogenously administered progesterone was observed in various injuries, such as neurologic defects and acute kidney injury. OBJECTIVES: The aim of the present study was to investigate the effects of progesterone therapy on the immunoexpression of anti-Müllerian hormone (AMH) and the number of apoptotic cells in ovarian damage induced with cisplatin, a chemotherapeutic agent, in an experimental rat model. MATERIAL AND METHODS: Forty rats were randomly divided into 4 groups; the control group (the saline group), the cisplatin-treated group (rats were injected with 5 mg/kg/week cisplatin intraperitoneally (i.p.)), the cisplatin + progesterone-treated group (the rats were pretreated with 8 mg/kg progesterone intramuscularly (i.m.) (8 mg/kg) before they were injected with 5 mg/kg/week cisplatin i.p.), and the progesteronetreated group (the rats were treated with 8 mg/kg progesterone i.m.). The ovaries were removed from the rats in all groups 5 days after the final injection of cisplatin. RESULTS: Histopathologic examination and follicle counting were performed. The immunoreactivity intensity of AMH and apoptosis were compared. Histological analysis of the ovaries treated with cisplatin showed ovarian damage. Immunohistochemical analysis showed that the immunoreactivity intensity of AMH, a biomarker that discriminates the degree of ovarian damage, was lower in the cisplatin-treated groups than in other groups. Terminal deoxynucleotide transferase-mediated 20-deoxyuridine 50-triphosphate nick endlabeling (TUNEL) assays showed that the increase in the number of apoptotic cells was statistically significant in the cisplatin-treated group compared to the control group (p < 0.05). Progesterone administration with cisplatin resulted in decreases in TUNEL-positive cells. The decrease in the number of apoptotic cells was statistically significant in the cisplatin + progesterone-treated group compared to the control group (p < 0.001). CONCLUSIONS: Our results showed that using progesterone as an adjuvant agent against ovarian damage in patients undergoing cancer chemotherapy with cisplatin is beneficial.

A Humanized Anti-Interleukin 6 Receptor Monoclonal Antibody, Tocilizumab, for the Treatment of Endometriosis in a Rat Model.

OBJECTIVE: The aim of this study was to investigate the efficacy of anti-interleukin 6 (IL-6) therapy in the treatment of endometriosis in a rat model. STUDY DESIGN: After the peritoneal implantation of autologous endometrial tissue, 22 Wistar female rats were divided to create 2 intervention groups: the tocilizumab group (n = 13) and the control group (n = 9). After measuring implant volume, saline was administered to the rats in the control group and 8 mg/kg tocilizumab was administered intraperitoneally to the rats in the tocilizumab-treated group every 2 weeks. After a 4-week treatment period, the volumes and histopathological properties of the implants were evaluated. A scoring system was used to evaluate the preservation of epithelia. Fibrosis score was assessed between the groups. Ectopic and eutopic endometrium were evaluated immunohistochemically for IL-6 and vascular endothelial growth factor (VEGF). RESULTS: There was a significant difference between the volumes of implants before and after treatment in the tocilizumab group (P < .05). The posttreatment volumes of lesions were smaller in the tocilizumab group than in the control group. Histologic and fibrosis scores were lower in the tocilizumab group than in the control group. Immunoreactivity intensity for VEGF was significantly decreased in the tocilizumab group for ectopic and eutopic endometrium (P < .05). Interleukin 6 levels and endometrial thickness for ectopic and eutopic endometrium were similar between the groups. CONCLUSION: Tocilizumab treatment had a regressive effect on the endometriotic implants.