Chlorogenic acid attenuates cisplatin-induced ovarian injury in rats.

The aim of this study was to determine the possible therapeutic effect of chlorogenic acid (CGA) on cisplatin (CDDP)-induced ovarian damage in rats. Rats were first exposed to CDDP (5 mg/kg) and then treated CGA (1.5 and 3 mg/kg) for three days. Oxidative stress (OS), inflammation and apoptosis markers were determined using spectrophotometric methods. Ovarian tissues were also evaluated histologically. The levels of OS, inflammation and apoptosis biomarkers increased by CDDP administration (p < 0.05). Treatments with CGA significantly alleviated these markers dose-dependently (p < 0.05). These data reveal that CGA may exert an ovoprotective effect by reducing pro-inflammatory mediators and enhancing antioxidant status in ovarian tissue.

Ethyl pyruvate attenuates cisplatin-induced ovarian injury in rats via activating Nrf2 pathway.

Although cisplatin (CDDP) is an antineoplastic drug widely used for the treatment of various tumors, its toxicity on the reproductive system is a concern for patients. Ethyl pyruvate (EP) possesses potent antioxidant and anti-inflammatory activities. The objective of this study was to evaluate the therapeutic potential of EP on CDDP-mediated ovotoxicity for the first time. Rats were exposed to CDDP (5 mg/kg) and then treated with two doses of EP (20 and 40 mg/kg) for 3 days. Serum fertility hormone markers were evaluated using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers were also determined. In addition, how CDDP affects the nuclear factor erythroid 2-associated factor 2 (Nrf2) pathway and the effect of EP on this situation were also addressed. EP improved CDDP-induced histopathological findings and restored decreasing levels of fertility hormones. EP treatment also reduced the levels of CDDP-mediated OS, inflammation, ERS and apoptosis. In addition, EP attenuated CDDP-induced suppression in the levels of Nrf2 and its target genes, including heme oxygenase-1, NAD(P)H quinone dehydrogenase-1, superoxide dismutase and glutathione peroxidase. Histological and biochemical results showed that EP can have therapeutic effects against CDDP-induced ovotoxicity with antioxidant, anti-inflammatory and Nrf2 activator activities.

The ameliorative effect of Primula vulgaris on cisplatin-induced nephrotoxicity in rats and quantification of its phenolic components using LC-ESI-MS/MS.

Cisplatin (CDDP) is an important chemotherapeutic agent, accumulation of which in kidney tissue causes nephrotoxicity and renal failure. The aim of this study was to evaluate, for the first time in the literature, the protective effect of dimethyl sulfoxide (DMSO) extract of Primula vulgaris leaf (PVE) against CDDP-induced nephrotoxicity in rats. The PVE content was characterized using liquid chromatography-mass spectrometry. Nephrotoxicity was induced with a single dose of CDDP (7.5 mg/kg). Thirty female Wistar-Albino rats were divided into five groups (control, DMSO, CDDP (7.5 mg/kg), CDDP + PVE (25 mg/kg), and CDDP + PVE (50 mg/kg)). Biochemical and histopathological analyses were then performed. Rutin, gallic acid, p-coumaric acid and protocatechuic acid were identified as major components of PVE. Total antioxidant status and glutathione (GSH) values increased significantly in the serum samples from the treatment group compared to the CDDP group, while blood urea nitrogen, creatinine, oxidative stress index, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), total oxidant status, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) values decreased significantly. GSH levels increased significantly in the treatment group compared to the CDDP group, while TNF-α, caspase-3, 8-OHdG, MDA levels and damage scores decreased significantly. In conclusion, PVE exhibited strong protective effects through its anti-apoptotic, antioxidant, and anti-inflammatory activities against nephrotoxicity and oxidative damage caused by CDDP in rats.

An Investigation of the Antiproliferative Effect of Rhododendron luteum Extract on Cervical Cancer (HeLa) Cells via Nrf2 Signaling Pathway.

The aim of the present study was to investigate the role of Rhododendron luteum extract (RLE) in the induction of Nrf2­related oxidative stress and endoplasmic reticulum (ER) stress in human cervical cancer (HeLa) cells. The antiproliferative effect of RLE on HeLa and fibroblast cells was determined using the MTT assay. The effects of RLE on the cell cycle, apoptosis, and production of reactive oxygen species (ROS) in HeLa cells were evaluated using fluorescent probes. The mRNA expression levels of Nrf2 [and its targets glutamate-cysteine ligase catalytic subunit (GCLC), and glucose-6-phosphate dehydrogenase (G6PD)], and C/EBP homologous protein (CHOP, an ER stress marker were determined using reverse transcription­quantitative polymerase chain reaction (RT-PCR). The results demonstrated that RLE exhibited a selective cytotoxic effect (2.9-fold) on HeLa cells compared to fibroblast cells. RLE arrested the cell cycle at the S phase, and induced apoptosis, ER stress, and ROS formation. In addition, RLE significantly suppressed the expression levels of Nrf2, GCLC and G6PD (0.65, 0.69, and 0.54-fold, respectively) and increased the expression of CHOP (4.48-fold) in HeLa cells at 72 h of treatment (p < 0.05). These results show that the antiproliferative effect of RLE occurs through the Nrf2 and ER stress pathways, and the results should now be supported by further in vivo studies.

Suppression of cisplatin-induced ovarian injury in rats by chrysin: an experimental study.

The aim of this study was to investigate the potential therapeutic efficacy of chrysin (CHS) against ovotoxicity caused by intraperitoneal administration of cisplatin (CDDP) in rats. In this experimental study, 24 female rats were randomly divided into four groups: control, CHS (2 mg/kg), CDDP (5 mg/kg) and CDDP (5 mg/kg) + CHS (2 mg/kg). The levels of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), interleukin-6 (IL-6) and myeloperoxidase (MPO) were determined in the ovarian tissues using spectrophotometric methods. In addition, the ovarian samples were evaluated histopathologically by hematoxylin&eosin staining. The results revealed that the levels of MDA, TOS, IL-6 and MPO significantly increased by CDDP administration compared with control group (p < 0.05). Also, it was found that CDDP significantly decreased TAS and SOD levels (p < 0.05). CHS ameliorated CDDP-induced the increased levels of MDA, TOS, IL-6, MPO and increased the levels of TAS and SOD significantly (p < 0.05). Histological findings also supported the therapeutic effect of CHS against CDDP-induced ovarian damage parameters. In conclusion, our results showed that CHS exhibits a therapeutic effect against CDDP-induced ovotoxicity and therefore the use of CHS after chemotherapy may improve the side effets of CDDP. IMPACT STATEMENTWhat is already known about this subject? Cisplatin (CDDP) is an effective and widely used chemotherapeutic agent to treat various malignancies, but its therapeutic use is limited due to dose-related tissue toxicity. Chrysin (CHS), a natural flavone, exhibits various beneficial activities, including antioxidant, anti-inflammatory and anticancer. There are increasing evidences in the literature that CHS reduces the toxicity of various chemotherapeutic agents, such as CDDP, doxorubicin and cyclophosphamide, in colon, kidney and liver tissues through its antioxidant and anti-inflammatory potential.What do the results of this study add? This study demonstrated that CHS can abolish CDDP-induced in vivo ovarian injury by decreasing MDA, TOS, IL-6 and MPO levels and increasing SOD and TAS levels through its antioxidant and anti-inflammatory potential.What are the implications of these findings for clinical practice and/or further research? This study revealed the therapeutic potential of CHS against CDDP-induced acute ovotoxicity, for the first time. Further pre-clinical studies are necessary to prove the beneficial effect of CHS on the prevention of CDDP-induced ovarian toxicity.

Biomarker potentials of miRNA-associated circRNAs in breast cancer (MCF-7) cells: an in vitro and in silico study.

Breast cancer is a heterogeneous disease, which is the most common malignancy in women. The incidence and mortality rates of breast cancer indicate that it is the leading cause of cancer-related with deaths. circRNAs operate as part of competing endogenous RNAs (ceRNAs) mechanisms, which play critical roles in the different biological processes of breast cancer such as proliferation, migration, and apoptosis. The goal of the present study is to identify the potential predictive biomarker for breast cancer diagnosis in the circRNA network by in vitro and in silico analyzes. 40 miRNAs were obtained from the miRWalk database and their combinatorial target genes (potential ceRNAs) were identified with ComiR. We stated that the cancer-specific circRNA genes in MCF-7 cells using the cancer-specific circRNA (CSDC) database, and obtained the ones showing potential ceRNA activity in our previous analysis among them. Identified genes with remarkable expression differences between BCa and normal breast tissue were determined by the GEPIA database. Moreover, the Spearman correlation test in the GEPIA database was used for the statistical analysis of the relationship between DCAF7 and SOGA1, SOGA1 and AVL 9, DCAF7 and AVL 9 gene pairs. And also, DCAF7, SOGA1, and AVL9 gene expression levels were detected in MCF-7 and MCF-10A cells by RT-qPCR method. DCAF7, SOGA1, and AVL9 gene were significantly more expressed to BCa tissue and MCF-7 cells than normal breast tissue and MCF-10 A cells. And also, DCAF7 and SOGA1, SOGA1 and AVL9, DCAF7 and AVL9 genes pairs were found to be significantly correlated with BCa. These genes may be considered as potential predictive biomarkers to discriminate BCa patients from healthy persons. Our preliminary results can supply a new perspective for in vitro and vivo studies in the future.

Reference change value and measurement uncertainty in the evaluation of tumor markers.

The use of measurement uncertainty among clinical laboratories becomes widespread. Measurement uncertainty can be reported with the result, as well as be used in certain reference change value (RCV) calculation equations. RCV is especially recommended for use in tests with a low individuality index. In our study, we calculated the measurement uncertainty of AFP, CA 125, CA 15-3, CA 19-9, CEA tumor markers with the ISO TS 20914:2019. We compared results with limits. Two Beckman Coulter DXI-800 (Minnesota, USA) autoanalysers' results were used. We calculated the RCV values using the classical Fraser method, logarithmic Lund Method, and Clinical Laboratory Standards Institute (CLSI) method as Minimal Difference (MD). We found the same permissible measurement uncertainty limit as 15.97% for all five tumor markers. The highest RCV value was found as 90% upstream for AFP test with Lund logarithmic approach, the lowest RCV value was found as 12% for CEA with MD, all other RCV results were between these two values. We do not recommend the use of MD, as values for Biological variation are not used in the MD approach. We also recommend using the logarithmic approach, although it gives higher results. There are also clinical studies on the significance of tumor markers in a follow-up that show different results. These differences may be because the studies are conducted with different systems. Therefore, each laboratory needs to calculate its own RCV values. We also recommend informing the clinicians about the tests with high measurement uncertainty.

Effect of Turkish Propolis on miRNA Expression, Cell Cycle, and Apoptosis in Human Breast Cancer (MCF-7) Cells.

Enriched in flavonoid compounds, phenol acids, and terpene derivatives, propolis has been shown to regulate apoptosis signaling pathways and alter the expression of microRNAs (miRNAs). In the present study, it has been aimed to examine the effects of Turkish propolis on miRNA levels of breast cancer (MCF-7) cells, and its relationship with cell proliferation and apoptosis. Cytotoxic activity of ethanolic propolis extract (EEP) was evaluated using MTT assay. Mechanisms involved in the cytotoxic action of Turkish propolis in MCF-7 cells were investigated with regard to apoptosis and cell cycle using flow cytometry and western blot. Mitochondrial membrane potential (MMP) were evaluated by spectrofluorometric method. miRNA levels were detected by qRT-PCR method. EEP exhibited selective toxicity against MCF-7 cells compared to normal fibroblast cells. EEP increased the cell cycle arrest at the G1 phase. EEP elevated the apoptotic cell death through increasing pro-apoptotic protein levels (p21, Bax, p53, p53-Ser46, and p53-Ser15), decreasing MMP and altering the expression levels of specific tumor suppressors (miR-34, miR-15a, and miR-16-5p) and oncogenic (miR-21) miRNAs. These data support that Turkish propolis may be evaluated as a potential natural agent for new anticancer drugs in future.

Rosa canina Extract has Antiproliferative and Proapoptotic Effects on Human Lung and Prostate Cancer Cells.

Although several studies have investigated the cytotoxic effects of different Rosa species, there has been only limited research into the cytotoxic effect of Rosa canina. The purpose of this research was to evaluate the antioxidant properties, phenolic characterization, and cytotoxic effects of R. canina on human lung (A549) and prostate (PC-3) cancer cells and the possible mechanisms involved. The antioxidant properties and phenolic characterization of the extract were determined using spectrophotometric methods and RP-HPLC, respectively. The cytotoxic activity of the extract was determined using the MTT assay. The mechanism involved in the extract's cytotoxic effect was then evaluated in terms of apoptosis, the cell cycle, mitochondrial membrane potential (MMP), and caspase activity using fluorometric and luminometric methods. The TPC value of the extract was 58.97 ± 2.22 mg gallic acid equivalents per gram sample, and ascorbic acid and p-coumaric acid were detected as major phenolics in the extract. R. canina extract exhibited a selective cytotoxic effect on A549 and PC-3 cells compared to normal fibroblast cells. The extract induced cell cycle arrest at the G1 phase and apoptosis via reduced MMP and increased caspase activity in these cells. Phytomedical applications of R. canina may represent promising approaches in the treatment of cancer.

Dorycnium pentaphyllum Extract Has Antiproliferative Effect on Human Cervix and Colon Cancer Cells.

Although several studies have investigated the cytotoxic effects of different Fabaceae species, limited researches have been conducted on the cytotoxic effect of Dorycnium pentaphyllum. The aim of this study was to evaluate the phenolic characterization and the cytotoxic effect of D. pentaphyllum on human cervix (HeLa) and colon (WiDr) cancer cells and the possible mechanisms involved. Total phenolic content (TPC) and phenolic characterization of the extract were investigated using the Folin-Cioceltau method and RP-HPLC, respectively. The cytotoxic effect of the extract was evaluated using the MTT assay. The mechanism involved in the extract's cytotoxic effect was then evaluated in terms of apoptosis and the cell cycle using flow cytometry, while mitochondrial membrane potential (MMP) was investigated using the fluorometric method. The TPC value of the extract was 141.2 ± 0.8 mg gallic acid equivalent per g sample, and quercetin was detected as major phenolics. D. pentaphyllum extract exhibited a selective cytotoxic effect on HeLa and WiDr cells compared to normal fibroblast and colon cells, respectively. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in these cells. Further studies may be useful in developing a natural product based new generation pharmacological agent.

Dimethyl Sulfoxide Extract of Dianthus carmelitarum Induces S Phase Arrest and Apoptosis in Human Colon Cancer Cells.

Although several studies have investigated the cytotoxic effects of different Dianthus species, there has been only limited research into the cytotoxic effect of Dianthus carmelitarum. The purpose of this research was to evaluate the phenolic characterization and the cytotoxic effect of D. carmelitarum on human colon cancer (WiDr) cells and the possible mechanisms involved. Total polyphenolic contents (TPC) and phenolic characterization of the extract were evaluated using the Folin-Cioceltau method and reversed-phase high performance liquid chromatography (RP-HPLC), respectively. The cytotoxic activity of the extract was determined using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. The mechanism involved in the extract's cytotoxic effect was then evaluated in terms of apoptosis and the cell cycle using flow cytometry, while mitochondrial membrane potential (MMP) was investigated using the fluorometric method. The TPC value of the extract was 784.8 ± 40.3 mg gallic acid equivalent per 100 g sample, and sinapic acid and benzoic acid were detected as major phenolics in the extract. D. carmelitarum extract exhibited a selective cytotoxic effect (3.6-fold) on WiDr cells compared to normal colon cells. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in WiDr cells. Phytomedical and nutraceutical applications of D. carmelitarum may represent promising approaches in the treatment of cancer.

Morus Rubra Extract Induces Cell Cycle Arrest and Apoptosis in Human Colon Cancer Cells Through Endoplasmic Reticulum Stress and Telomerase.

Many studies have reported cytotoxic effects of different Morus species, but there have been only limited studies on the cytotoxic effect of Morus rubra. The aims of this study were to evaluate the cytotoxic effect of dimethyl sulfoxide extract of M. rubra and to investigate, for the first time, its probable cytotoxic activity in human colon cancer (WiDr) cells, together with the mechanism involved. The cytotoxic activity of extract was determined using MTT assay. The mechanism involved in the cytotoxic effect of extract was then evaluated in terms of apoptosis, and the cell cycle using flow cytometry, mitochondrial membrane potential (MMP) was investigated using the fluorometric method, and expression levels of telomerase and C/EBP homologous protein (CHOP) were investigated using reverse-transcription PCR (RT-PCR). M. rubra extract exhibited moderate selective cytotoxicity on colon cancer cells compared with fibroblast cells. Extract induced cell cycle arrest at the G1 phase and apoptosis via reduced MMP in WiDr cells. Additionally, M. rubra extract significantly repressed telomerase and induced CHOP expressions in WiDr cells. Our results demonstrate that targeting telomerase and endoplasmic reticulum stress represents a promising strategy in colon cancer therapy, and M. rubra may have considerable potential for development as a novel natural product-based anticancer agent.

Antiproliferative and apoptotic effect of Morus nigra extract on human prostate cancer cells.

Background: Morus nigra L. belongs to the family Moraceae and is frequently used in traditional medicine. Numerous studies have investigated the antiproliferative effects of various extracts of different Morus species, but studies involving the in vitro cytotoxic effect of M. nigra extract are very limited. The purpose of this study was to evaluate the phenolic composition and antioxidant activity of dimethyl sulfoxide extract of M. nigra (DEM) and to investigate, for the first time, the probable cytotoxic effect in human prostate adenocarcinoma (PC-3) cells together with the mechanism involved. Methods: Total polyphenolic contents (TPC), ferric reducing antioxidant power (FRAP) and phenolic compounds of DEM were evaluated using spectrophotometric procedures and HPLC. The cytotoxic effect of DEM on PC-3 cells was revealed using the MTT assay. Mechanisms involved in the cytotoxic effect of DEM on PC-3 cells were then investigated in terms of apoptosis, mitochondrial membrane potential and cell cycle using flow cytometry, while caspase activity was investigated using luminometric analysis. Results: TPC and FRAP values were 20.7 ± 0.3 mg gallic acid equivalents and 48.8 ± 1.6 mg trolox equivalents per g sample, respectively. Ascorbic acid and chlorogenic acid were the major phenolic compounds detected at HPLC analysis. DEM arrested the cell cycle of PC-3 cells at the G1 phase, induced apoptosis via increased caspase activity and reduced mitochondrial membrane potential. Conclusions: Our results indicate that M. nigra may be a novel candidate for the development of new natural product based therapeutic agents against prostate cancer.

Antiproliferative and proapoptotic activity of Turkish propolis on human lung cancer cell line.

Cancer is a heterogeneous disease, two of whose characteristic features are uncontrollable cell proliferation and insufficient apoptosis. Various studies have investigated the antiproliferative effects of propolis, a natural bee product, from different countries, and its cytotoxic effects have been attributed to its polyphenol contents. The purpose of this study was to show the cytotoxic effects, and possible mechanisms involved, of ethanolic extract of Turkish propolis (EEP) on the human lung cancer (A549) cell line. Cytotoxic activity of EEP on A549 cells was revealed using the MTT assay. Mechanisms involved in the cytotoxic action of EEP on A549 cells were then investigated in terms of apoptosis, mitochondrial membrane potential and cell cycle using flow cytometry, endoplasmic reticulum stress using RT-PCR, and caspase activity using luminometric analysis. EEP exhibited selective toxicity against A549 cells compared to normal fibroblast cells. We determined that EEP arrested the cell cycle of A549 cells at the G1 phase, induced endoplasmic reticulum stress, caspase activity, and apoptosis and reduced mitochondrial membrane potential. These results indicate that Turkish propolis is capable of reducing cancer cell proliferation and may have a promising role to play in the development of new anticancer drugs in the future.

Positive correlation between insulin resistance and iron overload-induced oxidative stress in patients with fanconi anemia (FA)- and non-FA-related bone marrow failure: The results of a multicenter study.

This study investigated the relationship between DNA, protein, and lipid oxidations and insulin resistance in patients with Fanconi anemia (FA)- and non-FA-related bone marrow failure. Sixteen patients with FA, 7 non-FA-related aplastic anemia, and 10 controls were included in the study. Fasting blood glucose, simultaneous insulin, hepcidin, ferritin, 8-hydroxy deoxyguanosine (8-OHdG), protein carbonyls, malondialdehyde (MDA), and homeostatic model assessment-insulin resistance (HOMA-IR) were investigated in the patients and controls. Diepoxybutane test-positive (DEB+) patients were diagnosed with FA, whereas DEB-patients were diagnosed as non-FA. 8-OHdG levels in both FA and non-FA patients were significantly higher than those in the controls (P = .001 and P = .005, respectively). Serum ferritin levels were also higher in FA and non-FA patients than in the controls (P = .0001 and P = .005, respectively). Insulin resistance (IR) was significantly higher in FA patients than in non-FA patients and controls (P = .005 and P = .015, respectively). Significant differences were observed between 8-OHdG, ferritin, and MDA levels in patients with or without IR (P = .009, P = .001, and P = .013, respectively). Moderate and strong relations of 44% and 85% were determined between IR and ferritin levels in patients with FA or non-FA (P = .08 and P = .014, respectively). FA and non-FA patients exhibited a tendency to IR. IR was related to ferritin levels, and ferritin levels were also correlated with oxidative stress. These findings suggest that the increased rate of IR in patients with FA and non-FA may derive from increased oxidative stress, which may in turn be due to elevated serum ferritin levels.

Selective cytotoxic effect of Rhododendron luteum extract on human colon and liver cancer cells.

PURPOSE: The genus Rhododendron is distributed entirely in the world with the exception of South and Central America and Africa, growing in a large diversity of climatic conditions. This genus is a rich source of phenolic compounds, especially flavonoids, essential oils, chromones, terpenoids, and steroids. It has many biological properties such as antioxidant, anti-inflammatory, antiviral, antibacterial, anticancer, antidiabetic, immunomodulatory, cardioprotective and hepatoprotective among others due to their polyphenolic constituents. The objective of the current study was to evaluate the antioxidant properties and cytotoxic activity of dimethyl sulfoxide extract of flowers of Rhododendron luteum (DEFR) for the first time. METHODS: The total polyphenolic contents (TPC), total flavonoid contents (TFC) and ferric reducing antioxidant power (FRAP) of the extract were evaluated using spectrophotometric procedures. The cytotoxic activity of the extract on three cancers (human breast, colon and liver carcinoma) and human foreskin fibroblast cells was determined using the MTT assay. RESULTS: TPC and FRAP values were found 54.2±0.38 mg gallic acid equivalents and 164.2±1.77 mg trolox equivalents per to g sample, respectively. R.luteum extract exhibited selective cytotoxicity against colon and liver cancer cells compared to normal fibroblast cells, while this selective cytotoxicity was not observed in breast cancer cells. CONCLUSION: Our results demonstrate that the Rhododendron luteum may be a great source of antioxidant and antitumor natural agents due to their capability of decreasing cancer cells proliferation.

Alpha-pinene neutralizes cisplatin-induced reproductive toxicity in male rats through activation of Nrf2 pathway.

PURPOSE: Testicular toxicity is one of the most important side effects of cisplatin (CP) therapy. Alpha-pinene (AP) is a naturally occurring monoterpene with antioxidant character in plants. Here, we aimed to evaluate the therapeutic activity of AP against CP-induced testicular toxicity by including the nuclear factor erythroid 2-associated factor 2 (Nrf2) pathway in rats. METHODS: Thirty male rats were divided into 5 groups: control, CP, CP + AP (5 and 10 mg/kg) and only AP (10 mg/kg). CP was administered intraperitoneally at a dose of 5 mg/kg on the first day, followed by three consecutive injections of AP. Serum reproductive hormone levels were evaluated using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers in testicular tissue were also determined colorimetrically. In addition, how CP affects Nrf2 pathway and the effect of AP on this situation were also addressed. RESULTS: Treatment with CP significantly increased OS, inflammation, ERS and apoptosis in testicular tissue. Administrations of AP resulted in an amelioration of these altered parameters. The mechanism of therapeutic effect of AP appeared to involve induction of Nrf2. Furthermore, these results were also confirmed by histological data. CONCLUSION: Results suggest that AP can exhibit therapeutic effects against CP-induced testicular toxicity. It can be concluded that AP may be a potential molecule to abolish reproductive toxicity after chemotherapy.

Gallic acid attenuates torsion/detorsion-induced testicular injury in rats through suppressing of HMGB1/NF-κB axis and endoplasmic reticulum stress.

It was aimed to evaluate whether gallic acid (GA) have a beneficial effect in the testicular ischemia/reperfusion injury (IRI) model in rats for the first time. Testicular malondialdehyde, 8-hydroxy-2'-deoxyguanosine, superoxide dismutase, catalase, high mobility group box 1 protein, nuclear factor kappa B, tumor necrosis factoralpha, interleukin-6, myeloperoxidase, 78-kDa glucose-regulated protein, activating transcription factor 6, CCAAT-enhancer-binding protein homologous protein and caspase-3 levels were determined using colorimetric methods. The oxidative stress, inflammation, endoplasmic reticulum stress and apoptosis levels increased statistically significantly in the IRI group compared with the sham operated group (p < 0.05). GA application improved these damage significantly (p < 0.05). Moreover, it was found that the results of histological examinations supported the biochemical results to a statistically significant extent. Our findings suggested that GA may be evaluated as a protective agent against testicular IRI.

Effects of glucosamine sulfate and exercise therapy on serum leptin levels in patients with knee osteoarthritis: preliminary results of randomized controlled clinical trial.

Osteoarthritis (OA) is a slow, chronic disease characterized by the focal deterioration and abrasion of articular cartilage. Leptin may play an important role in the pathophysiology of OA. Exercise and glucosamine sulfate therapy is one of the most commonly used in patients with knee OA. The goals of the present study are performed to investigate whether 12-week strength training program and glucosamine sulfate have an effect on serum leptin levels in knee OA and the relationship between leptin, clinical parameters, and radiographic severity of knee OA. Thirty-seven women with the diagnosis of knee OA were enrolled in the study. Patients were randomized into two groups. Group I (n = 19) received an exercise program, while group II (n = 18) received glucosamine sulfate (1,500 mg/day) in addition to the exercise therapy. Both groups were treated for 12 weeks. Leptin level was assessed at baseline and after 12 weeks. The concentration of leptin was measured by ELISA. The patients were evaluated regarding pain, disability, functional performance, and muscle strength. Both groups showed significant improvements in leptin levels, pain, disability, muscle strength, and functional performance with no statistically significant difference between the groups after the therapy. At basal time, plasma leptin levels were significantly correlated with body mass index and duration of disease, but no significant correlation was found with patient age, pain, disability, functional performance, muscle strength, and radiographic severity of knee OA. The results of this preliminary study revealed that exercise alone was adequate to prevent structural changes relieving the symptoms of OA. We also found that exercise alone could affect serum plasma levels of the leptin, important mediators of cartilage metabolism. Decreases in serum leptin may be one mechanism by which cartilage metabolism affects physical function and symptoms in OA patients.

Lack of significant difference between internal spermatic vein and brachial vein ischemia modified albumin levels in patients with varicocele.

Varicocele is the most common and surgically correctible cause of male infertility in men attending to infertility clinics. Infertility affects 15% of all couples and male factor is the primary or contributing cause in 40% to 60% of cases. Varicocele has been shown to cause male infertility in about 15% of infertile couples. Molecular mechanisms responsible from varicocele induced testicular dysfunction and male infertility have not been completely unknown. Recent years have witnessed a huge amount of scientific works devoted to the mechanism of varicocele associated male infertility and rapid progress in research on its cellular and molecular mechanisms, including apoptosis and oxidative stress of germ cells. Here we evaluated internal spermatic vein and brachal vein ischemia modified albumin (IMA) level in 40 adult male patients with varicocele. IMA level was analyzed using albumin cobalt-binding test. Spermatic vein and brachial vein IMA levels were 0.381 ± 0.135 ABSU (absorbance units) and 0.385 ± 0.131 ABSU, respectively. There was no statistically significant difference between the two areas. IMA levels in the internal spermatic vein of patients with varicocele should not be used as a marker of hypoxia.