Protective role of resveratrol on testicular germ cells in mice with testicular toxicity

WOS: 000416270600010Objective: The aim of the present study was to investigate the possible beneficial effects of resveratrol in mice subjected to vinyl cyclohexene dieposide (VCD) -induced testicular toxicity. Material and methods: A total of thirty-six Swiss albino male mice aged 28-days were used in the present study. The study was composed of two stages where mice which received or did not receive VCD (320 mg/kg/day) were administered resveratrol. The animals were assigned into control and resveratrol-treated groups in the first stage and into groups of VCD- and VCD+resveratrol-treated groups in the second stage. At the end of the experiments, relative testicular weight (TW/BW) and dry/wet weight of testis (TDW/TWW) were calculated. Histological analysis by hematoxylin and eosin (H&E) staining and immunohistochemical staining by BAX and Bcl-2 were performed. Serum testosterone, LH and FSH levels were measured by a commercially available ELISA kit. Results: Resveratrol caused a dose-dependent increase in TW/BW and decrease in TDW/TWW (p<0.05). Resveratrol at a dose of 20 mg/kg resulted in an improvement in testosterone, LH and FSH levels in mice with VCD-induced testicular toxicity (p<0.001). Resveratrol also improved apoptotic index and epithelial cell height of testicular seminipherous tubuli significantly after VCD exposure (p<0.001). Conclusion: Results of the present study suggest that resveratrol can be used as a protective and/or therapeutic agent particularly for cases with male infertility caused by testicular toxicity

The therapeutic potential of amifostine on cyclophosphamide-induced testicular dysfunction in rats: An experimental study

Background: Cyclophosphamide (CP) is a well-known alkylating anticancer agent used in the treatment of various malignant and non-malignant tumors. CP may also cause a variety of adverse effects, including reproductive toxicity. Amifostine is known as a cytoprotective drug having antioxidant properties. Objective: To evaluate the possible beneficial effects of amifostine on testicular toxicity induced by CP in rats. Materials and Methods: A total of 35 Sprague-Dawley rats were used in this experimental study. The CP group animals received a single dose of 200 mg/kg CP on Day 8 by intraperitoneal injection and were left untreated for the following seven days. The two remaining groups of animals were treated with 200 mg/kg/day amifostine (AMF 200) and 400 mg/kg/day amifostine (AMF 400) for seven days prior to and following a single intraperitoneal injection of CP. Morphometrical analysis and histological examination of testicular tissue were performed. Serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels were measured in serum using commercial ELISA kits. The epidydimal sperm count was determined. Results: The tubular epithelial height in the testis was significantly higher in the AMF400 group compared to other groups (p &lt; 0.001). Animals in the AMF400 group showed minimal debris in the tubules, no Sertoli cell damage, and the Johnsen scores were slightly higher in the AMF400 group. The epididymal sperm count was significantly lower in the CP-administered animals compared to the control animals and was significantly higher in the AMF200 and AMF400 groups compared to the CP group (p = 0.006, and p = 0.019 respectively). Conclusion: Amifostine, at a dose of 400 mg/kg, may have a protective effect on testicular damage induced by CP in rats

Ameliorative impacts of floral extract of Salvia species on oxidative stress and inflammation in rats renal ischemia/reperfusion

91-100I/R injury is a potentially serious problem that is encountered during a variety of medical and surgical procedures, such as thrombolytic therapy, organ transplantation and coronary angioplasty, The basic pathophysiology of I/R injury is microvascular dysfunction which is developed following reperfusion of ischemic tissues. It has clinical importance because of its frequent occurrence and mortality in some surgical conditions such as renal transplantation. Here, we investigated the protective effect of Salvia extracts on kidneys against I/R injury. Forty Spraque Dawley rats were divided into 5 groups. Right nephrectomy was performed to all groups. Gr. I, control; Gr. II, I/R; Gr. III & IV, I/R+50 and I/R+100 mg/kg Salvia floral extract; and Gr. V with I/R+50 mg/kg Rosmarinic acid. Salvia and Rosmarinic acid for 7 days was given single dose as a gavage.60 min ischemia, 60 min reperfusion were applied to groups except control. Intracardiac blood samples were taken, Blood urea nitrogen, creatine, malondialdehyde, myeloperoxidase, nitric oxide and chitotriosidase levels were detected. Mean values were evaluated by statistical analysis. The renal tissues were examined under light microscopy. Based on our biochemical and histological data, Salvia floral extract has potent anti-inflammatory and antioxidant effects against renal structure and function

Effects of hydrogen sulfide on acetaminophen-induced acute renal toxicity in rats

Introduction and aim Hydrogen sulfide (H2S) is an endogenously produced gas-structure mediator. It is proposed to have antioxidant, anti-inflammatory and antiapoptotic effects. Acetaminophen (N-acetyl-P-aminophenol; APAP) is an antipyretic and analgesic medication known as paracetamol. When taken at therapeutic doses there are few side-effects, but at high doses APAP can cause clear liver and kidney damage in humans and experimental animals. In this study, the effects of the H2S donor of sodium hydrosulfide (NaHS) on acute renal toxicity induced by APAP in rats were researched in comparison with N-acetyl cysteine (NAC)

Estrogen-like Activity of Quercetin in Female Rats

WOS: 000383612800002Objective: Quercetin is a phytoestrogen that exerts both in vitro agonistic and antagonistic activities on estrogen receptors. The present study evaluated the in vivo estrogen-like activity of quercetin on the reproductive organs of female rats. For this purpose, a partial estrogen agonist tamoxifen (TMX) and an estrogen antagonist fulvestrant (FLV) were used to mimic and antagonize the effects of estrogen on uterine tissue, respectively. 4-Vinylcyclohexene dioxide (VCD) was used to induce primary ovarian failure in rats. Materials and Methods: In experiment 1, immature female rats (21-22 days old) were treated with a vehicle (control), quercetin (10, 30, and 90 mg/kg), 10 mg/kg of quercetin (Q10)+TMX, Q10+FLV, 17 beta-estradiol (17 beta E), 17 beta E+TMX, or 17 beta E+FLV. In experiment 2, prepubertal female rats (28-29 days old) were treated with a vehicle (dimethyl sulfoxide), VCD-alone, VCD+Q10, or VCD+17 beta E. A uterotrophic assay and histological analysis of uteri were performed. The partial estrogen agonist TMX and the estrogen antagonist FLV were used to mimic and antagonize the effects of estrogen on uterine tissue, respectively. VCD was used to induce primary ovarian failure in rats. Results: In immature female rats, the uterine weight was significantly higher in animals treated with Q10 compared to those treated with the vehicle. Although TMX did not result in a significant change, FLV significantly decreased the uterine weight in Q10-treated rats. In prepubertal female rats, the uterine weight significantly decreased in VCD +/- Q10- or 17 beta E-treated animals compared that in VCD-treated animals. Although the endometrial thickness was unchanged in Q10-treated animals, it was significantly decreased in the Q10+FLV-treated animals. VCD significantly decreased the endometrial thickness, which was prevented by Q10. Conclusion: Quercetin may have a dose-dependent and biphasic effect on the uterus by modulating estrogen receptors

The effects of recombinant klotho in cisplatin-induced ovarian failure in mice

© 2021 Japan Society of Obstetrics and GynecologyAim: To investigate whether recombinant klotho given concomitantly with cisplatin is effective in preventing cisplatin-induced ovarian damage. Methods: Thirty-two adult female mice were divided into four groups. Saline was given to the first group, cisplatin to the second group, recombinant mouse klotho to the third group, and recombinant mouse klotho + cisplatin to the fourth group. The removed ovarian tissues were examined and groups were compared histologically and immunohistochemical examination for antimullerian hormone (AMH), superoxide dismutase (SOD) and catalase expression were done. Glutathione peroxidase (GPx) and glutathione reductase (GR) activities were measured by ELISA. Results: Ovarian tissue weight, primary and secondary follicle counts were higher in cisplatin + recombinant klotho group compared to cisplatin group in our study (respectively p 0.05). AMH staining intensities were similar between cisplatin and cisplatin + recombinant klotho groups (p = 0.925). There was no difference between the groups in terms of SOD, GPx, and GR (p > 0.05). Conclusions: The recombinant klotho administered before cisplatin could partially protect the ovarian tissue from cisplatin-induced ovarian damage considering that there was no difference in histologic injury score parameters, AMH staining intensity and oxidative stress markers between cisplatin and cisplatin plus klotho groups except that klotho preserved follicules to some extent. The antioxidant mechanism of action of klotho may not be the primary protection mechanism in cisplatin induced ovarian injury

Enhancement of vascular endothelial growth factor's angiogenic capacity by the therapeutic modulation of notch signalling improves tram flap survival in rats submitted to nicotine

WOS: 000417955500006PubMed ID: 28277073Background: Smoke of cigarettes, and specifically nicotine, has been shown to diminish pedicled transverse rectus abdominis musculocutaneous (TRAM) flap survival. Considering that Notch signalling through its ligand Delta-like 4 (Dll4) functions as anti-angiogenic factor by inhibiting the pro-angiogenic effects of vascular endothelial growth factor (VEGF), it is hypothesised that inhibition of the Notch would promote angiogenesis and increase TRAM flap survival in rats submitted to nicotine. Methods: Twenty rats were treated with nicotine for 28 days preoperatively. Thereafter, a pedicled TRAM flap was created in all animals. The Notch inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine-t-butyl-ester was administered in animals of the treatment group. Animals in the control group were given the same amount of solvent. Five days after the surgery, viable flap areas were determined. Skin samples were evaluated for VEGF and Dll4 mRNA levels. Immunohistochemical analysis was used for the assessment of endothelial Dll4 expression. Vascular density was determined histologically. Plasma levels of VEGF and Dll4 were measured. Results: A significant improvement in TRAM flap surviving area was observed in the treatment group (53.5014.25%) compared with the controls (32.20 +/- 9.15%). Immunohistochemical analysis revealed a significant increase in the number of Dll4 stained vessels in animals of the treatment group (9.2 +/- 1.6) in comparison with the controls (5.7 +/- 1.9). VEGF mRNA levels (0.22 +/- 0.08) in the treatment group were significantly lower than those in the control group (0.36 +/- 0.09). Conclusion: Notch inhibition significantly improved TRAM flap survival in animals exposed to nicotine by promoting VEGF-induced angiogenesis.Ahi Evran University Research FundAhi Evran UniversityThis study was approved by the Ethical Committee for Experimental Research on Animals and supported by Ahi Evran University Research Fund

The effect of sperm activation on pinopod formation in endometrial epithelium

WOS: 000393053300002Introduction: Endometrial receptivity is crucial in implantation of the developing embryo in the endometrium and formation of the pregnancy. In this study, possible effect of sperm and uterine endometrial contact on formation of pinopod, an important element in morphological differentiation necessary for implantation, was investigated. Materials and methods: In this experimental study, 42 female Spraque-Dawley albino rats and 14 male Spraque-Dawley albino rats (total 56 rats) were used. Vasectomy was performed in half of the male rats. For each group, two distinct branches were formed with 21 females and 7 males: Group 1 (non-vasectomized) and Group 2 (vasectomized). Cases were sacrificed and evaluated every day from Day 1 to Day 3. Scanning electron microscopic (SEM) images were analyzed according to different stages of pinopod development on different days. Pinopods were classified as developing, developed and regressing pinopod. The average number of pinopods were calculated by counting the pinopods at four endometrial regions examined for each rat and total number was divided by 4. Same procedure was done for all rats in every group. Results were compared among the groups. For statistical analysis among the groups, *Independent Samples Test (Mean +/- Std) and **Mann Whitney U Test (Median (25-75%)) were used. Results: The most important finding in SEM examination of uterus removed on the first day following mating from female rats that were copulated with non-vasectomy male rats which comprised the first group of the study was that heads of the sperms in the uterus were embedded in endometrial epithelium. Similarly, examination of the endometrium of uterus that were removed on postcoital second day revealed small number of developed pinopods (average 0.39) (P = 0.902). Examination was done by taking the developing pinopods within image area into account and number of developing pinopods in endometrium epithelium of the rats in first group (average 20.61) was higher than that of second group (average 12.86) (P < 0.001). Examination of endometrium of the uterus that were removed on third postcoital day revealed less number of developing pinopods in both groups. Examination of first group revealed an average of 1.21 developing pinopod, whereas the average number of developing pinopod in second group was 2.25 (P = 0.011). Examination based on the count of developed pinopods revealed that number of pinopods in first group (average 13.79) was higher than second group (average 8.96) (P < 0.001). Regressing pinopod images were observed in only endometrium that were taken on postcoital third day in the second group. Discussion: In this study, it was clearly shown that sperms were entered into endometrial epithelium with their heads. It can be suggested that they might have a facilitating effect for pinopod formation by reacting with endometrial epithelium as a result of this invasion. It would be beneficial to demolish the other factors triggering pinopod formation to investigate whether presence of sperm alone in the uterus has an effect on pinopod formation. (C) 2016 Anatomical Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved

Cisplatin decreases HOXA13 and alphaVBeta3 integrin levels in the uterus.

© 2021Objective: To examine the effects of cisplatin on uterine histology and implantation molecules and the possible protective role of recombinant Klotho administration on uterine histology and uterine receptivity in mice exposed to cisplatin. Materials and methods: This study was conducted using thirty-two adult female mice assigned to four groups with 8 mice in each group. Saline was given to the 1st group, cisplatin to the 2nd group, recombinant mouse Klotho to the 3rd group and recombinant mouse Klotho plus cisplatin to the 4th group. Uterine tissues were examined for damage histologically and immunobiologically for the uterine receptivity markers HOXA13 and alphaVBeta3 integrin. Results: Apoptosis, degeneration, decrease in uterine thickness and uterine absence of gland scores were higher in the cisplatin group (3rd group) compared to the saline group (1st group) (cisplatin vs. saline p < 0.0001 for all parameters). In the recombinant Klotho plus cisplatin group (4th group), scores of apoptosis, degeneration, reduction in uterine thickness and uterine absence of gland were lower than the group receiving only cisplatin (cisplatin plus recombinant Klotho vs cisplatin, p = 0.006 for apoptosis; p = 0.017 for degeneration; p = 0.011 for the reduction in uterine thickness; p = 0.002 for the absence of gland). However, HOXA13 and alphaVBeta3 integrin staining levels were not different between the cisplatin group (group 3) and the cisplatin plus recombinant Klotho group (group 4) (p = 0.980 and p = 0.762, respectively.) Conclusion: Cisplatin has adverse effects on the uterus. Administration of recombinant Klotho was found to attenuate the cisplatin-induced damage but failed to preserve levels of the implantation molecules HOXA13 and alphaVbeta3. Further studies examining the effect of cisplatin toxicity using other implantation markers along with functional studies are needed