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

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)

Losartan ve Lizinoprilin Sıçan Torasik Aort Kasılmaları Üzerindeki Etkilerinde Siklooksijenaz Enzimlerinin Rolü

Amaç: Siklooksijenaz (COX) enzimleri tarafından sentezlenen prostaglandinlerin anjiotensin dönüştürücü enzim (ADE) inhibisyonu ve anjiotensin AT1 reseptör antagonizmasının etkilerine katkıda bulunduğu ve ADE sinyal yolakları ile COX enzimleri arasında etkileşme olduğu ileri sürülmüştür. Bu çalışmada anjiotensin II (Ang II) reseptör antagonisti bir ilaç olan losartan veya ADE inhibitörü bir ilaç olan lizinoprilin izole organ banyosunda sıçan torasik aorta kasılmaları üzerindeki etkilerinde COX enzimlerinin rolünün araştırılmasını amaçladık. Gereç ve Yöntem: Losartan (10-6,10-5,10-4M), lizinopril (10-6,10-5,10-4M) ve selektif olmayan bir COX inhibitörü olan dipironun (10-4,7x10-4,2x10-3M) tek başına fenilefrin (Phe) (10-7M), potasyum klorür (KCl) (6x10-2M) ve Ang II (10-8M) ile indüklenen kasılmalar üzerindeki ve ayrıca losartan veya lizinoprilin dipironla kombinasyonlarının Phe veya KCl ile indüklenen kasılmalar üzerindeki yanıtları kaydedildi. Bulgular: Tek başlarına verildiklerinde dipiron ve losartan Phe, KCl ve Ang II ile indüklenen kasılmaları baskılarken, lizinopril sadece Phe ve Ang II ile indüklenen kasılmaları baskıladı. COX enzimlerinin inhibisyonu (dipiron 10-4,7x10-4,2x10-3M tarafından sırasıyla COX-3, COX-3+-1, COX1+-2+3), losartan veya lizinoprilin gevşetici etkilerini artırdı. Ayrıca dipiron, lizinoprilin KCl ile indüklenen kasılmalar üzerindeki etkisini potansiyalize etti. Sonuç: Dipironun losartan veya lizinoprilin düz kas gevşetici etkilerini artırdığını ve COX enzim inhibisyonunun bu gevşemede rolü olabileceğini ileri sürüyoruzObjective: It was suggested that prostaglandins which are synthesized by cyclooxygenase (COX) enzymes contribute to the actions of angiotensin-converting enzyme (ACE) inhibition and angiotensin AT1 receptor antagonism and there is an interaction between ACE signaling pathway and COX enzymes. We aim to investigate the role of COX enzymes in the effects of losartan, an angiotensin II (Ang II) receptor antagonist or lisinopril, an ACE inhibitor, on the contractions of rat thoracic aorta in isolated tissue bath. Materials and Methods: Responses of losartan (10-6, 10-5, 10-4 M), lisinopril (10-6, 10-5, 10-4 M), and non-selective COX inhibitor dipyrone (10-4, 7 × 10-4, 2 × 10-3 M) alone to the contractions induced by phenylephrine (Phe) (10-7 M), potassium chloride (KCl) (6 × 10-2 M), Ang II (10-8 M) and responses of losartan or lisinopril in combination with dipyrone to the contractions induced by Phe or KCl were recorded. Results: When used alone, dipyrone and losartan inhibited Phe, KCl, and Ang II-induced contractions, whereas lisinopril inhibited only Phe and Ang II-induced contractions. Inhibition of COX enzymes (COX-3, COX-3 + COX-1, COX-1+ COX-2 + COX-3 by dipyrone 10-4, 7 × 10-4, 2 × 10-3 M, respectively) augmented the relaxant effects of losartan or lisinopril. Also, dipyrone potentiated the effect of lisinopril on KCl-induced contractions. Conclusion: We suggest that dipyrone increases the smooth-muscle relaxing effects of losartan or lisinopril and that COX enzyme inhibition may have a role in the enhancement of this relaxatio

The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta

WOS: 000399175500004PubMed ID: 28416926Objective: It was suggested that prostaglandins which are synthesized by cyclooxygenase (COX) enzymes contribute to the actions of angiotensin-converting enzyme (ACE) inhibition and angiotensin AT1 receptor antagonism and there is an interaction between ACE signaling pathway and COX enzymes. We aim to investigate the role of COX enzymes in the effects of losartan, an angiotensin II (Ang II) receptor antagonist or lisinopril, an ACE inhibitor, on the contractions of rat thoracic aorta in isolated tissue bath. Materials and Methods: Responses of losartan (10(-6), 10(-5), 10(-4) M), lisinopril (10(-6), 10(-5), 10(-4) M), and non-selective COX inhibitor dipyrone (10(-4), 7 x 10(-4), 2 x 10(-3) M) alone to the contractions induced by phenylephrine (Phe) (10(-7) M), potassium chloride (KCl) (6 x 10(-2) M), Ang II (10(-8) M) and responses of losartan or lisinopril in combination with dipyrone to the contractions induced by Phe or KCl were recorded. Results: When used alone, dipyrone and losartan inhibited Phe, KCl, and Ang II-induced contractions, whereas lisinopril inhibited only Phe and Ang II-induced contractions. Inhibition of COX enzymes (COX-3, COX-3 + COX-1, COX-1+ COX-2 + COX-3 by dipyrone 10(-4), 7 x 10(-4), 2 x 10(-3) M, respectively) augmented the relaxant effects of losartan or lisinopril. Also, dipyrone potentiated the effect of lisinopril on KCl-induced contractions. Conclusion: We suggest that dipyrone increases the smooth-muscle relaxing effects of losartan or lisinopril and that COX enzyme inhibition may have a role in the enhancement of this relaxation

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

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

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

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

Prevention of Burn Wound Progression by Mesenchymal Stem Cell Transplantation: Deeper Insights Into Underlying Mechanisms

Introduction Burns are dynamic wounds that may present a progressive expansion of necrosis into the initially viable zone of stasis. Therefore, salvage of this zone is a major subject of focus in burn research. The beneficial effects of mesenchymal stem cells (MSCs) on the survival of the zone of stasis have been previously documented. However, many gaps still exist in our knowledge regarding the underlying protective mechanisms. Hence, this study was designed to evaluate the pathophysiological basis of MSCs in the prevention of burn wound progression