Naringin protects against paclitaxel-induced toxicity in rat testicular tissues by regulating genes in pro-inflammatory cytokines, oxidative stress, apoptosis, and JNK/MAPK signaling pathways.

Paclitaxel (PTX), which is actively used in the treatment of many types of cancer, has a toxic effect by causing increased oxidative stress in testicular tissues. Naringin (NRG) is a natural flavonoid found in plants, and its antioxidant properties are at the forefront. This study aims to investigate the protective feature of NRG in PTX-induced testicular toxicity. Thirty-five male Sprague rats were divided into five groups: control, NRG, PTX, PTX + NRG50, and PTX + NRG100. Rats were administered PTX (2 mg/kg, BW) intraperitoneally once daily for the first 5 days. Then, between the 6th and 14th days, NRG (50 and 100 mg/kg) was administered orally once a day. NRG reduced PTX-induced lipid peroxidation and increased testicular tissue antioxidant capacity (superoxide dismutase, catalase, glutathione peroxidase, and glutathione). While NRG reduces the mRNA expression levels of nuclear factor kappa B, tumor necrosis factor-alpha, interleukin-1 beta, cyclooxygenase-2, interleukin-6, inducible-nitric oxide synthase, mitogen-activated protein kinase 14 (MAPK)14, MAPK15, c-Jun N-terminal kinase, P53, Apaf1, Caspase3, Caspase6, Caspase9, and Bax in testicular tissues; it caused an increase in Nrf2, HO-1, NQO1 and Bcl-2 levels. NRG also improved the structural and functional integrity of testicular tissue disrupted by PTX. PTX-induced sperm damage was alleviated by NRG. NRG showed a protective effect by alleviating the PTX-induced testicular toxicity by increasing oxidative stress, inflammation, apoptosis, and autophagy.

Dietary composition influences sperm quality and testis damage via endoplasmic reticulum stress in lambs.

BACKGROUND: The metabolic impacts of including soya meal, wheat gluten and corn gluten in the diet of male lambs could influence their reproductive performance. OBJECTIVES: An experiment was carried out to assess the effects of corn gluten, wheat gluten and soya meal on the reproductive system of male lambs. METHODS: Twenty-four male Morkaraman lambs, aged 9 months, were utilized in this study and were fed experimental diets for 56 days. The lambs were divided into a control group (soybean meal + safflower meal), a corn group (corn gluten) and a wheat group (wheat gluten). RESULTS: The serum follicle-stimulating hormone level of the control group was significantly higher and tumour necrosis factor-alpha (TNF-α) level was lower than the wheat and corn gluten groups (p < 0.05). The lowest malondialdehyde level in testicular tissue was observed in the control group, whereas the highest was in the wheat gluten group (p < 0.05). The glutathione level in the control group was significantly higher than in the other groups (p < 0.05). The corn gluten group showed the highest CHOP and IRE1 levels; the lowest Bcl-2 levels and the highest IL-1B and P2 × 7R levels were found in the wheat group; and the lowest TNF-α levels were in the control group (p < 0.05). Additionally, the study revealed that diet had a significant impact on spermatological parameters of the testis such as diameter, volume and weight (p < 0.05). CONCLUSIONS: These results concluded that the inclusion of different protein sources in the diet of reproductive male lambs affects the metabolism of testicular tissue.

Effects of zingerone on rat induced testicular toxicity by sodium arsenite via oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, and autophagy pathways.

Objectives: This study aimed to investigate the effects of zingerone (ZNG) treatment on testicular toxicity in rats induced by sodium arsenite (SA). Materials and Methods: In the study, five groups were formed (n=7) and the experimental groups were designated as follows; Vehicle group, ZNG group, SA group, SA+ZNG 25 group, and SA+ZNG 50 group. While SA was administered orally to rats at 10 mg/kg/bw, ZNG was given to rats orally at 25 and 50 mg/kg/bw doses for 14 days. Results: As a result of the presented study, an increase was observed in the MDA contents of the testicular tissue of the rats administered SA, while significant decreases were observed in GSH levels, SOD, CAT, and GPx activities. The mRNA transcript levels of the pro-inflammatory genes NF-κB, TNF-α, IL-1ß, and IL-6 were triggered after SA administration. Additionally, SA administration caused inflammation by increasing RAGE, NLRP3, and JAK-2/STAT3 gene expression. Moreover, endoplasmic reticulum (ER) stress occurred in the testicular tissues of SA-treated rats and thus ATF-6, PERK, IRE1, and GRP78 genes were up-regulated. SA caused apoptosis by up-regulating Bax and Caspase-3 expressions and inhibiting Bcl-2 expression in testicles. SA caused histological irregularities in the testicles, resulting in decreased sperm quality. Conclusion: ZNG treatment reduced SA-induced oxidative stress, ER stress, inflammation, apoptosis, and histological irregularities in the testicles while increasing sperm quality. As a result, it was observed that ZNG could alleviate the toxicity caused by SA in the testicles.

Protective effects of naringin on colistin-induced damage in rat testicular tissue: Modulating the levels of Nrf-2/HO-1, AKT-2/FOXO1A, Bax/Bcl2/Caspase-3, and Beclin-1/LC3A/LC3B signaling pathways.

Antimicrobial agent resistance has become a growing health issue across the world. Colistin (COL) is one of the drugs used in the treatment of multidrug-resistant bacteria resulting in toxic effects. Naringin (NRG), a natural flavonoid, has come to the fore as its antioxidant, anti-inflammatory, and antiapoptotic activities. The aim of the present study was to determine whether NRG has protective effects on COL-induced toxicity in testicular tissue. Thirty-five male Spraque rats were randomly divided into five groups (n = 7 per group): Control, COL, NRG, COL + NRG 50, COL + NRG 100. COL (15 mg/kg b.w., i.p., once per/day), and NRG (50 or 100 mg/kg, oral, b.w./once per/day) were administered for 7 days. The parameters of oxidative stress, inflammation, apoptosis, and autophagic damage were evaluated by using biochemical, molecular, western blot, and histological methods in testicular issues. NRG treatment reversed the increased malondialdehyde level and reduced antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione) levels due to COL administration (p < 0.001), and oxidative stress damage was mitigated. Nuclear factor erythroid 2-related factor-2 pathway, one of the antioxidant defence systems, was stimulated by NRG (p < 0.001). NRG treatment reduced the levels of markers for the pathways of apoptotic (p < 0.001) and autophagic (p < 0.001) damages induced by COL. Sperm viability and the live/dead ratio were reduced by COL but enhanced by NRG treatment. Testicular tissue integrity was damaged by COL but showed a tendency to improve by NRG. In conclusion, COL exhibited toxic effect on testicular tissue by elevating the levels of oxidative stress, apoptosis, autophagy, inflammation, and tissue damage. NRG demonstrated a protective effect by alleviating toxic damage.

Silver Nanoparticles Loaded with Oleuropein Reduce Doxorubicin-Induced Testicular Damage by Regulating Endoplasmic Reticulum Stress, and Apoptosis.

Doxorubicin (DOX) is the most used chemotherapeutic agent for treating solid tumors. DOX treatment may lead to testicular damage using oxidative stress, resulting in infertility. These adverse effects may be prevented by the activation of antioxidant systems. Oleuropein (OLE) is a powerful flavonoid with several ameliorative effects, including antioxidative, antiproliferative, and anti-inflammatory. It would be more efficient and applicable in treating chronic human diseases if its poor bioavailability improves with a nano-delivery system. The current study aims to assess the histopathological changes and antioxidative effects of OLE loaded with silver nanoparticles oleuropein (OLE-AgNP) on the testicular injury triggered by DOX in rats. Forty-eight male albino rats were randomly divided into six groups as follows: the control, DOX (2.5 mg/kg), OLE (50 mg/kg), AgNP (100 mg/kg), OLE + AgNP (50 mg/kg), OLE (50 mg/kg) + DOX (2.5 mg/kg), AgNP (100 mg/kg) + DOX (2.5 mg/kg), and OLE-AgNP (50 mg/kg) + DOX (2.5 mg/kg) for 11 days. Oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress markers, sperm analysis, and histopathological analyses were performed on testicular tissues taken from rats decapitated after the applications and compared between the experimental groups. The tissue MDA level was lower in the OLE and OLE+AgNP-treated groups than in the DOX-treated group. In addition, SOD and GSH levels significantly increased in both the OLE and OLE+AgNP-treated groups compared to the DOX group. Both OLE and OLE+AgNP, particularly OLE+AgNP, ameliorated DOX-induced testicular tissue injury, as evidenced by reduced injury and improved seminiferous tubules and spermatocyte area. In addition, OLE and OLE+AgNP, especially OLE+AgNP, inhibited DOX-induced testicular tissue inflammation, apoptosis, and endoplasmic reticulum stress. The findings suggest that nanotechnology and the production of OLE+AgNP can ameliorate DOX-induced testicular damage.

Effect of syringic acid on oxidative stress, autophagy, apoptosis, inflammation pathways against testicular damage induced by lead acetate.

BACKGROUND: Heavy metals are one of the environmental pollutants. Lead (Pb) is one of the most common of these heavy metals. In this study, it was aimed at investigating the effects of syringic acid (SA) against testicular toxicity in rats administered lead acetate (PbAc). METHODS: In the present study, a total of 35 Sprague-Dawley rats, 7 in each group, were used. The rats were divided into 5 groups, with 7 male rats in each group. Rats were given PbAc and SA orally for 7 days. The effects of PbAc and SA on epididymal sperm quality and apoptosis, inflammation, oxidative stress and histopathological changes in testicular tissue were determined. RESULTS: While PbAc disrupted the seminiferous tubules and produced atrophic images, SA corrected these histological abnormalities. PbAc adminisration significantly reduced the levels of SOD, GSH, GPx, CAT, NRF-2 and NQO1 and significantly increased the levels of MDA and 8-OHdG in the testicular tissue of rats, while SA improved this situation. NF-κB, TNF-α, IL-1ß, NLRP3, RAGE, ATF6, PERK, IRE1, CHOP, and GRP78 genes expression levels increased with PbAc administration, however these levels decreased with SA administration. In addition, PbAc increased the levels of apoptotic markers Bax, Caspase-3 and APAF-1 and decreased the level of Bcl-2, while SA improved this situation. It was observed that PbAc significantly reduced sperm quality in rats, while SA positively affected sperm quality. CONCLUSION: As a result, SA administered against PbAc-induced testicular dysfunction in rats can provide effective protection at doses of 25 mg/kg/bw and 50 mg/kg/bw.

Effects of sinapic acid on lead acetate-induced oxidative stress, apoptosis and inflammation in testicular tissue.

In this study, the effect of lead acetate (PbAc) and sinapic acid (SNP) administration on oxidative stress, apoptosis, inflammation, sperm quality and histopathology in testicular tissue of rats was tried to be determined. PbAc was administered at a dose of 30 mg/kg/bw for 7 days to induce testicular toxicity in rats. Oral doses of 5 and 10 mg/kg/bw SNP were administered to rats for 7 days after PbAc administration. According to our findings, while PbAc administration increased MDA content in rats, it decreased GPx, SOD, CAT activity and GSH content. NF-kB, IL-1ß, TNF-α, and COX-2, which are among the inflammation parameters that increased due to PbAc, decreased with the administration of SNP. Nrf2, HO-1, and NQO1 mRNA transcript levels decreased with PbAc, but SNP treatments increased these mRNA levels in a dose-dependent manner. RAGE and NLRP3 gene expression were upregulated in PbAc treated rats. MAPK14, MAPK15, and JNK relative mRNA levels decreased with SNP treatment in PbAc treated rats. While the levels of apoptosis markers Bax, Caspase-3, and Apaf-1 increased in rats treated with PbAc, the level of Bcl-2 decreased, but SNP inhibited this apoptosis markers. PbAc caused histopathological deterioration in testis tissue and negatively affected spermatogenesis. When the sperm quality was examined, the decrease in sperm motility and spermatozoon density caused by PbAc, and the increase in the ratio of dead and abnormal spermatozoa were inhibited by SNP. As a result, while PbAc increased apoptosis and inflammation by inducing oxidative stress in testicles, SNP treatment inhibited these changes and increased sperm quality.

Effect of sulforaphane on long-term storage of rabbit semen.

In this study, it was aimed to determine the effect of sulforaphane (SFN) on rabbit semen cryopreservation. Semen collected from animals was divided into 5 equal volumes as Control, SFN 5 µM, SFN 10 µM, SFN 25 µM and SFN 50 µM groups. Afterwards, semen analyzes were performed. According to our results, there was no statistical difference between the groups at 4°C. However after freezing thawing, the highest total motility, progressive motility and rapid spermatozoa rate was seen in the 10 µM SFN group, while the lowest was observed in the 50 µM SFN group (P<0.05). Static sperm ratio was highest in the 50 µM group, while the lowest was observed in the 10 µM SFN group. When flow cytometry results examined the rate of acrosomal damaged and dead sperm was the lowest in the 10 µM SFN group, a statistical difference was observed between the control group (P<0.05). The highest rate of sperm with high mitochondrial membrane potential was seen in the 5 µM SFN and 10 µM SFN groups. Apoptosis and ROS rates were found to be lower in the experimental groups compared to the control groups (P<0.05). As a result, SFN supplementation at a dose of 10 µM increased the quality of sperm in the freezing and thawing processes of rabbit semen. In conclusion, 10 µM SFN improved the quality of cryopreservation of rabbit semen.

Carvacrol reduces abnormal and dead sperm counts by attenuating sodium arsenite-induced oxidative stress, inflammation, apoptosis, and autophagy in the testicular tissues of rats.

Arsenic (As) is a highly toxic metalloid. Carvacrol (CAR) is the active ingredient of Lamiaceae plants and has various biological and pharmacological properties. The present study investigated the protective effects of carvacrol (CAR) against testicular toxicity induced by sodium arsenite (SA). Rats were given SA (10 mg/kg) and/or CAR (25 or 50 mg/kg) for 14 days. Semen analyzes showed that CAR increased sperm motility and decreased the percentage of abnormal and dead sperm. It was determined that the oxidative stress induced by SA decreased with the increase of Nrf-2 and HO-1 expressions, SOD, CAT, GPx, and GSH levels, and MDA levels decreased after CAR treatment. It was observed that autophagy and inflammation triggered by SA in testicular tissue were alleviated by suppressing the expressions of LC3A, LC3B, MAPK-14, NF-κB, TNF-α, IL-1ß, iNOS, and COX-2 biomarkers in rats given CAR. Also, CAR treatment suppressed SA-induced apoptosis by inhibiting Bax and Caspase-3 expressions in testicles and up-regulating Bcl-2 expression. Histopathological analyzes showed that rats given SA had deterioration in tubule structure and spermatogenesis cell line, especially a serious loss of spermatogonia cells, atrophy of seminiferous tubules, and deterioration of germinal epithelium. In the group given CAR, the germinal epithelium and connective tissue were in normal morphological structure and an increase in seminiferous tubule diameters was observed. As a result, it was determined that oxidative stress, inflammation, autophagy, and apoptosis induced by SA were suppressed by CAR, thus protecting the testicular tissue from damage and increasing semen quality.

Effect of Hydrated Carbon 60 Fullerene on Frozen Ram Semen Quality.

The aim of this study was to evaluate the effect of hydrated carbon 60 fullerene (C60HyFn) on ram semen quality during cryopreservation. Three ejaculates from each of seven Akkaraman rams were collected using an artificial vagina during the nonbreeding season and pooled. Pooled semen samples were divided into 10 equal parts and diluted with tris + egg yolk extender not containing (control) and containing 100, 200, 400, and 800 nM and 1, 5, 10, 20, and 40 µM C60HyFn at 37°C. After addition of 5% glycerol and an equilibration process for 3 hours, the samples were frozen in 0.25-mL straws in an automatic freezing device at -140°C and stored in a liquid nitrogen container. Straws were thawed 24 hours after freezing and analyzed immediately with no incubation period. Motility, kinematic parameters, abnormality, vitality, hypo-osmotic swelling test (HOST), and oxidative stress levels were analyzed in thawed semen. Compared with the control, 200, 400, and 800 nM and 1 and 5 µM C60HyFn doses increased motility and HOST values and decreased the dead sperm rate. When compared with the control, addition of C60HyFn significantly decreased malondialdehyde levels (between 200 nM and 40 µM doses) and significantly increased glutathione peroxidase (between 800 nM and 40 µM doses) and catalase (between 1 and 40 µM doses) activities. In conclusion, results of this study show that the C60HyFn nanoparticles are nontoxic to ram semen and their supplementation in the extender is beneficial to sperm motility and membrane integrity after freeze-thawing.

Changes in heavy metal levels, reproductive characteristics, oxidative stress markers and testicular apoptosis in rams raised around thermal power plant.

Male reproductive dysfunction is one of the damages in the organism caused by heavy metals. In this study, it was aimed to investigate the changes in heavy metal levels in serum and testicular tissue, and serum hormone levels, epididymal spermatozoa characteristics, tissue oxidative stress levels, testicular histology and testicular apoptosis level in rams raised in remote and near regions of a thermal power plant. A total of 75 rams were divided into 3 groups according to the regions, where they were born and raised, being far [250 km distance, group 1 (control), n = 25], close (20 km distance, group 2, n = 25) and very close (10 km distance, group 3, n = 25) to the thermal power plant. The blood along with testis and epididymis tissues was taken from the animals after slaughtering. In addition, soil and water heavy metal analyzes were also performed. The highest levels of serum Al, Cr, As, Ag, Sn and testicular Al, V, Ni, Ag, Cd, Cr, As, Pb, and the lowest levels of serum Cu, testicular Cu and Zn were determined in group 3 compared to control. Soil and water heavy metal results were similar to those found in serum and testis. The lowest serum testosterone level, tissue glutathione-peroxidase and catalase activities, spermatozoon concentration, and the highest tissue malondialdehyde level, dead spermatozoon rate, Bax apoptotic protein expression level and Bax/Bcl-2 rate alongside some testicular histopathological lesions were found in group 3 in comparison to control. Significant correlations were determined between some heavy metal levels and some parameters measured. As a result, heavy metals accumulate in the soil and water in the region close to the thermal power plant. The endocrine and exocrine reproductive potentials of rams born and grown in these regions were clearly damaged by the increased testicular heavy metals due to water drank and herbs consumed.

Are the Early Postoperative Outcomes of Coronary Artery Bypass Grafting Surgery in Elderly Women Worse Compared to Men's?

OBJECTIVE:: To investigate the impact of gender difference in early postoperative outcomes in elderly patients (aged 70 or older) undergoing coronary artery bypass grafting surgery. METHODS:: Between October 2009 and December 2013, a total of 223 elderly patients (aged 70 or older) undergoing isolated primary coronary artery bypass grafting surgery were included in this retrospective observational cohort study. Patients were divided into two groups according to their gender. The patients' medical records were collected, their baseline preoperative characteristics, operative data, and postoperative outcomes were retrospectively reviewed, and the effect of gender difference in the early postoperative outcomes was analyzed. RESULTS:: Group 1 (female patients) and Group 2 (male patients) consisted of 71 and 152 patients, respectively. Mean age of patients was 74.4±3.6 years (range: 70-84 years). The level of EuroSCORE I, the incidence of hypertension and hyperlipidemia were significantly higher in Group 1, while the rate of smoking was significantly higher in Group 2. Mean postoperative intubation time, length of intensive care unit and hospital stay were longer in female patients than in male patients, but these differences were not statistically significant. No statistically significant difference between two groups in terms of the transfusion of blood products was observed. The rates of in-hospital mortality and major postoperative complications were statistically similar between the two groups. CONCLUSION:: In conclusion, the female gender was not associated with worse early postoperative outcomes in elderly patients undergoing coronary artery bypass grafting surgery.

Are the early postoperative outcomes of coronary artery bypass grafting surgery in elderly women worse compared to men's?

Abstract Objective: To investigate the impact of gender difference in early postoperative outcomes in elderly patients (aged 70 or older) undergoing coronary artery bypass grafting surgery. Methods: Between October 2009 and December 2013, a total of 223 elderly patients (aged 70 or older) undergoing isolated primary coronary artery bypass grafting surgery were included in this retrospective observational cohort study. Patients were divided into two groups according to their gender. The patients' medical records were collected, their baseline preoperative characteristics, operative data, and postoperative outcomes were retrospectively reviewed, and the effect of gender difference in the early postoperative outcomes was analyzed. Results: Group 1 (female patients) and Group 2 (male patients) consisted of 71 and 152 patients, respectively. Mean age of patients was 74.4±3.6 years (range: 70-84 years). The level of EuroSCORE I, the incidence of hypertension and hyperlipidemia were significantly higher in Group 1, while the rate of smoking was significantly higher in Group 2. Mean postoperative intubation time, length of intensive care unit and hospital stay were longer in female patients than in male patients, but these differences were not statistically significant. No statistically significant difference between two groups in terms of the transfusion of blood products was observed. The rates of in-hospital mortality and major postoperative complications were statistically similar between the two groups. Conclusion: In conclusion, the female gender was not associated with worse early postoperative outcomes in elderly patients undergoing coronary artery bypass grafting surgery.

Effect of Body Mass Index on Mortality and Morbidity in Patients Undergoing Coronary Artery Bypass Grafting Surgery.

BACKGROUND: This study aims to investigate the effect of body mass index (BMI) on mortality and morbidity in patients undergoing coronary artery bypass grafting (CABG) surgery. METHODS: We retrospectively evaluated the medical records of 403 patients undergoing coronary artery bypass surgery in our center. The patients were divided into 5 groups according to their BMI values. Preoperative demographic characteristics, operative data, and postoperative complications during the six-month follow-up period were compared between the groups. RESULTS: There were no statistically significant differences between the groups except the coexistence of peripheral artery disease (P = .009), ejection fraction (P = .021) and chronic obstructive pulmonary disease (P = .044). There were no statistically significant differences between the groups in terms of postoperative complications. No relationship was found between postoperative complications and the implemented surgical procedures. An overall 30-day mortality rate of 1.48% was observed, and the six-month mortality rate was 1.7%. CONCLUSION: According to this study, obesity does not lead to an increased risk of mortality and other adverse outcomes after CABG surgery. However, obesity may prolong hospital stay and increase the cost of CABG operation.

Early-Term Outcomes for Treatment of Saphenous Vein Insufficiency with N-Butyl Cyanoacrylate: A Novel, Non-Thermal, and Non-Tumescent Percutaneous Embolization Technique.

BACKGROUND: The purpose of this study was to present early-term outcomes of VariClose® Vein Sealing System, which is a novel, non-thermal, and non-tumescent percutaneous embolization technique for treatment of saphenous vein insufficiency. METHODS: Between March 2014 and July 2015, 189 saphenous veins in 141 patients were treated with Variclose Vein Sealing System containing n-butyl cyanoacrylate. Pre-, intra-, post-procedural, and follow-up data of patients were collected and retrospectively reviewed. RESULTS: Mean age of patients was 42.5 ± 14.0 years, of which 53% were female. Technical success rate of intervention was 98.9%. Mean procedure time was 14.3 ± 7.5 minutes. Eighty-nine percent of patients (n = 126/141) were available at mean follow-up time of 6.7 months. Mean Venous Clinical Severity Score was significantly improved from 8.3 ± 2.2 at pre-procedure period to 3.3 ± 1.8 at follow-up. No complete recanalization was observed, but 2 patients were presented with partial recanalization during follow-up. The complete occlusion rate was 98.4%. No serious adverse event related to procedure was observed. CONCLUSION: Variclose Vein Sealing System appears to be safe and effective in treatment of saphenous vein insufficiency. Further randomized studies with long-term outcomes are required for determining optimal treatment modality in patients with saphenous vein insufficiency.