Intracerebroventricular PROK2 infusion could increase the secretion of male reproductive hormones by stimulating the HPG axis.

BACKGROUND: Prokineticin 2 (PROK2), an important neuropeptide that plays a key role in the neuronal migration of gonadotropin-releasing hormone (GnRH) in the hypothalamus, is known to have regulatory effects on the gonads. In the present study, the impact of intracerebroventricular (icv) PROK2 infusion on hypothalamic-pituitary-gonadal axis (HPG) hormones, testicular tissues, and sperm concentration was investigated. METHODS AND RESULTS: Rats were randomly divided into four groups: control, sham, PROK2 1.5 and PROK2 4.5. Rats in the PROK2 1.5 and PROK2 4.5 groups were administered 1.5 nmol and 4.5 nmol PROK2 intracerebroventricularly for 7 days via an osmotic mini pump (1 µl/h), respectively. Rat blood serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone hormone levels were determined with the ELISA method in the blood samples after 7 days of infusion. GnRH mRNA expression was determined with the RT-PCR in hypothalamus tissues. analyze Sperm concentration was determined, and testicular tissue was examined histologically with the hematoxylin-eosin staining method. It was observed that GnRH mRNA expression increased in both PROK2 infusion groups. Serum FSH, LH and testosterone hormone levels also increased in these groups. Although sperm concentration increased in PROK2 infusion groups when compared to the control and sham, the differences were not statistically significant. Testicular tissue seminiferous epithelial thickness was higher in the PROK2 groups when compared to the control and sham groups. CONCLUSION: The present study findings demonstrated that icv PROK2 infusion induced the HPG axis. It could be suggested that PROK2 could be a potential agent in the treatment of male infertility induced by endocrinological defects.

Protective effect of astaxanthin on testis torsion/detorsion injury through modulation of autophagy.

A significant clinical condition known as testicular torsion leads to permanent ischemic damage to the testicular tissue and consequent loss of function in the testicles. In this study, it was aimed to evaluate the protective effects of Astaxanthin (ASTX) on testicular damage in rats with testicular torsion/detorsion in the light of biochemical and histopathological data. Spraque Dawley rats of 21 were randomly divided into three groups; sham, testicular torsion/detorsion (TTD) and astaxanthin + testicular torsion/detorsion (ASTX + TTD). TTD and ASTX + TTD groups underwent testicular torsion for 2 hours and then detorsion for 4 hours. Rats in the ASTX + TTD group were given 1 mg/kg/day astaxanthin by oral gavage for 7 days before torsion. Following the detorsion process, oxidative stress parameters and histopathological changes in testicular tissue were evaluated. Malondialdehyde (MDA) and total oxidant status (TOS) levels were significantly decreased in the ASTX group compared to the TTD group, while superoxide dismutase (SOD), glutathione (GSH) and total antioxidant status (TAS) levels were increased (p < 0.05). Moreover, histopathological changes were significantly reduced in the group given ASTX (p < 0.0001). It was determined that ASTX administration increased Beclin-1 immunoreactivity in ischemic testicular tissue, while decreasing caspase-3 immunoreactivity (p < 0.0001). Our study is the first to investigate the antiautophagic and antiapoptotic properties of astaxanthin after testicular torsion/detorsion based on the close relationship of Beclin-1 and caspase-3 in ischemic tissues. Our results clearly demonstrate the protective effects of ASTX against ischemic damage in testicular tissue. In ischemic testicular tissue, ASTX contributes to the survival of cells by inducing autophagy and inhibiting the apoptosis.

Enhancement of enzyme activity by laser-induced energy propulsion of upconverting nanoparticles under near-infrared light: A comprehensive methodology for in vitro and in vivo applications.

If the appropriate immobilization method and carrier support are not selected, partial decreases in the activity of enzymes may occur after immobilization. Herein, to overcome this challenge, an excitation mechanism that enables energy transfer was proposed. Modified upconverting nanoparticles (UCNPs) were constructed and the important role of near-infrared (NIR) excitation in enhancing the catalytic activity of the enzyme was demonstrated. For this purpose, UCNPs were first synthesized via the hydrothermal method, functionalized with isocyanate groups, and then, PEG-L-ASNase was immobilized via covalent binding. UCNPs with and without PEG-L-ASNase were extensively characterized by different methods. These supports had immobilization yield and activity efficiency of >96 % and 78 %, respectively. Moreover, immobilized enzymes exhibited improved pH, thermal, and storage stability. In addition, they retained >65 % of their initial activity even after 20 catalytic cycles. Biochemical and histological findings did not indicate a trend of toxicity in rats due to UCNPs. Most importantly, PEG-L-ASNase activity was triggered approximately 5- and 2-fold under in vitro and in vivo conditions, respectively. Overall, it is anticipated that this pioneering work will shed new light on the realistic and promising usage of NIR-excited UCNPs for the immobilization of enzymes in expensive and extensive applications.

Does apocynin increase liver regeneration in the partial hepatectomy model?

BACKGROUND: Hepayocyte loss may develop secondary to liver surgery and at this point liver regeneration plays a significant act in terms of liver reserve. The purpose of this research was to investigate the efficacy of apocynin on liver regeneration and preservation after partial hepatectomy in rats. METHODS: A total of 32 rats, have been divided into 4 groups (n: 8) for hepatectomy model. Inflammatory and antiinflammatory parameters were measured from blood and liver tissue samples. In addition, the effects of apocynin were examined immunohistochemically and histopathologically from liver tissue. RESULTS: In liver tissue samples, a significant difference has been found in glutathione peroxidase, total nitrite, catalase, oxidative stress index, total antioxidant and total oxidant status between sham and hepatectomy groups. A significant difference has been achieved between hepatectomy and posthepatectomy-Apocynin in terms of glutathione peroxidase and oxidative stress index. Total antioxidant status, oxidative stress index, and total oxidant status were significantly different only between the sham and the hepatectomy groups. Statistical differences were found between sham and hepatectomy groups and between hepatectomy and pre+post-hepatectomy-Apocynin groups in terms of serum glutathione, malondialdehyde, total nitrite, and L-Arginine. There were significant differences between the sham and hepatectomy groups, between hepatectomy and posthepatectomy-apocynin groups, between posthepatctomy-apocynin and pre+posthepatectomy-apocynin groups in terms of sinusoidal dilatation, intracytoplasmic vacuolization and glycogen loss (p < 0.001), in all histopathologic parameters except sinusoidal dilatation (p < 0.05). However, significant Ki-67 increases have been elaborated in hepatectomy, posthepatectomy-apocynin, and pre+posthepatectomy-apocynin groups compared to sham group (p < 0.001), in pre+posthepatectomy apocynin group compared to hepatectomy and posthepatectomy-apocynin groups (p < 0.001). DISCUSSION: Histopathology, immunohistochemistry, and biochemistry results of this study revealed that apocynin has a protective effect on enhancing liver regeneration in partial hepatectomy cases in rats.

Comparison of 'primary repair' and 'placing a drain without repair' methods in duodenum perforations.

BACKGROUND: Duodenal ulcer perforation is a serious condition. A number of methods have been defined and used in surgical treatment. In this study, it was aimed to compare the effectiveness of 'primary repair' and 'drain placement without repair' methods in duodenal perforations using an animal model. METHODS: Three equivalent groups of ten rats each were formed. Perforation was created in the duodenum in the first (primary repair/sutured group) and the second group (drain placement without repair/sutureless drainage group). In the first group, the per-foration was repaired with sutures. In the second group, only a drain was placed in the abdomen without sutures. In the third group (control group), only laparotomy was performed. Neutrophil count, sedimentation, serum C-reactive protein (CRP), serum total an-tioxidant capacity (TAC), serum total thiol, serum native thiol, and serum myeloperoxidase (MPO) analyses were performed on animal subjects in the pre-operative period and on the post-operative 1st and 7th days. Histological and immunohistochemical (transforming growth factor-beta 1 [TGF-ß1]) analyzes were performed. Blood analysis, histological, and immunohistochemical findings obtained from the groups were compared statistically. RESULTS: There was no significant difference between the first and second groups, except for the TAC on the post-operative 7th day and MPO values on the post-operative 1st day (P>0.05). Although tissue healing was more pronounced in the second group than in the first group, there was no significant difference between the groups (P>0.05). TGF-ß1 immunoreactivity observed in the second group was found to be significantly higher than in the first group (P<0.05). CONCLUSION: We think that the sutureless drainage method is as effective as the primary repair method in the treatment of duo-denal ulcer perforation and can be safely applied as an alternative to the primary repair method. However, further studies are needed to fully determine the efficacy of the sutureless drainage method.

Modeling Based on Ensemble Learning Methods for Detection of Diagnostic Biomarkers from LncRNA Data in Rats Treated with Cis-Platinum-Induced Hepatotoxicity.

BACKGROUND: The first aim of this study is to perform bioinformatic analysis of lncRNAs obtained from liver tissue samples from rats treated with cisplatin hepatotoxicity and without pathology. Another aim is to identify possible biomarkers for the diagnosis/early diagnosis of hepatotoxicity by modeling the data obtained from bioinformatics analysis with ensemble learning methods. METHODS: In the study, 20 female Sprague-Dawley rats were divided into a control group and a hepatotoxicity group. Liver samples were taken from rats, and transcriptomic and histopathological analyses were performed. The dataset achieved from the transcriptomic analysis was modeled with ensemble learning methods (stacking, bagging, and boosting). Modeling results were evaluated with accuracy (Acc), balanced accuracy (B-Acc), sensitivity (Se), specificity (Sp), positive predictive value (Ppv), negative predictive value (Npv), and F1 score performance metrics. As a result of the modeling, lncRNAs that could be biomarkers were evaluated with variable importance values. RESULTS: According to histopathological and immunohistochemical analyses, a significant increase was observed in the sinusoidal dilatation and Hsp60 immunoreactivity values in the hepatotoxicity group compared to the control group (p < 0.0001). According to the results of the bioinformatics analysis, 589 lncRNAs showed different expressions in the groups. The stacking model had the best classification performance among the applied ensemble learning models. The Acc, B-Acc, Se, Sp, Ppv, Npv, and F1-score values obtained from this model were 90%, 90%, 80%, 100%, 100%, 83.3%, and 88.9%, respectively. lncRNAs with id rna-XR_005492522.1, rna-XR_005492536.1, and rna-XR_005505831.1 with the highest three values according to the variable importance obtained as a result of stacking modeling can be used as predictive biomarker candidates for hepatotoxicity. CONCLUSIONS: Among the ensemble algorithms, the stacking technique yielded higher performance results as compared to the bagging and boosting methods on the transcriptomic data. More comprehensive studies can support the possible biomarkers determined due to the research and the decisive results for the diagnosis of drug-induced hepatotoxicity.

Effects of the apricot diets containing sulfur dioxide at different concentrations on rat testicles.

Due to its antioxidant and antimicrobial properties, sulfur dioxide (SO2) is widely used in foods and beverages to prevent the growth of microorganisms and to preserve the color and flavor of fruits. However, the amount of SO2 used in fruit preservation should be limited due to its possible adverse effects on human health. The present study was designed to investigate the effects of different SO2 concentrations in apricot diets on rat testes. Animals were randomly divided into six groups. The control group was fed a standard diet, and the other groups were fed apricot diet pellets prepared with (w/w) 10% dried apricots containing SO2 at different concentrations (1500 ppm, 2000 ppm, 2500 ppm, 3000 ppm, and 3500 ppm/kg) for 24 weeks. After sacrification, testicles were evaluated biochemically, histopathologically, and immunohistopathologically. Our results showed that an apricot diet containing 1500 ppm and 2000 ppm SO2 did not cause significant changes in testis. However, it was determined that tissue testosterone levels decreased as the amount of SO2 (2500 ppm and above) increased. Apricot diet containing 3500 ppm SO2 caused a significant increase in spermatogenic cell apoptosis, oxidative damage, and histopathological changes. In addition, a decrease in the expression of connexin-43, vimentin, and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) was observed in the same group. In summary, the results show that sulfurization of apricot at high concentrations such as 3500 ppm may lead to male fertility problems in the long term through mechanisms such as oxidative stress, spermatogenic cell apoptosis, and inhibition of steroidogenesis.

The effects of pentoxifylline and caffeic acid phenethyl ester on TNF-α and lung histopathology in D-galactosamine-induced pulmonary injury in rats.

In this study, we aimed to investigate the effects of pentoxifylline [PTX] and caffeic acid phenethyl ester [CAPE] in D-galactosamine [D-GAL]-induced pulmonary injury in rats. The rats were randomly divided into six groups: control, D-GAL, D-GAL+PTX, D-GAL+CAPE, PTX and CAPE. Each group included eight animals. Lung sections from the control, PTX and CAPE groups had a normal histological appearance. The D-GAL group showed histopathological changes in lung tissue, including haemorrhage, oedema, inter-alveolar septal thickening and widespread infiltration of inflammatory lymphocytes and macrophages. Administration of PTX and CAPE significantly reduced histopathological damage scores in the D-GAL+PTX and D-GAL+CAPE groups compared with the D-GAL group. PTX and CAPE treatment also significantly decreased malondialdehyde levels, increased levels of reduced GSH and increased catalase and superoxide dismutase activity in lung tissue samples. These results indicate that the destructive effects of D-GAL-induced inflammation in the rat lung are significantly reduced following administration of PTX and CAPE.

Angiotensin II type 2 receptor agonist treatment of doxorubicin induced heart failure.

Doxorubicin (DOX) is an anthracycline derivative used for treatment of malignancies; however, its clinical use is limited by its cardiotoxicity. We investigated the effects of angiotensin II type 2 receptor agonist compound 21 (C21) on DOX induced heart failure in rat heart. We compared C21 with losartan (LOS), an AT 1 receptor antagonist used for treating heart failure. We allocated 40 rats into five groups of eight: saline treated control group, DOX group administered a single 20 mg/kg dose of DOX, DOX + C21 group administered 0.3 mg/kg C21 for 21 days following the 20 mg/kg dose of DOX, DOX + losartan (LOS) group administered a 21 day regimen of 20 mg/kg LOS following the single dose of DOX, and a DOX + LOS + C21 group administered 0.3 mg/kg C21 and 20 mg/kg LOS for 21 days following the single dose of DOX. We assessed histopathology and conducted echocardiograpic and hemodynamic measurements. Left ventricular ejection fraction (EF) was reduced only in the DOX treated group. C21, LOS and C21 + LOS therapy prevented decreased EF due to DOX. Less histopathology was observed in the DOX + LOS + C21 group than for the other treatment groups. Application of C21 decreased DOX induced cardiac injury similar to LOS. Combined use of C21 and LOS was most beneficial for DOX induced heart failure.

Protective effect of dexpanthenol against methotrexate-induced liver oxidative toxicity in rats.

Methotrexate is a familiar chemotherapeutic preferred in a wide range of clinical fields such as leukemia, psoriasis, rheumatoid arthritis, neoplastic and autoimmune disorders. However, methotrexate therapy has limitations as it causes severe side effects from which liver damage is the most important one. Several antioxidant compounds have been studied against methotrexate related liver toxicity, but dexpanthenol has not been experienced. Vitamin B5-derived dexpanthenol is a usual therapeutic having a potent anti-inflammatory and antioxidant effect. In this study, we aimed to evaluate the ameliorating effect of dexpanthenol against methotrexate-induced hepatotoxicity. We performed our experiments on Wistar albino rats divided randomly into four groups involving control, dexphantenol, dexpanthenol + methotrexate and methotrexate applied animals. After this experimental work on rats, for the first time, we showed dexpanthenol improvement effect on ROS-caused hepatotoxicity initiated by methotrexate administration in terms of liver tissue antioxidant/oxidant enzymes, liver function tests, and histological changes. We suggest that dexpanthenol might be applied during methotrexate treatment in order to reduce the liver toxicity. However, further studies are needed to find out the optimal dose regimen and to understand the mechanism of action.

Effects of apocynin on sciatic nerve injury in rabbits.

We investigated the effects of apocynin (APO) on experimental sciatic nerve compression injury in rabbits. We used 21 male rabbits divided randomly into three groups of seven. The control group was subjected to sciatic nerve compression with no further intervention. The APO treated group was subjected to compression injury and 20 mg/kg APO was administered daily for 21 days by intraperitoneal injection beginning the day after the injury. The sham group was treated with APO without injury. The control group exhibited shrinkage of axons, disruption of myelin sheaths and loss of nerve fibers. The damage for the control group was significantly greater than for the sham group. The severity of histopathology was decreased in the APO treated group compared to the control group, as was the oxidative stress index. Our findings suggest that APO treatment may contribute to healing of sciatic nerve damage.

Activation of the Mas receptors by AVE0991 and MrgD receptor using alamandine to limit the deleterious effects of Ang II-induced hypertension.

The MrgD receptor agonist, alamandine (ALA) and Mas receptor agonist, AVE0991 have recently been identified as protective components of the renin-angiotensin system. We evaluated the effects of ALA and AVE0991 on cardiovascular function and remodeling in angiotensin (Ang) II-induced hypertension in rats. Sprague Dawley rats were subject to 4-week subcutaneous infusions of Ang II (80 ng/kg/min) or saline after which they were treated with ALA (50 µg/kg), AVE0991 (576 µg/kg), or ALA+AVE0991 during the last 2 weeks. Systolic blood pressure (SBP) and heart rate (HR) values were recorded with tail-cuff plethysmography at 1, 15, and 29 days post-treatment. After euthanization, the heart and thoracic aorta were removed for further analysis and vascular responses. SBP significantly increased in the Ang II group when compared to the control group. Furthermore, Ang II also caused an increase in cardiac and aortic cyclophilin-A (CYP-A), monocyte chemoattractant protein-1 (MCP-1), and cardiomyocyte degeneration but produced a decrease in vascular relaxation. HR, matrix metalloproteinase-2 and -9, NADPH oxidase-4, and lysyl oxidase levels were comparable among groups. ALA, AVE0991, and the drug combination produced antihypertensive effects and alleviated vascular responses. The inflammatory and oxidative stress related to cardiac MCP-1 and CYP-A levels decreased in the Ang II+ALA+AVE0991 group. Vascular but not cardiac angiotensin-converting enzyme-2 levels decreased with Ang II administration but were similar to the Ang II+ALA+AVE0991 group. Our experimental data showed the combination of ALA and AVE0991 was found beneficial in Ang II-induced hypertension in rats by reducing SBP, oxidative stress, inflammation, and improving vascular responses.

Protective effects of dexpanthenol in carbon tetrachloride-induced myocardial toxicity in rats.

Exposure to various organic compounds including several environmental pollutants and drugs can cause cellular damage through the generation of lipid peroxidation products. Carbon tetrachloride (CCl4) is a potent toxic agent that causes peroxidative degeneration in many tissues. Dexpanthenol (Dxp) is a member of the B complex vitamins that exhibits antioxidant effects against lipid peroxidation products. This study was designed to evaluate the cardioprotective effect of Dxp against CCl4-induced myocardial toxicity in rats. Administration of a single dose of CCl4 caused cardiotoxicity by the increase in lipid peroxidation and histopathological changes (cardiomyocytes degeneration, interstitial edema) in the myocardial tissue. Moreover, CCl4 caused a decrease in lactate dehydrogenase (LDH) and troponin-I immunoreactivities, while significantly increasing tumor necrosis factor-alpha (TNF-α) and caspase-3 immunoreactivities. On the other hand, administration of Dxp improved biochemical, histopathological, and immunohistochemical parameters compared to the CCl4 treated group. Overall, this study suggests that Dxp is effective in inhibiting CCl4-induced lipid peroxidation, and that administration of Dxp may help prevent CCl4 related inflammation, necrosis, and apoptosis on the cardiac tissue.

Effects of taurine and apocynin on the zone of stasis.

BACKGROUND: Among the zones of coagulation, hyperemia and stasis that occur in the burned area, the most intense metabolic process and the highest sensitivity to recovery with treatment is the zone of stasis.This metabolic process is related to how well the tissues in the zone of stasis can cope with oxidative stress. If the tissues in the zone of stasis are saved, the burn area will potentially heal faster and with less scar. In this study, we examined the effects of taurine amino acids and apocynin molecules on saving the tissues in the burn zone of stasis. METHODS: The study was conducted with 48 rats. The burn zone of stasis was created according to the pattern previously described in the literature as comb burn model. In the 21-day study, biopsies were taken for histological examination on the 3rd, 7th and 21st days of the study. In addition, macroscopic photographic analysis was performed. Biopsies were taken for biochemical analysis on the 21st day. Histologically, inflammation, reepithelialization, and collagenization were evaluated, and the CD34 immunoreactivity was analysed. Biochemically, CAT, SOD, tGSH, TAS, TOS, MDA and PPC values were determined. RESULTS: In the histological examination, on the 3rd, 7th and 21st days, inflammation was found to be reduced in the groups given taurine and apocynin on the 3rd day. On the 7th day, better reepithelialization and collagenization were observed in the group given taurine. Significant reepithelialization, collagenization and hair follicle development were observed in the groups given taurine and apocynin on the 21st day. In the biochemical analysis, the effects of apocynin on antioxidant enzymes were determined to be prominent. While we found no significant difference on the 3rd and 7th days in the photographic analysis, taurine and apocynin were observed to act synergistically on the 21st day and significantly reduced the burned areas. CONCLUSION: On the 3rd day, taurine and apocynin prevented inflammation, the effects of taurine in the zone of stasis in the early period (7th day) are more pronounced, the effect of apocynin on antioxidant enzymes is more pronounced. In the late period (21st day), taurine and apocynin were found to be more effective in saving the zone of stasis by creating a synergistic effect.

Effects of Low- and High-Dose Valproic Acid and Lamotrigine on the Heart in Female Rats.

Epilepsy is a chronic neurological disease that affects more than 50 million people worldwide. Antiepileptic drugs (AEDs) are the mainstay of treatment for most patients with epilepsy. However, AEDs have been reported to be associated with adverse cardiac effects. In this study, it was aimed to investigate the possible cardiac effects of low-dose (LD) and high-dose (HD) treatment of valproic acid (VPA) and lamotrigine (LTG), which are commonly used AEDs, in rats without epilepsy. Rats were randomly grouped as control, LD-VPA, HD-VPA, LD-LTG, and HD-LTG. The cardiac effects of AEDs were evaluated using immunohistological, biochemical, and hemodynamic parameters. A dose-dependent increase in the intensity of caspase-3 staining was detected in the VPA and LTG groups. The intensity of connexin-43 and troponin-T staining in the VPA groups and desmin staining in the LTG groups was significantly reduced. Biochemically, HD-VPA and HD-LTG administrations caused a significant increase in MDA level in myocardial tissue. In addition, as a result of hemodynamic evaluations, cardiac functions were found to be affected and blood pressure increased in HD-LTG group. The results of present study support that VPA and LTG treatment can increase cardiac risk markers.

Dose-dependent subacute cardiovascular effects of modafinil in rats.

Modafinil is used for the treatment of various sleep disorders; however, its usage among healthy individuals is also increasing. There are a limited number of cardiovascular side effects, including ischemic T-wave changes, dyspnea, hypertension, and tachycardia in the literature. Our research aimed to investigate the dose-dependent subacute cardiovascular effects of modafinil in rats. Thirty-two rats were randomly and equally assigned to a control group (vehicle-treated for 14 days), a subacute low-dose group (SALD, 10 mg/kg for 14 days), a subacute moderate-dose group (SAMD, 100 mg/kg for 14 days), and a subacute high-dose group (SHD, 600 mg/kg for 14 days). The cardiovascular effects of modafinil were evaluated using hemodynamic, biochemical, electrocardiographic, electrophysiologic, and histopathologic parameters. In terms of hemodynamic parameters, heart rate, and systolic/diastolic/mean blood pressure levels, electrophysiological parameters did not reach statistical significance among the groups (p > 0.05). The incidence of T-wave negativity in SAMD and SAHD groups was 25 and 37.5%, respectively. Moreover, one rat per group was affected by an atrioventricular blockage. Malondialdehyde, superoxide dismutase, catalase, and reduced glutathione levels in the heart and vascular tissues, serum troponin-I, and creatine kinase levels were similar between the modafinil-administered groups and the control group (p > 0.05); this indicates that modafinil activated neither oxidative stress nor antioxidant pathway. Also, there was no difference in histopathological parameters between groups (p > 0.05). Supratherapeutic doses of modafinil may have the potential to cause ischemic cardiac damage and atrioventricular blockage, despite inconsistency with literature findings; however, this does not pertain to hemodynamic changes.

Effects of antiepileptic drugs on ovaries of female Wistar rats.

Valproate (VPA) induced changes in ovarian morphology are observed in humans with epilepsy and in non-epileptic animals. The effects of lamotrigine (LTG) on female reproduction is not well known. We investigated whether LTG might be a safer drug for use with patients of reproductive age. Forty Wistar albino female rats were divided into five groups. The control group was injected with saline-vehicle solution. The low dose (LD)-VPA group was injected with 100 mg/kg VPA. The high dose (HD)-VPA group was injected with 500 mg/kg VPA. The LD-LTG group was injected with 10 mg/kg LTG. The HD-LTG group was injected with 50 mg/kg LTG. We evaluated histological and biochemical changes in the ovaries. The number of atretic and cystic follicles was increased in the HD-VPA and HD-LTG groups compared to the control group. A significant increase in malondialdehyde level was found in the VPA groups compared to the control and LTG groups. No significant differences in total glutathione levels or superoxide dismutase activity were found among study groups. Catalase activity was significantly higher in HD-VPA and HD-LTG groups compared to the control, LD-VPA and LD-LTG groups. Prevalence and intensity of caspase-3 immunoreactivity in the luteal cells were significantly greater in the HD-LTG group compared to the control group. VPA administration caused polycystic ovarian syndrome-like changes in the ovary. We found that LD-LTG, which reflects the dose for humans, might be a safer option for use during the reproductive age.

Photocrosslinkable gelatin/collagen based bioinspired polyurethane-acrylate bone adhesives with biocompatibility and biodegradability.

Hard or soft tissue adhesives have been presented as a promising candidate to replace traditional wound closure methods. However, there are mechanical strength problems in biological adhesives and biocompatibility problems in synthetic-based adhesives. At this point, we aimed to remove all these disadvantages and produce a single adhesive that contains all the necessary features and acrylate functionalized UV-curable polyurethane formulations were produced with high crosslink density, high adhesion strength, biocompatibility and injectable property for easy application as potential biomedical adhesives. Aliphatic isophorone diisocyanate (IPDI) was used as the isocyanate source and ß-cyclodextrin was used for host-guest relationship with gentamicin by crosslinking. Proteins (gelatin (GEL), collagen (COL)) and PEGs of various molecular weight ranges (P200, P400, P600) were selected as the polyol backbone for polyurethane synthesis due to their multiple biological activities such as biocompatibility, biodegradability, biomimetic property. Several techniques have been used to characterize the structural, thermal, morphological, and various other physicochemical properties of the adhesive formulations. Besides, the possibility of its use as a hard tissue adhesive was investigated by evaluating the tissue adhesion strength in vitro and ex vivo via a universal testing analyzer in tensile mode. Corresponding adhesive formulations were evaluated by in vitro and in vivo techniques for biocompatibility. The best adhesion strength results were obtained as 3821.0 ±â€¯214.9, and 3722.2 ±â€¯486.8 kPa, for IPDI-COL-P200 and IPDI-GEL-P200, respectively. Good antibacterial activity capability toward Escherichia coli Pseudomonas aeruginosa, and Staphylococcus aureus were confirmed using disc diffusion method. Moreover, cell viability assay demonstrated that the formulations have no significant cytotoxicity on the L929 fibroblast cells. Most importantly, we finally performed the in vivo biodegradability and in vivo biocompatibility evaluations of the adhesive formulations on rat model. Considering their excellent cell/tissue viability, fast curable, strong adhesion, high antibacterial character, and injectability, these adhesive formulations have significant potential for tissue engineering applications.

Protective effects of naringin on valproic acid-induced hepatotoxicity in rats.

Valproic acid (VPA) is mainly prescribed to treat epilepsy. VPA has been reported to be associated with many adverse effects, including hepatotoxicity. Naringin (NRG) is a natural, therapeutically active flavanone glycoside with anti-inflammatory, anti-apoptotic, and antioxidant. The current study was therefore designed to investigate the protective effect of NRG against the VPA-induced experimental hepatotoxicity model. For this purpose, 24 Wistar albino rats were randomly divided into three groups as control (Vehicle), VPA (500 mg/kg), and NRG + VPA (100 mg/kg NRG + 500 mg/kg VPA) groups. The agents were administered via oral gavage for 14 days. Blood and liver tissue samples were taken on the end of the experiment. Biochemical analyzes were performed on the blood and liver samples. Also, malondialdehyde (MDA), superoxide dismutase (SOD) enzyme, glutathione (GSH) content, catalase (CAT) enzyme levels were examined in the liver tissue samples. Histopathological changes (hydropic degeneration and congestion) in the VPA group were increased significantly when compared to the control group (p < 0.05). We also found a decrease in enzymes of serum liver function in the VPA group. However, NRG has been shown not to prevent histopathological changes in the VPA group. According to our results with this experiment protocol, NRG could not exert sufficient protection against VPA-induced hepatotoxicity.

Therapeutic effects of dexpanthenol on the cardiovascular and respiratory systems following cecal ligation and puncture-induced sepsis in rats.

Cecal ligation and puncture (CLP) is a commonly used model of sepsis in vivo. We investigated the effects of dexpanthenol (DXP) on heart, lung and aorta in CLP-induced sepsis in rats. Rats were divided into four groups of eight: group 1, sham (SH); group 2 (DXP), 500 mg/kg DXP injected intraperitoneally (i.p.); group 3 (CLP), CLP performed; group 4 (CLP + DXP), 500 mg/kg DXP injected i.p. after CLP. Heart, lung and aorta specimens were harvested for histopathological and biochemical analysis. Heart rate increased in group 3 compared to group 1; DXP administration to group 4 did not alleviate this change. In heart tissue samples, MDA levels were decreased significantly in groups 2 and 4 compared to group 3. The levels of GSH in groups 2 and 3 were elevated compared to groups 1 and 2. SOD activity was increased significantly in group 4 compared to group 3. CAT activity for group 4 was increased significantly compared to groups 1 and 3. We found that caspase-9 and caspase-3 activity was increased after application of CLP. Also, DXP treatment decreased the number of caspase-positive cells significantly compared to group 3. DXP appears to be promising for reducing sepsis-related mortality.