2-Arachidonoylglycerol Activity in Over Ischemia Reperfusion Damage: Can Endocannabinoids Protect Ovarian Reserve?

Objective: The present study aimed to demonstrate the possible effects of increased 2-arachidonoylglycerol (2-AG) by applying the monoacylglycerol lipase inhibitor KML-29 on rats with ovarian ischemia-reperfusion (IR) model. Methods: Forty-eight female Wistar albino rats were divided into six groups. Group 1: Sham, Group 2: Ischemia, Group 3: IR, Group 4: IR + KML-29 (2 mg/kg), Group 5: IR + KML-29 (20 mg/kg), and Group 6: IR + vehicle (dimethyl sulfoxide). Three hours of ischemia followed by 3 h of reperfusion. Two different doses of KML-29 (2 and 10 mg/kg) were administered intraperitoneally in Groups 4 and 5, 30 min before reperfusion. Ovarian IR injury and ovarian reserve were evaluated histopathological and by using nuclear factor (NF)-κB, interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß1, superoxide dismutase, glutathione peroxidase pre-/postoperative blood antimullerian hormone, and inhibin B. Results: In the KML-1 and KML-2 groups, this damage was significantly reduced compared to the ischemia group. NF-κB, IL-1ß, TNF-α, and TGF-ß1 immunoreactivities increased statistically significantly in the ischemia group compared to the control group (p<0.001). Immunoreactivities of these proteins were significantly decreased in the KML-1 and KML-2 groups (p<0.001). It was observed that the number of these apoptotic cells decreased significantly in the KML-1 and KML-2 groups compared to the ischemia group (p<0.001). The postoperative inhibin level showed a significant decrease in the ischemia group compared to the sham group, while a significant increase was observed in the KML-1 and KML-2 groups compared to the ischemia group. Conclusion: It was seen that anti-inflammatory, antioxidant, and antiapoptotic activity was formed, and the ovarian reserve was preserved with 2-AG in ovarian IR damage. The protective effect of endocannabinoids on the ovaries may create a promising new treatment strategy for many pathologies that will affect the ovarian reserve.

Neuroprotective effect of transient receptor potential Vanilloid 1 agonist capsaicin in Alzheimer's disease model induced with okadaic acid.

BACKGROUND: The presence of Transient Receptor Potential Vanilloid 1 (TRPV1) channels was detected in many regions of the human and rat brain, including the cortex and hippocampus. TRPV1 channels have functions such as the modulation of synaptic transmission and plasticity and the regulation of cognitive functions. Previous studies conducted with TRPV1 agonists and antagonists show that this channel is associated with the neurodegenerative process. In the present study, the purpose was to investigate the effects of capsaicin, which is a TRPV1 agonist, and capsazepine, a TRPV1 antagonist, in the Alzheimer's Disease (AD) model that was induced by intracerebroventricular (ICV) administration of okadaic acid (OKA). METHODS: The AD-like experimental model was created with bilateral ICV OKA injection. Intraperitoneal capsaicin and capsazepine injections were administered to the treatment groups for 13 days and histological and immunohistochemical examinations were performed from the cortex and hippocampal CA3 regions of the brain. The Morris Water Maze Test was used for spatial memory measurement. RESULTS: ICV OKA administration increased the levels of caspase-3, phosphorylated-tau-(ser396), Aß, TNF-α, and IL1-ß, from the cortex and hippocampal CA3 regions of the brain and decreased the phosphorylated-Glycogen synthase kinase-3 beta-(ser9) levels. In addition, the OKA administration corrupted the spatial memory. The TRPV1 agonist capsaicin reversed the pathological changes induced by ICV OKA administration, but not the TRPV1 antagonist capsazepine. CONCLUSIONS: It was found in the study that the administration of the TRPV1 agonist capsaicin reduced neurodegeneration, neuroinflammation, and deterioration in spatial memory in the AD model induced by OKA.

The protective effect of JZL184 on ovarian ischemia reperfusion injury and ovarian reserve in rats.

AIM: Ovarian torsion is a gynecopathology that requires emergency surgery in women. However, ischemia reperfusion injury (IRI) occurs after treatment with detorsion. This study aimed to evaluate the effects of monoacylglycerol lipase inhibitor JZL184 on ovarian IRI and ovarian reserve. METHODS: Forty-eight female Wistar albino rats were divided into six groups. Group 1: Sham, Group 2: Ischemia, Group 3: ischemia/reperfusion (IR), Group 4: IR + JZL184 4 mg/kg, Group 5: IR + JZL184 16 mg/kg, Group 6: IR + vehicle (dimethyl sulfoxide). Three hours of ischemia followed by 3 h of reperfusion. Two different doses of JZL184 (4 and 16 mg/kg) were administered intraperitoneally in Group 4 and 5, 30 min before reperfusion. Ovarian IRI and ovarian reserve were evaluated in serum and tissue by using histopathological and biochemical parameters. RESULTS: Treatment with JZL184 was associated with a significant increase in ovarian 2-arachidonoylglycerol and improved serum anti-Mullerian hormone, Inhibin B, primordial follicle count, and ovarian histopathological damage score (p < 0.05). JZL184 treatment significantly decreased the level of malondialdehyde, and increased superoxide dismutase enzyme activity and glutathione (GSH) levels (p < 0.05). The increased phosphorile nuclear factor-κB (Phospho-NF-κB-p65), tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1ß), transforming growth factor beta 1 (TGF-ß1), and TUNEL assay immunopositivity scores in ovarian I/R injury were decreased after treatment with JZL184 (p < 0.05). CONCLUSIONS: JZL184 showed significant ameliorative effects on ovarian IRI and ovarian reserve caused by IR through acting as an antioxidant, anti-inflammatory, and antiapoptotic agent. Thus, JZL184 may be a novel therapeutic agent for ovarian IRI.

The effects of pirfenidone on T helper cells in prevention of intraperitoneal adhesions.

Abdominal surgery is linked with peritoneal adhesions. We investigated that the anti-fibrotic agent pirfenidone (PFD) has immune modulating activities and evaluated its effects on the function of T helper type 1 (Th1), Th2 and T regulatory (Treg) cells, which may play important roles in peritoneal adhesions. Eighteen female Wistar rats underwent right-sided parietal peritoneal and right uterine horn adhesion model. Rats were randomized into 3 groups as group 1 (control) (closure of midline abdominal incision without any agent administrations), group 2 (closure of incision after intraperitoneal administration of PFD) and group 3 (closure of incision and only oral administration of PFD for 14 days). Relaparotomy was performed 14 days after the first surgery. Effect of PFD on adhesion formation was assessed on Th1, Th2 and Treg cells counts using Anti-T-bet, Anti-GATA-3 Anti-FOXP3 antibodies respectively. Th1 counts were moderate in the control group, and didn't show a significant difference between all groups. Th2 cell counts were very high in the control group, but both intraperitoneal and oral administration of PFD resulted in a significant reduction in Th2 cell counts. Treg cell counts were low in number in the control group. In the intraperitoneal administration of PFD group, Treg cell counts were significantly lower than control group. There was no difference of the Treg cells between control groups and the oral administration of PFD group. PFD has prevention effect on intraperitoneal adhesions. This prevention effect seems to be related with the reduction in the numbers of Th2 and Treg cells.

Effect of Pirfenidone on Vascular Proliferation, Inflammation and Fibrosis in an Abdominal Adhesion Rat Model.

AIM: To study the efficacy of pirfenidone for prevention of postoperative adhesion formation in an adhesion rat model. MATERIALS AND METHODS: Eighteen female Wistar rats were subjected to right-sided parietal peritoneum and right uterine horn adhesion model. Rats were randomized into three groups: group 1 (control) (closure of midline abdominal incision without any agent administration), group 2 (closure of incision after intraperitoneal administration of pirfenidone), and group 3 (closure of incision and only oral administration of pirfenidone for 14 days). Relaparotomy was performed 14 days after the first surgery. Effect of pirfenidone on adhesion formation was assessed on light microscopy by scoring vascular proliferation, inflammation, fibrosis, and collagen formation in the scarred tissue. Effect of pirfenidone on inflammation was assessed by measurement of transforming growth factor-ß and interleukin-17 levels in scarred tissue. RESULTS: The degree of vascular proliferation (1.32 ± 0.39 versus 2.34 ± 0.46, p < 0.001), inflammation (1.60 ± 0.70 versus 2.60 ± 0.52, p < 0.01), and fibrosis (1.50 ± 0.53 versus 2.40 ± 0.52, p < 0.01) were less prominent in group 2 compared to group 1, respectively. Only vascular proliferation was found to be less prominent in group 3 compared to group 1 (1.60 ± 0.42 versus 2.34 ± 0.46, p < 0.01). Intraperitoneal and oral administration of pirfenidone reduced tissue levels of inflammatory markers (TGF-ß and IL-17) in parietal and visceral peritoneum compared to control group. Intraperitoneal administration of pirfenidone compared to oral administration was more effective in reducing tissue levels of inflammatory markers. CONCLUSION: Pirfenidone is an effective agent on the prevention of postoperative vascular proliferation, inflammation and fibrosis in scarred tissue particularly with intraperitoneal administration.

Matrix changes due to the toxic effects of metronidazole in intestinal tissue of fish (Onchorhynchus mykiss).

Metranidazole (MTZ) is an antibiotic used for parasitic infections in a number of species. Accumulation of this drug in the environment and its interaction with fish of economic value makes this drug particularly important. In the present study, we examined the histopathological effects of MTZ on the intestinal tissue of Oncorhynchus mykiss. The fish in aquarium were exposed to MTZ at doses of 5, 10, 20 mg/L for 2, 4 and 8 days. At the end of the experiments, macroscopic pathology or death were not observed at these doses. Histochemical staining with Haematoxylene-Eosin, Periodic Acid Schiff and Gomori Trichrome showed, depending on increased dose and prolonged duration, areas of necrosis, edema, inflammation, small tears at the tips of the villi and excretion with heterogenic distribution of the Goblet cells. Moreover, changes in the connective tissue of the intestines due to toxicity of MTZ and decreases in immunostaining of matrix proteins such as laminin and collagen IV, especially in the epithelium were observed. Findings of the present study would be useful to demonstrate the adverse effects of MTZ use, emphasizing the importance of the effect on fish which could be very important public health.

Effects of Ginkgo biloba on experimental rapid maxillary expansion model: a histomorphometric study.

OBJECTIVE: We aimed to investigate the effect of systemic Ginkgo biloba in rapid maxillary expansion (RME). STUDY DESIGN: We randomly divided 24 rats into 3 groups: expansion only (EO), expansion plus Ginkgo biloba (GB), and no expansion (NE). Expansion appliances were affixed to the maxillary incisors. After a 5-day expansion period, there was a consolidation period of 15 days, following which the rats were killed. Histomorphometric examination was performed to determine the number of osteoclasts, osteoblasts, and capillaries, the number and intensity of inflammatory cells, and new bone formation. RESULTS: New bone formation, number of capillaries, and the ratio of inflammatory cells in maxillary sutures were higher in the GB group than in the other groups. Statistical analysis demonstrated that the GB group had more osteoblasts and osteoclasts than the other groups. CONCLUSIONS: GB may hasten new bone regeneration in RME and prevent relapse after RME.

Thymoquinone accelerates new bone formation in the rapid maxillary expansion procedure.

OBJECTIVE: The aim of this study was to evaluate the effect of systemic thymoquinone (TQ) in a rat rapid maxillary expansion (RME) study. DESIGN: Thirty-two Wistar albino rats were divided into 4 equal groups: only-expansion (OE), expansion plus TQ (TQ1 group, TQ given to the rats during their nursery phase and during the expansion and retention period), expansion plus TQ (TQ2 group, TQ given to the rats only during the retention period), and control group (no procedure done). Expansion appliances were placed on the maxillary incisors of all animals for 5days. The appliance was deactivated during the 12day retention period. The rats were sacrificed at the end of the retention period. Histomorphometric evaluation was carried out in order to compare the number of osteoclasts, osteoblasts, and capillaries, as well as the intensities of inflammatory cells, and new bone formation amongst the groups. RESULTS: New bone formation, number of capillaries and the ratio of intensities of inflammatory cells in maxillary sutures was higher in the TQ groups than in the other groups. Statistical analysis also demonstrated that osteoblast and osteoclast numbers were also highest in the TQ1 group. CONCLUSION: Histomorphometric analysis demonstrated that systemic use of thymoquinone may be effective in accelerating new bone formation in the RME procedure and that TQ may be beneficial in preventing relapse following the RME procedure.

Metrical and histological investigation of the effects of low-level laser therapy on orthodontic tooth movement.

The aim of this study was to evaluate the effects of 820-nm diode laser on osteoclastic and osteoblastic cell proliferation-activity and RANKL/OPG release during orthodontic tooth movement. Thirty-eight albino Wistar rats were used for this experiment. Maxillary incisors of the subjects were moved orthodontically by a helical spring with force of 20 g. An 820-nm Ga-Al-As diode laser with an output power of 100 mW and a fiber probe with spot size of 2 mm in diameter were used for laser treatment and irradiations were performed on 5 points at the distal side of the tooth root on the first, second, and 3rd days of the experiment. Total laser energy of 54 J (100 mW, 3.18 W/cm(2), 1717.2 J/cm(2)) was applied to group II and a total of 15 J (100 mW, 3.18 W/cm(2), 477 J/cm(2)) to group III. The experiment lasted for 8 days. The number of osteoclasts, osteoblasts, inflammatory cells and capillaries, and new bone formation were evaluated histologically. Besides immunohistochemical staining of PCNA, RANKL and OPG were also performed. No statistical difference was found for the amount of tooth movement in between the control and study groups (p > 0.05). The number of osteoclasts, osteoblasts, inflammatory cells, capillary vascularization, and new bone formation were found to be increased significantly in group II (p < 0.05). Immunohistochemical staining findings showed that RANKL immunoreactivity was stronger in group II than in the other groups. As to OPG immunoreactivity, no difference was found between the groups. Immunohistochemical parameters were higher in group III than in group I, while both were lower than group II. On the basis of these findings, low-level laser irradiation accelerates the bone remodeling process by stimulating osteoblastic and osteoclastic cell proliferation and function during orthodontic tooth movement.