FGF-18 alleviates memory impairments and neuropathological changes in a rat model of Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial pathology marked by amyloid beta (Aß) accumulation, tau hyperphosphorylation, and progressive cognitive decline. Previous studies show that fibroblast growth factor 18 (FGF18) exerts a neuroprotective effect in experimental models of neurodegeneration; however, how it affects AD pathology remains unknown. This study aimed to ascertain the impact of FGF18 on the behavioral and neuropathological changes in the rat model of sporadic AD induced by intracerebroventricular (ICV) injection of streptozotocin (STZ). The rats were treated with FGF18 (0.94 and 1.88 pmol, ICV) on the 15th day after STZ injection. Their cognitive function was assessed in the Morris water maze and passive avoidance tests for 5 days from the 16th to the 21st days. Aß levels and histological signs of neurotoxicity were detected using the enzyme-linked immunosorbent assay (ELISA) assay and histopathological analysis of the brain, respectively. FGF18 mildly ameliorated the STZ-induced cognitive impairment; the Aß accumulation was reduced; and the neuronal damage including pyknosis and apoptosis was alleviated in the rat brain. This study highlights the promising therapeutic potential for FGF18 in managing AD.

Protective effect of ursodeoxycholic acid and resveratrol against tacrolimus induced hepatotoxicity.

Tacrolimus (TAC) is a potent and well-tolerated immunosuppressive drug, but serious side effects including nephrotoxicity and hepatotoxicity have been reported. Ursodeoxycholic acid (UDCA) and resveratrol (RSV) exhibit hepatoprotective effects in liver diseases. We investigated the hepatoprotective effect of UDCA and RSV against TAC induced hepatotoxicity. We divided 40 male rats into five equal groups: A) control group, B) TAC group, C) TAC + UDCA group, D) TAC + RSV group, E) TAC + UDCA + RSV group. We administered 0.5 mg/kg TAC once daily, 25 mg/kg UDCA twice daily and 10 mg/kg RSV once daily. The drugs in the experimental groups were given by gavage from the first day of the study and continued for 21 days. Histopathologic and biochemical analyses were performed on day 22. In group B, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), total oxidative status (TOS) and malondialdehyde (MDA) levels were higher compared to group A, and catalase (CAT), superoxide dismutase (SOD) levels and total antioxidant status (TAS) were lower compared to group A. Severe cellular swelling, degeneration and focal necrosis were more evident in group B than in groups C-E. Histopathological improvement was observed in groups C-E, where UDCA and RSV were combined, compared to group B. We found that UDCA and RSV, together or separately, protected the liver against oxidative stress damage caused by TAC.

Galium aparine L. protects against acetaminophen-induced hepatotoxicity in rats.

The toxicity of acetaminophen (N-acetyl-para-aminophenol (APAP)) is the most frequent cause of drug-induced liver damage. Galium aparine L. (GA) is traditionally used to treat jaundice. We aimed to investigate the hepatoprotective potential of GA in the APAP-induced hepatic encephalopathy (HE) rat model. Qualitative phytochemical characterization of GA was performed by LC/Q-TOF/MS analysis. Wistar rats were pretreated with GA (250 and 500 mg/kg b.wt. per oral) for five days. On the 6th day, the rats were exposed to APAP (1500 mg/kg b.wt. oral gavage) and behavioral tests (open field and passive avoidance tests) were applied on the 7th and 8th days. The animals were killed, and biochemical and histopathological parameters were assessed in blood and hepatic specimens. GA pretreated rats exhibited a significant reduction in APAP-induced liver damage, evidenced by the reduction in liver necrosis and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin (BIL). GA demonstrated an anxiolytic effect, as seen in the acquisition trial and grooming behavior. The short-term memory performances of animals were not changed in all groups, suggesting that APAP intoxication did not affect hippocampal function. These results show that GA extract markedly exerts hepatoprotective activity, while its effect on hepatic encephalopathy was limited.

The 5-HT7 receptor antagonist SB-269970 alleviates seizure activity and downregulates hippocampal c-Fos expression in pentylenetetrazole-induced kindled rats.

OBJECTIVES: Recently, studies have demonstrated that serotonin type 7 receptors (5-HT7) have conflincting effects on neuronal excitability in different brain regions. However, the effect of 5-HT7 on seizures has not been exactly elucidated yet. Therefore, our aim in this study was to investigate the effects of 5-HT7 antagonist SB-269970 on pentylenetetrazole (PTZ) induced fully kindled rats. METHODS: In the study, 32 adult male Wistar Albino rats (weighing 220-260 g) were used. Rats were injected with PTZ (35 mg/kg) intraperitoneally every other day to generate kindling model. 5-CT (0.1 mg/kg) and SB-269970 (1 mg/kg) were administered 30 min before acute seizure induction with PTZ (35 mg/kg). Seizure stages were determined according to the Racine scale. After electrocorticography (ECoG) recordings of seizure-induced rats were obtained, the animals were sacrificed by decapitation. The hippocampal GABA levels were determined by ELISA kit and the number of c-Fos positive neurons in the hippocampal dentate gyrus (DG), CA1 and CA3 areas were measured by immunohistochemical method. RESULTS: The results showed that SB-269970 reduced the number of spikes, percent seizure duration and duration of generalized tonic-clonic seizures (dGTCS), while increasing the onset time of generalized tonic-clonic seizures (oGTCS). The hippocampal GABA levels were significantly increased in the SB-269970 group compared with the PTZ group. In addition, SB-269970 reduced the number of c-Fos positive cells in hippocampal CA1 area. DISCUSSION: 5-HT7 antagonist SB-269970 displays anticonvulsant effects on PTZ-induced seizures in fully kindled rats and these effects may be related to GABAergic activity in the hippocampus.

Investigation of the mechanisms involved in anticancer effect of glucosamine sulfate on SH-SY5Y cell line.

AIM: Glucosamine derivatives have been found to have anticancer effects in many cancer cell lines in previous investigations. The effect of glucosamine sulfate on neuroblastoma, however, is uncertain. The potential cytotoxic effects of glucosamine sulfate on the SH-SY5Y cell line were investigated in this study. The underlying mechanisms of this cytotoxicity have also been studied. MATERIAL AND METHODS: In this study, the SH-SY5Y cell lines were used. The cells were treated with various concentrations of glucosamine sulfate (0.3125, 0.625, 1.25 and 2.5 µg/mL) and the viability of the cells was determined using the XTT assay after 24 hours. The quantities of cleaved PARP, BCL-2, 8-Hydroxy-desoxyguanosine (8-oxo-dG), cleaved caspase 3, Bax, total oxidant, and total antioxidant in the cells were determined by ELISA kits. RESULTS: At doses of 0.3125, 0.625, 1.25 and 2.5 µg/mL, glucosamine sulfate dramatically reduced cell viability in SH-SY5Y cells (p<0.001). ELISA tests demonstrated that 1.25 µg/mL glucosamine sulfate considerably increased the amounts of 8-oxo-dG, cleaved caspase 3, Bax, cleaved PARP and total oxidant. However, 1.25 µg/mL glucosamine sulfate treatment did not change the quantity of BCL-2 protein. CONCLUSIONS: Altogether, glucosamine sulfate produced considerable cytotoxicity in SH-SY5Y cells by triggering oxidative stress, inducing DNA damage, and finally causing apoptosis. In addition, more research is needed to determine the efficacy of glucosamine sulfate as an anticancer drug in the treatment of neuroblastoma (Fig. 5, Ref. 39).

Captopril exhibits protective effects through anti-inflammatory and anti-apoptotic pathways against hydrogen peroxide-induced oxidative stress in C6 glioma cells.

Recent studies have shown that angiotensin-converting enzyme (ACE) inhibitors have reduced oxidative damage in the central nervous system (CNS). Accumulating evidence have also demonstrated that captopril, an ACE inhibitor, has protective effects on the CNS. However, its effects on hydrogen peroxide (H2O2)-induced oxidative damage in glial cells and interaction with the inflammatory system are still uncertain. Therefore, this study was aimed to investigate the protective effect of captopril on glial cell damage after H2O2-induced oxidative stress involved in the inflammatory and apoptotic pathways. The control group was without any treatment, and the H2O2 group was treated with 0.5 mM H2O2 for 24 h. The captopril group was treated with various concentrations of captopril for 24 h. The captopril + H2O2 group was pre-treated with captopril for 1 h and then exposed to 0.5 mM H2O2 for 24 h. In the captopril + H2O2 group, captopril at all concentrations significantly increased the cell viability in C6 cells. It also significantly increased the TAS and decreased the TOS levels which are an indicator of oxidative stress. Moreover, captopril significantly reduced the inflammation markers including NF-kB, IL-1 ß, COX-1, and COX-2 levels. Flow cytometry results also exhibited that captopril pretreatment significantly decreased the apoptosis rate. Besides, captopril significantly reduced apoptotic Bax and raised anti-apoptotic Bcl-2 protein levels. In conclusion, captopril has protective effects on C6 cells after H2O2-induced oxidative damage by inhibiting oxidative stress, inflammation, and apoptosis. However, further studies need to be conducted to evaluate the potential of captopril as a neuroprotective agent.

The Effects of Proton Pump Inhibitors (Pantoprazole) on Pentylenetetrazole-Induced Epileptic Seizures in Rats and Neurotoxicity in the SH-SY5Y Human Neuroblastoma Cell Line.

Recent studies have shown that proton pump inhibitors have positive effects on the nervous system. However, its effect on epileptic seizure and neuronal damage are still unclear. In this study, it was aimed to investigate the effect of pantoprazole on pentylenetetrazole-induced epileptic seizures in rats and neurotoxicity in the SH-SY5Y cell line. Animals were divided into three groups: control, saline (1 mL/kg serum physiologic), and pantoprazole (10 mg/kg). Pentylenetetrazole (45 mg/kg) was given to induce a seizure and a passive avoidance test trial was carried out to evaluate memory function. 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3, and brain-derived neurotrophic factor (BDNF) levels were measured in the brain by commercial kits. SH-SY5Y cells were treated with saline or pantoprazole for one hour, and then pentylenetetrazole (30 µm) was added to the medium to induce neurotoxicity. After 24 h, cell viability, total antioxidant, total oxidant status, and apoptosis were measured in SH-SY5Y cells. It was found that pantoprazole treatment postponed epileptic seizure onset, protected memory, reduced 8-OHdG, caspase-3, and also increased BDNF in the brain. In addition, it blocked pentylenetetrazole toxicity, apoptosis, increased antioxidant, and decreased oxidant status in SH-SY5Y cells. Pantoprazole significantly improved seizure, oxidative stress, and apoptosis. Thus, pantoprazole could be used as a supportive therapeutic agent in epilepsy.

Effect of lung resection on electrocardiography.

BACKGROUND: Post-operative changes in electrocardiography (ECG) after lung surgery have been investigated in prior researches. We have limited data about benign physiologic changes in ECG after lung surgery, specifically after lung resection. The aim of our study was to investigate relationship in between lung resection with minimally invasive robotic or video-assisted thoracoscopic surgery (VATS) and its effect on ECG after lung resection. METHODS: After exclusion criteria had been applied, a total of 133 patients were enrolled in the present study. Operational information such as amount of resected segment and side of resection was recorded. Lung resections were divided into two groups. One group included surgeries with lung resections <3 segments and other group included surgeries with segmentectomy ≥3 segments. Pre-operative and postoperative (in between 2nd and 3rd months) ECG data of the patients were compared. The location of resected segments as left-sided and right-sided resections were noted to compare the ECG changes for sub-analysis. RESULTS: Among 133 patients, 101 patients were male (75.9%). There was no significant difference between parameters including ventricular rate, P wave, QRS wave and T wave axis in degrees, PR, QRS, QT and QTc durations, Tpe interval, ratio of Tpe interval to QT and QTc interval and fQRSTa. There was significant difference between before and after resection in terms of degree of QRS axis (before resection =37.3 ± 52.7 vs. after resection = 26.2 ± 55.7, P = .026). Sub-analysis regarding to amount of resected segments, there was no significant difference identified in terms of QRS axis in degrees between before and after resection for patients who underwent lung resection <3 segments (p = .885). However, there was significant difference in QRS axis in degrees for patients who underwent lung resection ≥3 segments (before resection = 47.3 ± 57.5 vs. after resection = 23.7 ± 66.2, P = .010). There was significant rightward axial change after left-sided lung resections (before resection =32.0 ± 52.4 vs. after resection = 49.4 ± 47.1, P = .005) and leftward axial change after right-sided lung resection (before resection = 41.7 ± 53.0 vs. after resection = 7.1 ± 55.2, P < .001). CONCLUSION: Understanding and recognition of possible ECG changes are crucial during post-operative follow-up of the patients who underwent lung resection. These changes might be benign changes, which are related to anatomical and geometrical changes within thoracic cavity.

The effects of long-term grazing exclosures on range plants in the Central Anatolian Region of Turkey.

Over the last fifty years, almost half of the steppe rangeland in the Central Anatolian Region of Turkey (CAR) has been converted to cropland without an equivalent reduction in grazing animals. This shift has led to heavy grazing pressure on rangeland vegetation. A study was initiated in June 2003 using 6 multiscale Modified-Whittaker plots to determine differences in plant composition between areas that have not been grazed in 27 years with neighboring grazed plant communities. A total of 113 plant species were identified in the study area with the ungrazed plots containing 32 plants more than the grazed plots. The major species were Astragalus acicularis, Bromus tomentellus, Festuca valesiaca, Genista albida, Globularia orientalis, Poa bulbosa, and Thymus spyleus ssp rosulans. Grazing impacts on forbs were more pronounced than for grasses and shrubs. Based on Jaccard's index, there was only a 37% similarity of plant species between the two treatments. Our study led to four generalizations about the current grazing regime and long-term exclosures in the steppe rangeland around the study area: (1) exclosures will increase species richness, (2) heavy grazing may have removed some plant species, (3) complete protection from grazing for a prolonged period of time after a long history of grazing disturbance may not lead to an increase in desirable plant species with a concomitant improvement in range condition, and (4) research needs to be conducted to determine how these rangelands can be improved.