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The anti‐catabolic bisphosphonate alendronate is considered as the first‐line medical treatment in post‐menopausal osteoporosis; but several side effects, including gastric mucosal injury, are associated with its use. The aim was to elucidate whether combined treatment with melatonin plus alendronate would be more advantageous in the maintenance of bone and the prevention of gastric side effects. Under anaesthesia, female Sprague‐Dawley rats underwent bilateral ovariectomy (OVX), while control group had sham surgery. Four weeks after the surgery, OVX rats were treated with saline, melatonin (25 μg/mL/d), alendronate (70 μg/kg/wk), melatonin + alendronate, melatonin + melatonin receptor antagonist (luzindole, 10 μg/kg/d) or alendronate + melatonin + luzindole for 8 weeks. Rats were euthanized at the end of 12th week. Runx2 expression, apoptotic cells, and trabecular thickness were evaluated in tibiae, while gastric tissues were analysed for oxidative injury parameters. In all OVX groups, Runx2 expression was depressed. Saline‐treated OVX group presented an extreme decrease in calcified area in opposition to melatonin‐ or alendronate‐treated groups, while the bones in alendronate + melatonin‐treated group were similar to those of the sham‐operated group. Concomitant with the improvements examined histologically in bone tissues, quantitative TUNEL (+) cells were similarly lower in alendronate‐ or melatonin‐treated groups. Oxidative gastric damage was increased in saline‐ or alendronate‐treated groups, which were depressed in the presence of melatonin. Although melatonin and alendronate exerted similar supportive effects on the maintenance of bone mass, melatonin may have a more advantageous impact by protecting against OVX‐induced gastric injury, which was aggravated by alendronate use. Highlights: Our results demonstrate that alendronate and melatonin had similar supportive effects on the maintenance of bone mass, while melatonin prevented the gastric side effects of alendronate, making this combination an advisable therapeutic approach in the treatment of menopausal osteoporosis. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to investigate electrophysiologically and histopathologically, the protective effects of intratympanic memantine, an N-methyl-D-aspartate receptor antagonist, on ototoxicity caused by cisplatin, an anti-neoplastic agent used in many types of cancer. Methods: Thirty-seven guinea pigs with a normal auditory function were randomly allocated to group 1 (cisplatin; n = 8), group 2 (memantine; n = 8), group 3 (cisplatin + memantine; n = 8), group 4 (cisplatin + physiological serum [PS]; n = 8), and group 5 (control; n = 5). Auditory assessments were conducted using distortion product otoacoustic emissions (DPOAE) within a frequency range of 1–32 kHz and auditory brainstem responses (ABRs) within 8–32 kHz. A single dose of cisplatin (12 mg/kg) was administered intraperitoneally, followed by intratympanic administration of 0.2 mL of either memantine or PS to both ears at least half an hour before cisplatin administration. Subsequent auditory evaluations were conducted 72 h after cisplatin administration. Histopathological analyses were performed using light microscopy of the right ear and scanning electron microscopy (SEM) of the left ear. Results: Auditory evaluations conducted before and after treatment revealed significant findings. Specifically, within groups 3 and 4, ABR thresholds were elevated at all frequencies (p = 0.00), whereas the DPOAE signal-to-noise ratios were reduced at frequencies of 8, 12, 16, and 24 kHz (p = 0.001, p = 0.01, p = 0.01, and p = 0.00, respectively). Histopathologically, both light microscopy and SEM revealed that the cisplatin + memantine group exhibited fewer hair cells and nuclear degeneration in the spiral ganglion than the cisplatin and cisplatin + PS groups. Additionally, the stria vascularis thickness was greater in the cisplatin + memantine group than in cisplatin and cisplatin + PS groups. Conclusion: Despite the negative electrophysiological findings, the histopathological outcomes suggest that intratympanic memantine may have a potential protective effect against cisplatin-induced ototoxicity. However, further investigations are warranted to corroborate these findings and elucidate the underlying mechanisms of action of memantine. [ABSTRACT FROM AUTHOR]

Background  Vasospasm is a major problem following microsurgical reconstruction which can result in the partial or complete loss of the flap tissue. The aim of this study was to investigate the efficiency of hydrodilatation for the prevention of vasospasm. Methods  Thirty male Wistar rats were used for this experimental study. Femoral arteries of were exposed, photographed, and transected. In group 1, group 2, and group 3 papaverine solution, hydrodilatation, and minimal mechanical dilatation (control group) was performed, respectively. The anastomosis was completed and the arteries were photographed again 10 minutes after completion of the anastomosis. Following 7-day period samples for transmission electron microscopy (TEM) and light microscopy were obtained. Results  The mean vessel diameters prior to transection were 0.43, 0.45, and 0.52 mm in the papaverine, hydrodilatation, and control groups, respectively. The mean vessel diameter 10 minutes following the completion of anastomosis was 0.76, 0.75, and 0.51 mm in the papaverine, hydrodilatation, and control groups, respectively. Median score for papaverine group regarding histological parameters of regular endothelial lining and lumen, neutrophil infiltration, vascular congestion, and edema in tunica adventitia was 2, 3, 2, and 3 positive, respectively. Median score for the papaverine group regarding histological parameters of regular endothelial lining and lumen, neutrophil infiltration, vascular congestion, and edema in tunica adventitia was 3, 3, 3, and 3 positive, respectively. All the histological scores were negative in the control group. The difference between the control group and the experiment groups 1 and 2 was significant regarding all four histological parameters (p  < 0.05). Conclusion  Hydrodilatation and papaverine application were both effective in preventing vasospasm following microsurgical intervention but papaverine caused slightly less damage to the endothelial lining and less edema in the tunica adventitia when compared with the hydrodilatation. Hydrodilatation group showed a vasodilatory effect that was statistically similar to that of papaverine, which has a proven efficacy. [ABSTRACT FROM AUTHOR]

Objective: Metabolic disorders occurring in post-menopausal period increase the risk for development of fatty liver disease in women. Aim of the study was to evaluate possible effects of ghrelin on metabolic biomarkers and hepatic morphology in ovariectomized (OVT) rats. Methods:Under ketamine-chlorpromazine anesthesia (100 mg/kg, 0.75 mg/kg), Sprague-Dawley rats (n=12) underwent bilateral OVT, while control group had sham-surgery (n=6). Four weeks after surgery, half of OVT rats were treated intraperitonally with ghrelin (1 mg/kg/hafta) for 4 weeks, while others were not treated. Rats were euthanized by cardiac puncture at the end of 8th weeks, and serum levels of glucose, insulin, aspartate aminotransferase (AST), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), triglycerides, estradiol and progesterone were measured by an automated analyzer. Results: Increased body weights in OVT rats (p<0.001) recorded at the end of 2 months was not changed with ghrelin. Serum estradiol and progesterone levels were reduced (p<0.05) verifying altered gonadal hormone status, but insulin and glucose levels were not changed. Reduced HDL and increased LDL levels (p<0.0.5) were evident in non-treated OVX rats, while ghrelin treatment depressed LDL levels (p<0.0.5), but did not change HDL levels. However, ghrelin in OVT rats depressed triglycerides, VLDL and AST levels significantly (p<0.05). Moderate sinusoidal congestion, activated Kupffer cells and hepatocytes with ballooning degeneration was observed in non-treated OVT rats, while significant improvements were present in livers of ghrelintreated rats. Conclusion: In conclusion, mild dyslipidemia and hepatic degeneration in early post-menopausal period appear to be attenuated by ghrelin treatment, and require further investigation. [ABSTRACT FROM AUTHOR]

The prothrombotic and inflammatory state plays a significant role in the occurrence of cardiovascular complications in type 2 diabetes mellitus. In this study, the antidiabetic, anti‐inflammatory, and antiplatelet potentials of the extracts obtained from Ribes rubrum were investigated. The antidiabetic, anti‐inflammatory, and antioxidant activities of the ethanol and water extracts of R. rubrum were evaluated by in vitro methods. The total phenolic and flavonoid contents were also determined. The experimental diabetes model in rats was induced with streptozotocin (STZ). After hyperglycemia occurred, the ethanol extracts of R. rubrum (RRE, at 100 mg/kg and 500 mg/kg doses) were administered to the treatment groups for 14 days. Blood glucose, lipid profile, plasma, and pancreas tumor necrosis factor‐α (TNF‐α) levels were determined and compared at the end of the experiments. P‐selectin levels and mitochondrial membrane polarization (MMP) of platelets were also measured. In vitro study, the RRE showed potent anti‐inflammatory activity. Administration of RRE (at 100 mg/kg doses) to diabetic rats lowered blood glucose level insignificantly. The results showed that there was an increment in levels of TNF‐α in plasma and pancreas tissue of the diabetic group compared to the control group. R. rubrum extract regulated and normalized their levels in plasma and pancreatic tissue. RRE at both doses significantly decreased platelet P‐selectin levels and prevented STZ‐induced loss of MMP in platelets. The results of current research indicate that RRE extract has potent anti‐platelet and anti‐inflammatory effects and may be beneficial in preventing diabetic complications. Practical applications: Hyperglycemia causes dyslipidemia, advanced oxidative stress, platelet activation, and inflammation in diabetes mellitus. Plants with various medicinal properties are of worldwide interest for the treatment of diseases due to their biological activities. In this study, the antidiabetic, anti‐inflammatory, and antioxidant effects of extracts of Ribes rubrum (%100 ethanol, 50% ethanol, water) were evaluated by in vitro and in vivo methods. The diabetes model was induced with streptozotocin (STZ). The rats were divided into control, diabetic control, R. rubrum‐100 mg/kg, and R. rubrum‐500 mg/kg doses groups. Blood glucose levels, tumor necrosis factor‐α (TNF‐α), platelet P‐selectin levels, mitochondrial membrane polarization of platelets were examined. The present study has shown that R. rubrum has anti‐inflammatory and antiplatelet activity. R. rubrum may be beneficial in the prevention and treatment of DM complications due to its anti‐inflammatory and antithrombotic effects. [ABSTRACT FROM AUTHOR]

Our aim was to investigate the probable protective effects of aerobic, resistance and combined exercise methods on ovariectomy and d -galactose induced Alzheimer’s Disease (AD)-like model. d -galactose (100 mg/kg) or saline were administered intraperitoneally for 6 weeks to ovariectomized or sham-operated rats (n = 8/group). Aerobic (AE), resistance (RE) and combined exercises (CE) (aerobic + resistance) were performed for 3 times a week for 6 weeks. Anxiety level and cognitive functions were evaluated via hole-board and object recognition tests. Brain myeloperoxidase, malondialdehyde, nitric oxide activity, lucigenin-enhanced chemiluminescence, glutathione and serum insulin like growth factor-I (IGF-I) assays were done. Hippocampal mRNA levels of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and amyloid precursor protein 695 (APP695) were measured. Amyloid Beta (Aβ), NGF, BDNF, IGF-I immunoreactive neurons were evaluated. Freezing time were increased in AD-like model and decreased back with AE (p < 0.05). Deteriorated working memory in AD-like model was improved with all exercise types (p < 0.05-0.001). Reduced glutathione levels in AD-like model were increased and increased malondialdehyde levels were reduced and serum IGF-I levels were increased by all exercises (p < 0.05–0.001). Increased APP mRNA levels in AD-like model were decreased via CE (p < 0.05). Elevated Aβ scores in AD-like model were decreased by RE and CE (p < 0.01) in hippocampus and by all exercise types in cortex (p < 0.05–0.01). Decreased cortical NGF immunocytochemical scores of AD-like model were increased by CE (p < 0.05). Different exercise models may have protective effects in development stage of AD via reducing oxidative stress and Aβ scores, and by improving antioxidant system and brain plasticity. [ABSTRACT FROM AUTHOR]

Abstract: Oxidative stress has been implicated in various pathological processes including burn induced multiple organ damage. This study investigated the effects of lycopene treatment against oxidative injury in rats with thermal trauma. Under ether anesthesia, shaved dorsum of the rats was exposed to 90°C bath for 10s to induce burn and treated either vehicle (olive oil) or lycopene (50mg/kg orally). Rats were decapitated 48h after injury and the tissue samples from lung and kidney were taken for histological analysis and the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT) and caspase-3 activities. Proinflammatory cytokines, TNF-α and IL-1β, were assayed in blood samples. Severe skin scald injury caused a significant decrease in GSH levels, SOD and CAT activities, and significant increases in MDA levels, MPO and caspase-3 activities of tissues. Similarly, plasma TNF-α and IL-1β were elevated in the burn group as compared to the control group. Lycopene treatment reversed all these biochemical indices. According to the findings of the present study, lycopene possesses antiinflammatory, antiapoptotic and antioxidant effects that prevents burn-induced oxidative damage in remote organs. [Copyright &y& Elsevier]