The antioxidant, anti-inflammatory, and antiplatelet effects of Ribes rubrum L. fruit extract in the diabetic rats.

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.

The Efficacy of Hydrodilatation for the Prevention of Vasospasm following Microsurgical Anastomosis.

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.

Gamma-amino butyric acid immunoreactivity in the testis tissue of Wistar and genetic absence epilepsy rats / Inmunorreactividad del ácido gamma-amino butírico en el tejido testicular de ratas Wistar con epilepsia de ausencia genética

SUMMARY: Studies have shown the adverse effects of epileptic seizures on reproductive health. The aim of the present study was to investigate morphological changes, apoptosis and GABA localization in the testis tissue of genetic absence epilepsy rats. Testis tissues of GAERS and Wistar rats were processed for paraffin embedding and electron microscopy. Sections were stained with hematoxylin and eosin, Masson's trichrome and periodic acid-Schiff reaction. GABA immunohistochemistry was applied for determining the alterations in GABA levels. GABA immunoreactivity was observed in the seminiferous tubules and interstitial areas of both GAERS and Wistar rats. GABA immunoreactivity was found to be decreased in GAERS compared to Wistar group. Electron microscopic observations showed that GABA was present in manchette microtubules, sperm tail and neck at different phases of spermiogenesis. Qualitative observations revealed that testis tissues of GAERS showed reduced sperm in the seminiferous tubules compared to the Wistar controls. In conclusion, we demonstrated GABAergic system in the seminiferous tubules of control and GAERS rats, in parallel with the previous studies; and there were alterations in this system in GAERS. We suggest that these alterations in absence epilepsy may also affect the gonadal system, resulting in decreased sperm production.

RESUMEN: Los estudios han demostrado los efectos adversos de las convulsiones epilépticas sobre la salud reproductiva. El objetivo del presente estudio fue investigar los cambios morfológicos, la apoptosis y la localización de GABA en el tejido testicular de ratas con epilepsia de ausencia genética. Se procesaron tejidos testiculares de ratas GAERS y Wistar para inclusión en parafina y microscopía electrónica. Las secciones se tiñeron con hematoxilina y eosina, tricrómico de Masson y reacción de ácido peryódico de Schiff. Se aplicó inmunohistoquímica de GABA para determinar las alteraciones en los niveles de GABA. Se observó inmunorreactividad de GABA en los túbulos seminíferos y las áreas intersticiales de las ratas GAERS y Wistar. Se encontró que la inmunorreactividad de GABA estaba disminuida en GAERS en comparación con el grupo Wistar. Las observaciones microscópicas electrónicas mostraron que GABA estaba presente en los microtúbulos, la cola y el cuello del espermatozoide en diferentes fases de la espermiogénesis. Las observaciones cualitativas revelaron que los tejidos testiculares de GAERS mostraron una reducción de los espermatozoides en los túbulos seminíferos en comparación con los controles Wistar. En conclusión, demostramos el sistema GABAérgico en los túbulos seminíferos de ratas control y GAERS, en paralelo con estudios previos; y además se observaron alteraciones en este sistema en GAERS. Sugerimos que estas alteraciones en epilepisa de ausencia genética también pueden afectar el sistema gonadal, resultando en una disminución de la producción de semen.

Repeated Atmospheric Pressure Alteration Effect on the Cochlea in Rats: Experimental Animal Study.

OBJECTIVE: This study aimed to evaluate the effects of repeated pressure alterations on cochlear structures in rats in an attempt to understand indirectly the inner ear status of flight crew who are repeatedly exposed to pressure alterations.METHODS: There were 12 adult Wistar albino rats equally divided into 2 groups: Group 1 (controls) and Group 2 (study group). The animals in Group 2 were exposed to repeated pressure changes in a pressure cabin which is regulated by manometers. The animals in Group 1 were placed in the cabin without being exposed to pressure changes. Auditory brainstem response (ABR) testing was performed in all animals at the beginning and at the end of the study. After 12 wk the animals were sacrificed and their cochleas were investigated using scanning electron microscopy (SEM).RESULTS: In the study group, hearing decreases at 2 kHz, 4 kHz, 6 dB at 8 kHz, and 32 kHz were encountered at the end of 3 mo. On SEM evaluation of the control group, the outer hair cells (OHC) and stereocilia were normal throughout the cochlea. In the study group, there were irregularities in lateral surface connections and separations, collapse, and adhesions in the basal segment of the cochlea and partial loss of stereocilia throughout the cochlea.CONCLUSION: Repeated alterations in the atmospheric pressure can lead to damage in the inner ear with subtle or evident hearing loss. Frequent flyers like air workers may be at risk of inner ear damage, which may be considered an occupational health problem.Eroglu S, Dizdar HT, Cevizci R, Cengiz AB, Ogreden S, Bulut E, Ilgezdi S, Dilci A, Ustun S, Sirvanci S, Kaya OT, Bayazit D, Caki BO, Oktay MF, Bayazit Y. Repeated atmospheric pressure alteration effect on the cochlea in rats: experimental animal study. Aerosp Med Hum Perform. 2021; 92(7):550555.

The Role of Extracellular Vesicles Secreted From Thermal Stress-Induced Adipose-Derived Stem Cells on Bone Regeneration.

PURPOSE: Extracellular vesicles (EVs) are responsible for intercellular communication. Mesenchymal stem cell-derived vesicles have been shown to have similar properties as functional mesenchymal stem cells. The aim of this study was to compare the therapeutic benefit of EVs obtained from adipose tissue-derived stem cells (ADSC) on bone repair whereas using ß-tricalcium phosphate (ß-TCP) biomaterial as a carrier. MATERIALS AND METHOD: A single critical size bone defect of 8 mm in diameter was created on the right side of rat calvarium using a custom-made punch needle. Animals were randomly divided into 5 groups: group 1 (no treatment), group 2 (bone graft), group 3 (ß-TCP + ADSC), group 4 (ß-TCP + EV), group 5 (ß-TCP). Eight weeks later, animals were sacrificed and histologic and radiologic evaluation was performed. RESULTS: Semiquantitative histologic scoring demonstrated significantly higher bone regeneration scores for groups 2, 3, and 4 compared to group 1. Radiologic imaging showed significantly higher bone mineral density for groups 2, 3, and 5 compared to group 1. There were no significant differences between treatment groups in either histologic or radiologic scoring. CONCLUSIONS: Our data showed that EVs provided from thermally induced ADSCs did not show any significant difference in bone regeneration when compared to ADSCs themselves. Future studies should focus on determining the optimum amount and content of EV application since these vary significantly depending on the microenvironment.

Investigation of possible neuroprotective effects of some plant extracts on brain in bile duct ligated rats.

This study aimed to investigate the possible neuroprotective effects of bitter melon (BM), chard, and parsley extracts on oxidative damage that may occur in the brain of rats with bile duct ligation (BDL)-induced biliary cirrhosis. It was observed that lipid peroxidation (LPO), sialic acid (SA), and nitric oxide (NO) levels increased; glutathione (GSH) levels, catalase (CAT) activity, and tissue factor (TF) activity decreased significantly in the BDL group. However, in groups with BDL given BM, chard, and parsley extracts LPO, SA, NO levels decreased; GSH levels and CAT activities increased significantly. No significant differences were observed between groups in total protein, glutathione-S-transferase, superoxide dismutase, and boron. Histological findings were supported by the biochemical results. BM, chard, and parsley extracts were effective in the regression of oxidant damage caused by cirrhosis in the brain tissues. PRACTICAL APPLICATIONS: Bitter melon (BM), chard, and parsley have antioxidant properties due to their bioactive compounds which are involved in scavenging free radicals, suppressing their production, and stimulating the production of endogenous antioxidant compounds. Since BM, chard, and parsley extracts were found to be effective in the regression of oxidant damage caused by cirrhosis in the brain tissues, these plant extracts may be an alternative in the development of different treatment approaches against brain damage in cirrhosis. At the same time, these species have been used as food by the people for many years. Therefore, they can be used safely as neuroprotective agents in treatment.

Neurogenesis is Enhanced in Young Rats with Genetic Absence Epilepsy: An Immuno-electron Microscopic Study.

AIM: To investigate neurogenesis in both adult and 3-week-old genetic absence epilepsy rats from Strasbourg (GAERS) to determine if newly formed neurons within the dentate gyrus (DG) form synaptic contacts with GABAergic (gamma aminobutyric acid) and glutamatergic nerve terminals and compared to the control (non-GAERS) Wistar rats. MATERIAL AND METHODS: Brain tissue was processed for electron microscopic assessment. Thin sections from the hippocampal DG were double-labelled for anti-GABA or anti-VGLUT1 (vesicular glutamate transporter 1) and anti-doublecortin (DCX) antibodies using immunogold methodology and examined with the transmission electron microscope for morphological changes and to quantify the density of gold labeling. RESULTS: DCX immunoreactivity was demonstrated within axon terminals, dendrites and somata in all groups. DCX and GABA or VGLUT1 were found to be co-localized in the axon terminals in all groups. We observed that DCX-immunoreactive (-ir) profiles formed synaptic contacts with GABAergic and glutamatergic terminals. The percentage of DCX labeling in dendrites, compared to axons, and the percentage of DCX-ir terminal profiles forming asymmetrical synapses, compared to those forming symmetrical synapses, were increased in all groups compared to the control group. DCX immunoreactivity in the 21-day-old GAERS group was found to be increased compared to the Wistar group. CONCLUSION: We conclude that newly born neurons are incorporated into the local hippocampal network in both the GAERS and the control Wistar rats. The results suggest that the neurogenesis taking place in the hippocampus may also be involved in the mechanism underlying absence seizures in GAERS.

Effect of Tacrolimus on Peripheral Nerve Regeneration in Allograft Transplantation: A Light and Electron Microscopic Study.

OBJECTIVES: Peripheral nerve injuries are common in Europe; however, the treatment techniques may lead to disabilities. This study aimed to evaluate the effect of tacrolimus use on the capacity of the epineural sheath graft to improve its regeneration quality in rat sciatic nerves as a treatment option for nerve injuries. MATERIALS AND METHODS: In the experimental process, 30 male Sprague Dawley were used as recipients and 10 Wistar rats were used as donors. Under anesthesia, all rats were operated on to resect the sciatic nerve. The nerve tissue of Wistar rats was used as allograft. In the autograft group, the resected nerve was reversed and sutured, resulting in an epineural sheath graft. For the allograft groups, rats were randomly divided into 2 groups as the tacrolimus-treated group and the nontreated group after allograft transplant. Tacrolimus was administered intramuscularly at 0.1 mg/kg daily for 12 weeks. After the treatment period, rats were killed and evaluated histomorphologically with light and electron microscopy. RESULTS: Histological examination showed no remarkable differences between different regions of the sciatic nerves (distal, middle, and proximal). The axonal density was decreased in the allograft groups compared with the autograft group (P < .001). Results showed that the number of mast cells was increased in the allograft group without tacrolimus treatment (P < .05). Similarly, there was a mild increase in mast cell count in the tacrolimus-treated allograft group. CONCLUSIONS: Our results showed that tacrolimus use in rats with implanted epineural nerve sheath supported recovery in terms of morphological and physiological regeneration of the nerve.

Astaxanthin alleviates oxidative damage in acute pancreatitis via direct antioxidant mechanisms.

BACKGROUND/AIMS: Astaxanthin (ATX) is a naturally occurring carotenoid and a potent antioxidant. Various anti-inflammatory effects of ATX have been examined. We aimed to investigate the protective effect of ATX and its mechanism in a cerulein-induced acute pancreatitis rat model. MATERIALS AND METHODS: The rats were randomized into 2 main groups as control (C) and acute pancreatitis group (AP). AP group was subsequently divided into subgroups as AP+vehicle (AP), AP+ATX, and ATX+peroxisome proliferator-activated receptor-alpha antagonist GW6471 (ATX+GW) groups. To induce AP, the rats were administered cerulein (50 µg/kg, intraperitonally [ip]) at 1 hour intervals, whereas the C group received saline. The AP group was treated with vehicle olive oil, ATX 40 mg/kg/orally, or GW6471 and ATX (GW1 mg/kg/ip; ATX; 40 mg/kg/peroral). Treatments were administered after the 1st cerulein injection. At the 7th hour after the final injection, the rats were killed and the pancreatic tissue was used for the determination of malondialdehyde (MDA), glutathione (GSH), and myeloperoxidase (MPO) activities and luminol-lucigenin chemiluminescence levels. Serum amylase, lipase, and histopathological analyses were performed. RESULTS: Elevated serum lipase and amylase levels in the vehicle-treated AP group (p<0.01) decreased in the ATX and ATX+GW groups (p<0.05). In the AP groups, GSH was reduced and MDA, MPO, luminol, and lucigenin levels were increased (p<0.05-0.001). ATX reversed these changes (p<0.05-0.001). The vehicle-treated group revealed significant severe cytoplasmic degeneration and vacuolization, whereas ATX ameliorated these destructions. GW6471 did not abolish the positive effects of ATX biochemically or histologically. CONCLUSION: ATX has a potent protective effect on AP via its radical scavenging and antioxidant properties. Therefore, we believe that ATX may have therapeutic potential.

Ultrastructural investigation of synaptic alterations in the rat hippocampus after irradiation and hyperthermia.

This study aimed to investigate ultrastructural synaptic alterations in rat hippocampus after in utero exposure to irradiation (IR) and postnatal exposure to hyperthermia (HT). There were four groups in each of the time points (3rd and 6th months). IR group: Pregnant rats were exposed to radiation on the 17th gestational day. HT group: Hyperthermia was applied to the rat pups on the 10th day after their birth. IR+HT group: Both IR and HT were applied at the same time periods. Control group: No IR or HT was applied. Rat pups were sacrificed after 3 and 6 months. Thin sections from the dentate gyrus (DG) and the CA3 of hippocampus were evaluated for synapse numbers by electron microscopy. Synapses were counted, and statistical analysis was performed. Abnormalities in myelin sheath, mossy terminals and neuropil were observed in the CA3 and DG of all groups. The synapses in the CA3 region were significantly increased in the IR-3rd month, IR-6th month, and IR+HT-3rd month groups vs control group. Synapses were significantly increased in the DG of HT-3rd month group. A trend for an increase in synapse numbers was seen in the CA3 and DG. Increased number of synapses in the rat hippocampus may be due to mossy fiber sprouting, possibly caused by in utero irradiation and/or postnatal hyperthermia.

The effect of topical and systemic tranexamic acid on fracture healing in rats.

OBJECTIVE: The aim of the present study was to determine the effect of topical and systemic tranexamic acid (TXA) on fracture healing in a rat surgical model. METHODS: We created standard, right-sided, open, diaphyseal femoral fractures with intramedullary Kirschner wire fixation in 48 male rats and divided them into three groups: a topical TXA (10 mg/kg) group, a systemic TXA (10 mg/kg) group, and a control group. Fracture healing was evaluated radiographically and histologically after early (week 2) and late (week 4) postoperative sacrifice. RESULTS: The radiological scores differed significantly among the all groups (p=0.001), as did the week 2 and 4 scores (p=0.003 and p=0.010, respectively). Radiologically, the topical TXA group exhibited better bone healing at both 2 (p=0.001) and 4 (p=0.007) weeks than the control group, and the systemic group showed better healing at both 2 (p=0.027) and 4 (p=0.023) weeks than the control TXA group. Moreover, bone healing was better in the group treated with topical rather than systemic TXA on radiological examinations performed at 2 (p=0.001) and 4 (p=0.007) weeks postoperatively (p=0.001 and p=0.007, respectively). Histologically, the groups differed significantly (p=0.001). The histological scores differed significantly among the all groups (p=0.001). At 2 weeks, the topical TXA group exhibited significantly better bone healing than the control group (p=0.001). CONCLUSION: Our results suggested that topical application of TXA in fracture patients may accelerate healing, whereas systemic administration may adversely affect healing.

Curcumin induces DNA damage by mediating homologous recombination mechanism in triple negative breast cancer.

Curcumin has a therapeutic potential activity through modulation of different signaling pathways in various types of cancer. However, the relationship between the efficacy of curcumin and the homologous recombination (HR) mechanism which plays important roles in the repair of double strand DNA (dsDNA) breaks remains uncertain. Herein, we explored curcumin-dependent dsDNA breaks and the association of curcumin with HR mechanism in triple negative breast cancer (TNBC). The cytotoxic and therapeutic activity of curcumin on HCC1937 (BRCA1 mutant), MDA-MB-231 (BRCA1 wild type) TNBC and HUVEC control cell lines were assessed. Then, the expression level and subcellular localization of H2AX, PARP1, BRCA1 and RAD51 were detected by RT-PCR and immunofluorescence analysis. Furthermore, ultrastructural changes of cell death were observed by TEM. Our findings for the first time demonstrated that curcumin's therapeutic activity was more pronounced in HCC1937 cells through the suppression of HR mechanism and the induction of dsDNA breaks. Consequently, curcumin based therapy could benefit in patients with TNBC particularly especially in women with a BRCA1 mutation.

Myrtus communis leaf extract protects against cerulein-induced acute pancreatitis in rats.

In this study, the aim was to examine the potential protective effects of Myrtus communis subsp. communis leaf ethanol extract (MC) treatment against acute pancreatitis (AP) in rats. Thirty-two rats were grouped as the saline-pretreated control (C), MC-pretreated control (MC), saline-pretreated AP (AP), and MC-pretreated AP (MC + AP) groups. To induce AP, cerulein was administered (50 µg/kg) two times. The rats were given MC for 14 days before cerulein injection. Six hours after the final cerulein injection, the rats were sacrificed. Pancreatic damage was associated with an increase in the serum activity of lipase and amylase, the pancreatic activity of myeloperoxidase, and the pancreatic level of malondialdehyde, interleukin-1ß, and interleukin-6. AP also led to a decrease in the pancreatic level of anti-inflammatory interleukin-10 and glutathione. Pretreatment with MC before the induction of AP significantly reduced the pancreatic damage observed during the histological examination as well as reversed the biochemical changes evoked by AP. PRACTICAL APPLICATIONS: Acute pancreatitis is characterized by high mortality (average about 5%; severe cases may reach about 30%). The current treatment for acute pancreatitis is mainly symptomatic. The introduction of herbal drugs may lead to the development of a new strategy in the treatment of this disease. This study revealed that MC reduced pancreatic injury by decreasing pro-inflammatory cytokines, increasing antioxidant capacity and anti-inflammatory cytokine, IL-10. To the authors' knowledge, this research is the first report showing that MC inhibits the development of AP. This observation suggests that MC may be useful in the prevention and the treatment of AP in clinical settings.

Melatonin supports alendronate in preserving bone matrix and prevents gastric inflammation in ovariectomized rats.

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.

Protective effects of different exercise modalities in an Alzheimer's disease-like model.

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 (100mg/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 (Aß), 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 Aß 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 Aß scores, and by improving antioxidant system and brain plasticity.