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Background and purpose: Chronic consumption of morphine (Mor) induces tolerance and dependence. This study aimed to survey the effects of pistachio extract (PX) on the induction and expression of Mor analgesic tolerance and physical dependency in mice. Experimental approach: Animals were randomly separated into six groups (n = 7): control, DMSO, Mor (10 mg/kg), Mor + saline, Mor + PX (10 mg/kg), and Mor + PX (100 mg/kg). Mor was injected (10 mg/kg, twice a day, s.c.) for 7 days to induce tolerance. PX was administered (10 and 100 mg/kg, orally) during the examination period. On each day and 20 min after Mor administration, a tail-flick test was done to measure the analgesic response and induction of tolerance. On day 7, naloxone (5 mg/kg, s.c.) was injected into the Mor-dependent animals to evaluate dependence, and animals were monitored for 30 min for jumping. Also, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were assessed in the brain tissue. Findings/Results: Our results indicated that co-administration of PX with Mor for 7 days diminished the induction of Mor tolerance. PX administration for 7 days alongside Mor reduced the frequency of withdrawal signs in naloxone-injected animals during dependence induction. Also, Mor increased the level of MDA and decreased the activities of SOD and GPx. Treatment with PX (100 mg/kg) restored all of the mentioned abnormalities. Conclusion and implications: According to the results presented in this study, chronic administration of PX forbade the induction of Mor analgesic tolerance and dependency in mice.

Abstract Chronic administration of d‐galactose (d‐gal) in rodents reproduces the overproduction of reactive oxygen species of physiological aging. The present research shows for the first time distinct signatures on d‐gal‐induced aging (500 mg/kg, 6 weeks) and the preventive and protective potential of two vitamin D (50 IU) supplementation regimens (pre‐induction and simultaneous, respectively) in two vital organs (heart and brain). d‐gal‐induced notorious alterations in working memory, a strong increase in brain malondialdehyde (MDA) oxidative levels, and strong downregulation of sirtuin 1 (SIRT1) in the heart and hippocampus and of calstabin2 in the heart. Cardiac and brain superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic antioxidant capacities were damaged, brain calstabin2 was downregulated, and neuropathology was observed. Heart damage also included a moderate increase in MDA levels, serologic lactate dehydrogenase (LDH), total creatine kinase (CK) activities, and histopathological alterations. The used dose of vitamin D was enough to prevent cognitive impairment, avoid muscular damage, hamper cardiac and cerebral oxidative stress, and SIRT1 and calstabin2 downregulation. Most importantly, the potencies of the two preventive schedules depended on the tissue and level of study. The pre‐induction schedule prevented d‐gal‐induced aging by 1 order of magnitude higher than simultaneous administration in all the variables studied except for SIRT1, whose strong downregulation induced by d‐gal was equally prevented by both schedules. The benefits of vitamin D for oxidative stress were stronger in the brain than in the heart. Brain MDA levels were more sensitive to damage, while SOD and GPx antioxidant enzymatic activities were in the heart. In this order, the magnitude of SOD, MDA, and GPx oxidative stress markers was sensitive to prevention. In summary, the results unveiled distinct aging induction, preventive signatures, and sensitivity of markers depending on different levels of study and tissues, which are relevant from a mechanistic view and in the design of targeted interventions.

Objective(s): Calcium dobesilate (CaD) has anti-oxidant, anti-inflammatory, and anti-apoptotic effects. In this study, the protective effects of CaD against hepatorenal damage induced by carbon tetrachloride (CCl4) in mice were evaluated. Materials and Methods: Thirty male mice were randomly divided into five groups: Control, CaD 100 mg/kg, CCl4, CCl4+CaD 50 mg/kg, and CCl4+CaD 100 mg/kg. CaD (50 and 100 mg/kg) was administered orally once a day for 4 weeks. The liver and kidney indices (serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase levels) were determined. Also, liver and kidney tissue oxidant/anti-oxidant markers (glutathione peroxidase, malondialdehyde, total anti-oxidant capacity, and superoxide dismutase) were measured. Cleaved caspase-3, Bax, cytochrome-c, and Bcl-2 protein levels were measured by immunoblotting method in the liver and kidney tissues. The liver and kidney histopathological changes were evaluated by the Hematoxylin and Eosin (H&E) staining method.Results: CCl4 induced significant oxidative stress and apoptosis in kidney and liver tissues that was concomitant with histopathological abnormalities in these organs in the CCl4 group versus the control (P

Objective(s): The Ischemia/reperfusion (I/R) phenomenon has a critical role in brain injuries induced by some kinds of stroke. The current study investigates the effects of Coenzyme Q10 (Q10) on global cerebral I/R in rats. Materials and Methods: Fifty male Wistar rats were used in this study. The global cerebral I/R was induced by obstructing both common carotid arteries for 20 min and the animals were treated with Q10 (200 mg/kg; PO.) for 6 weeks. Depressive and anxiety-like behaviors were assessed using the elevated plus-maze and forced swimming test, respectively. Working and spatial learning and memory were assessed by the Y-maze continuous alternation task and Morris water maze. The brain tissues were evaluated for brain edema, brain-derived neurotrophic factor (BDNF) levels, and superoxide dismutase (SOD) activities. Results: Our results indicated that global cerebral I/R increased anxiety and depression-like behavior as well as reduced cognitive performance. Moreover, the levels of BDNF and activities of SOD are reduced in stroke animals. Chronic post-stroke treatment with Q10 decreased brain edema. Furthermore, Q10 administration reduced anxiety and depressive-like behavior as well as cognitive impairments in stroke animals. Q10 also increased the SOD activities and BDNF levels in the brain tissues of stroke animals. Conclusion: Finally, we can conclude that using Q10 supplementation may be beneficial against the global cerebral I/R complications.

Objective(s): Delayed tissue plasminogen activator (tPA) thrombolysis is accompanied by different complications in stroke patients. Studies reported sex differences in stroke therapy. Ischemic postconditioning (PC) unveils neuroprotection in stroke models. In this study, we investigate the combined effect of delayed tPA therapy and PC procedure during an embolic stroke experimental model in female rats. Materials and Methods: Female Wistar rats were randomly divided into control (saline), tPA, PC, and tPA+PC groups after stroke induction via clot injection to the middle cerebral artery. tPA treatment was initiated 6 hr after stroke, and PC procedure was performed 6.5 hr post-ischemia induction (occlusion: 10 sec; reopening: 30 sec; 5 cycles). The cerebral blood flow (CBF) was recorded up to 60 min from IV tPA injection time. The parameters of brain edema, infarct volume, disruption of the blood-brain barrier (BBB), behavioral tests, and matrix metalloproteinases-9 (MMP-9) were evaluated.Results: This study revealed that PC conduction prevents excessive CBF increase by tPA and played a protective role in infarct volume reduction (P

Introduction: Memantine as N-Methyl-D-Aspartic Acid (NMDA) receptor antagonist is used in some neurological disorders. Moreover, memantine presents modulatory effects on the somatosensory information processing in healthy subjects. This study investigated the effects of memantine on electrophysiological properties of barrel cortex neurons in male rats. Methods: Single unit recording was used to evaluate the electrophysiological properties of barrel cortex neurons. The neural responses to the Principal Whisker (PW), Adjacent Whisker (AW), and combined displacement of two whiskers [20 ms Inter-Stimulus Intervals (ISIs)] were recorded before and 2 hours after memantine gavage (10 mg/kg). A Condition Test Ratio (CTR) was calculated for assessing inhibitory interactions. Results: Two hours after memantine gavage, neuronal ON and OFF responses to PW deflection were decreased. Furthermore, CTR for both ON and OFF responses was decreased following memantine administration. Conclusion: The current study demonstrated that memantine modified neural response properties in the rat barrel cortex.

Background and objectives: Cisplatin-induced nephrotoxicity accompanies increased oxidative stress, leading eventually to kidney dysfunction. On the other hand, Pistacia vera nuts (pistachio) display multiple pharmacological effects such as antioxidant property. The present study investigated the effects of pistachio hydroalcoholic extract on nephrotoxicity induced by cisplatin in mice. Methods: Pistachios (100 g) were powdered and macerated in 1 L of ethanol (80%) for 72 h Then, dried with rotary evaporator apparatus. Forty male mice were divided into five groups: normal, cisplatin, cisplatin+DMSO, cisplatin+ pistachio hydroalcoholic extract 10, and cisplatin+ pistachio hydroalcoholic extract 100. Nephrotoxicity was induced by intraperitoneal injection of cisplatin (20 mg/kg/day) on the first day of the experiment. Pistachio hydroalcoholic extract (10 and 100 mg/kg/p.o) was administered for four consecutive days. The body weight and kidney function indices such as serum creatinine (Cr) and blood urine nitrogen (BUN) were measured. Also, the renal tissues were assessed for levels of malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). Results: Cisplatin reduced animals’ body weight. Also, cisplatin increased levels of Cr, BUN, and MDA, and decreased the activities of SOD, CAT, and GPx. Treatment with pistachio hydroalcoholic extract (100 mg/kg) reduced the levels of serum Cr, BUN, as well as renal MDA. Moreover, administration of 100 mg/kg pistachio hydroalcoholic extract to cisplatin-treated mice increased the body weight as well as CAT, GPx, and SOD activities. Conclusion: These results imply that pistachio hydroalcoholic extract treatment may diminish cisplatin-induced renal dysfunction through reduction of oxidative stress in the kidney tissue.

Introduction: During menopause, which is a part of the aging process in women, the level of sex hormones decreases, which causes problems such as memory impairment and cognitive functions. One of the treatment options for these disorders is hormone therapy, which has several side effects. The present study investigated the effect of remote ischemic conditioning (RIC) technique on memory improvement, muscle strength, motor and balance function in ovariectomized rats. Methods: In the present experimental study, 24 Wistar female rats with an approximate weight of (170-220 g) were divided into three groups (n = 8) including, 1: control group, 2: ovariectomy group and 3: ovariectomy+ treatment group. Initially, the animals in the second and third groups underwent ovariectomy surgery. The RIC techniques were performed on treatment group of rats for two months. After that, memory, muscle strength, and motor and balance function were assessed in all groups. SPSS software (V21) and one-way analysis of variance were used for statistical analysis. Results: The result of this study showed that RIC technique significantly improved memory in the ovariectomy+treatment group in comparison with the ovariectomy group (P

Background and purpose: Opiates are traditionally used for the treatment of pain. Chronic consumption of opiates such as morphine (MOR) induces tolerance and dependence. This study aimed to investigate the effects of valsartan (VAL), as an angiotensin II receptor blocker, on the induction and expression of MOR analgesic tolerance and physical dependence in rats. Experimental approach: MOR 10 mg/kg was injected s.c. twice a day for 7 days to induce tolerance and dependence. For evaluating the effect of VAL on the induction of MOR analgesic tolerance and physical dependence, 20 mg/kg VAL was administered orally (once a day) during the 7 days of the examination period. The tail-flick test was performed every day. On day 7, 5 mg/kg naloxone () was injected s.c. into the morphine-dependent rats and the rats were monitored for 30 min for the frequency of withdrawal signs such as jumping, diarrhea, defecation, head tremor, rearing, scratching, sniffing, teeth chattering, and wet-dog shake. For evaluating the effect of VAL on the expression of MOR-analgesic tolerance and physical dependence, 45 min before the last MOR injection, VAL was administered only on day 7. The tail-flick test was performed and naloxone was injected into the addicted rats and they were monitored for 30 min for the frequency of withdrawal signs such as jumping, diarrhea, defecation, head tremor, rearing, scratching, sniffing, teeth chattering, and wet-dog shake. Findings/Results: Our results revealed that the co-administration of VAL with MOR for 7 consecutive days reduced the induction of MOR tolerance. Moreover, VAL administration for 7 days along with MOR reduced the frequency of diarrhea and defecation in naloxone-injected animals. Conclusion and implications: According to the results presented in this study, chronic administration of VAL prevented the induction of MOR-analgesic tolerance and dependence in rats.

Unilateral ureteral obstruction (UUO) as a clinical disorder can cause renal damage. The permanent injury occurs if the obstruction is not relieved. Renal injury can be reversed with UUO removal (RUUO). RUUO attenuates the renal hemodynamic and functional impairment and decreases the renal fibrosis and apoptosis. Nevertheless, kidney injury may continue after RUUO, and synchronous medication therapy seems necessary. However, UUO and post-RUUO periods are also important in final renal recovery. To date, various therapeutic strategies have been applied to develop renal recoverability after RUUO. In animal studies, the effect of some pharmacological agents such as mesenchymal stem cells, anti-inflammation drugs, L-arginine, bone morphogenetic protein-7, epidermal growth factor, allopurinol, renin-angiotensin system antagonists, and endothelin A/B receptor blocker were surveyed in RUUO model. Also, post-RUUO renal recoverability has been studied in human researches. In these studies, the effective strategies have focused on surgery for RUUO creation via urethrotomy, urethroplasty, stent balloon dilatation, and stenting. Accordingly, in this review, we focused on the therapeutic procedure of renal recovery after the RUUO situation in human and animal studies.

Introduction: Aging is a complex process and is considered as a risk factor for many diseases such as hypertension, Alzheimer, cancer, depression and anxiety. Recently, it has been shown that metformin, an anti-diabetic drug, has important neurological effects such as preventing memory loss, stroke, anxiety, inflammation and seizures. Therefore, the aim of this study was investigating the effects of metformin on some cognitive factors in elderly male rats. Methods: 24 rats (22 months) were randomly divided into 3 groups (n=8). The first group was the control group that received water orally, the second group received metformin 1 mg/kg orally and the third group received metformin 10 mg/kg orally. After treatment for 40 days (once daily), behavioral tests, including Y-maze, elevated plus maze and depression test were performed on animals. Results were analyzed using GraphPad Prism version 6 and One-way ANOVA followed by Tukey-post hoc test. Results: The results of this study showed that metformin at a dose of 10 mg/kg significantly reduced anxiety (P

Objective(s): Ceftriaxone (Cef), a beta-lactam antibiotic, is accompanied by antioxidant and anti-inflammatory properties. It has been shown that Cef has beneficial effects on Alzheimer’s disease. In the current investigation, the effect of Cef in a mice model of aging was investigated. Materials and Methods: Forty male mice were equally aliquoted into four groups as follows: Control (as healthy normal animals), D-galactose (DG) group (treated with 500 mg/kg/day DG for 6 weeks), DG + Cef group (treated with DG plus Cef 200 mg/kg/day for 6 weeks), and Cef group (treated with Cef 200 mg/kg/day for 6 weeks). A battery of behavioral tests was done to evaluate age-related neurocognitive changes. The activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), as well as the level of malondialdehyde (MDA) in the brain, were measured by biochemical methods. Also, to determine the brain damage, histopathological alterations in the hippocampus were measured using hematoxylin and eosin (H&E) staining. Results: Our results indicate that neurobehavioral dysfunctions of DG can be prevented by co-administration of Cef. We also found that Cef increases the activity of SOD, GPx, and CAT as well as decreasing the level of MDA in the brain of aged mice. Conclusion: Based on our findings, Cef declines neurocognitive dysfunctions in the DG-induced model of aging, possibly through its antioxidative properties.

Background and purpose: Natural products are used to improve the damage caused by harmful reagents in various pathological situations. This study investigated the effect of grape sap as a natural product with antioxidant properties on follicle cell proliferation in bleomycin (as a chemotherapy agent with toxic effects on hair growth) treated rats skin. Experimental approach: The bleomycin treated rats were administrated grape sap. Wingless/integrated (wnt) and β-catenin gene expression as follicle proliferative markers were evaluated using real-time polymerase chain reaction. Furthermore, histological factors and total antioxidant capacity were evaluated. Findings / Results: The data showed that, grape sap increased the number of anagenic hair follicle in grape sap (100 mg/kg) group (P < 0.001), sebaceous glands (P < 0.001), blood vessel density (P < 0.001), and hair growth length (P < 0.001). Also, wnt and β-catenin gene expression was elevated. The data showed that wnt and β-catenin gene expression were elevated in grape sap treated animals versus bleomycin group (P < 0.01 and 0.001, respectively). Conclusion and implications: Our finding showed that grape sap can be effective in increasing hair growth a gains bleomycin toxic effects on skin hair growth.

Objective(s): This study investigated the role of locus coeruleus (LC) nucleus TRPV1 receptors (TRPV1r) in the expression and development of morphine physical dependence by intra-LC administration of AMG9810 (selective TRPV1r antagonist) in male Wistar rats. Materials and Methods: For assessing the development of morphine dependence, AMG9810 (0.03 and 0.3 mM in 10% DMSO, 0.2 µl; intra-LC microinjection) was administered before each morphine administration for seven continues days (once daily; 6, 16, 26, 36, 46, 56, and 66 mg/kg; sc). Furthermore, for evaluating the expression of morphine dependence, a single dose of AMG9810 (0.03 and 0.3 mM in 10% DMSO, 0.2 µl; intra-LC microinjection) was administered to morphine-dependent rats on day 8 of the experiment. Results: Obtained data demonstrated that co-administration of TRPV1r antagonist with morphine reduced the development of morphine withdrawal syndrome somatic signs induced by naloxone. Moreover, single intra-LC administration of TRPV1r antagonist on the final day of the examination period significantly decreased the expression of some signs of morphine withdrawal in rats. Conclusion: The results showed that LC TRPV1r might be participating in the expression and development of morphine dependence.

Background and objectives: Menopause is associated with depression as well as emotional and memory disorders. Based on the anti-inflammatory and antioxidant effects of pistachio, its effect on depression, cognitive function, anxiety and physical power in ovariectomized mice was investigated. Methods: In the current study, fifty female mice were used. They were aliquoted into five groups: control, ovariectomy (OVX), ovariectomy + DMSO, ovariectomy +10 mg/kg pistachioextract and Ovariectomy +100 mg/kg pistachio extract. In order to prepare the required extract, pistachio nuts were powdered (100 g) and macerated in 1 L of ethanol (80%) for 72 h. Pistachio extract was used orally once a day in ovariectomized mice for sixty days. Anxiety, depression, working memory and physical power were evaluated by the Elevated plus-maze (EPM) test, Forced swimming test (FST), Y maze and swimming exhaustion test, respectively. Results: The results showed that extract of pistachio (more potentially at the dose of 100 mg/kg) decreased anxiety-like behaviors and depression; besides, increase in working memory and physical power was observed in the ovariectomized mice. Conclusion: The findings of the current investigation suggest that pistachio extract could be used as a potential strategy for the attenuation of ovariectomy-related manifestation

Objective(s): Cisplatin (Cis) is an anticancer compound, which is used for the treatment of various cancers. Sumatriptan (Suma) is a selective agonist of 5-hydroxytryptamine 1B/1D (5HT1B/1D) receptor, which is prescribed for the management of migraine. It is well-established that Suma has anti-inflammatory and antioxidant properties. We have explored the protective effects of Suma in the mitigation of Cis-induced nephrotoxicity. Materials and Methods: The mice received a single IP injection of Cis (20 mg/kg) on the first day of the experiment. Suma treatment (0.1 and 0.3 mg/kg/day, IP) was started on day 1 and continued for 3 consecutive days. Results: Creatinine (Cr), blood urea nitrogen (BUN) and malondialdehyde (MDA) levels were elevated and glutathione peroxidase (GPx) as well as superoxide dismutase (SOD) activities were decreased in Cis-treated mice. Suma (more potently 0.3 mg/kg) reduced Cr, BUN and MDA levels and increased SOD and GPx levels. Suma also reduced the acute renal injury (tubular degeneration, tubular cells vacuolation, tubular necrosis and cast), which corresponded to kidney damage in Cis-treated mice. Conclusion: These findings demonstrate that Suma mitigates Cis-induced renal injury by inhibition of oxidative stress and enhancing the antioxidant enzymes activities.

Objective (s): Silver nanoparticles (NPs) have attracted considerable attention owing to their important properties, including antimicrobial and anti-oxidative stress effects. However, high concentrations of silver NPs have been reported to have toxic effects. The present study aimed to evaluate the modulatory and protective effects of royal jelly (RJ) against the harmful effects of silver NPs on hippocampal functions, such as learning and memory. Materials and Methods: This experimental study was conducted on 40 male Wistar rats. The animals were divided into four groups of 10, including the control group (no silver NPs and RJ), RJ group, silver NPs plus RJ, and silver NPs. Some functions of the hippocampus (e.g., learning and memory) were evaluated using Morris memory function tests for four consecutive days. In addition, the relative expression of TRPV1 was assessed using real-time polymerase chain reaction (RT-PCR). At the final stage, hippocampal tissues were collected for histological studies.Results: Levels of learning and memory, relative gene expression ratio of TRPV1, and the histological changes in the hippocampus were significantly different in the groups receiving silver NPs compared to the groups administered with RJ. Conclusion: According to the results, RJ may be the effective in the protection against the adverse effects of silver NPs and improve the function of the hippocampus.

Objective(s): Growing evidence suggests that dysfunction of the glutamatergic system and α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptors are involved in pathology of Alzheimer’s disease (AD). Because AMPA receptors play a key role in plasticity synaptic regulation, positive modulation of these receptors may rescue the cognitive deficits in the AD. The aim of this study was to explore the effect of CX691, a specific positive allosteric modulator of the AMPA-type glutamate receptors (Ampakine), on spatial learning and memory in a rat model of AD. Materials and Methods: For induction of AD, amyloid-beta 1-42 (Aβ1-42) was microinjected into the hippocampus of male Wistar rats (250-300 g). The Morris water maze (MWM) test was used to evaluate the effect of CX691 (0.03 and 0.3 mg/kg, twice a day for 10 days, orally) on spatial learning and memory of rats. In order to evaluate the protein expression of brain-derived neurotrophic factor (BDNF) in hippocampus tissue, ELISA test was used. Results: The obtained data showed that treatment with CX691 (0.3 mg/kg) improves the impairment of spatial learning and memory in AD rats. Also, treatment with CX691 (0.3 mg/kg), increased the BDNF protein level in hippocampus tissue of AD rats compared to non-treated animals.Conclusion: The CX691 can improve the BDNF protein expression as well as spatial performance of learning and memory in AD rats.

Opiate tolerance and dependence is a worldwide public health problem and gives a significant burden to society. The aim of this study was to evaluate the effects of metformin (MET) on development and expression of morphine tolerance and dependence in rats. For induction of tolerance, morphine sulfate was injected (10 mg/kg, twice a day, s.c.) for 7 days. Animals received metformin (5 and 50 mg/kg, orally, daily) during the examination period for assessing the development of morphine tolerance and dependence. In order to evaluate the expression of morphine tolerance and dependence, single doses of MET (5 and 50 mg/kg, orally) were administered on day 7. Tail flick test was performed to assess the induction of morphine tolerance. For evaluation of morphine dependence, naloxone-induced jumping (5 mg/kg, s.c.) was monitored. Our results showed that 7 days coadministration of 50 mg/kg of MET significantly reduced the development of morphine analgesic tolerance versus morphine + saline treated rats (P < 0.001). Treatment with 50 mg/kg MET reduced the incidence and frequency of jumping in naloxone injected animals (P < 0.01). It is notable that single dose administration of MET, did not prevent the expression of analgesic tolerance and physical dependence to morphine. Based on these results, it can be concluded that MET attenuates the development of morphine analgesic tolerance and dependence in rats.

Objective(s): Metformin (Met), an antidiabetic biguanide, reduces hyperglycemia via improving glucose utilization and reducing the gluconeogenesis. Met has been shown to exert neuroprotective, antioxidant and anti-inflammatory properties. The present study investigated the possible effect of Met on the D-galactose (D-gal)-induced aging in mice. Materials and Methods: Met (1 and 10 mg/kg/p.o.), was administrated daily in D-gal-received (500 mg/kg/p.o.) mice model of aging for six weeks. Anxiety-like behavior, cognitive function, and physical power were evaluated by the elevated plus-maze, novel object recognition task (NORT), and forced swimming capacity test, respectively. The brains were analyzed for the level of superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF). Results: Met decreased the anxiety-like behavior in D-gal-treated mice. Also, Met treated mice showed significantly improved learning and memory ability in NORT compared to the D-gal-treated mice. Furthermore, Met increased the physical power as well as the activity of SOD and BDNF level in D-gal-treated mice. Conclusion: Our results suggest that the use of Met can be an effective strategy for prevention and treatment of D-gal-induced aging in animal models. This effect seems to be mediated by attenuation of oxidative stress and enhancement of the neurotrophic factors.

Objective: To investigate the effect of crocin carotenoid on BNDF and CREB gene expression in the brain ventral tegmental area (VTA) and the serum level of BDNF in morphine-treated rats compared to control. Methods: In this study, 40 male Wistar rats (200-250 g) were used in 5 experimental groups: 1) non morphine treat rats (control); 2) non morphine-treated rats with 25 mg/kg crocin carotenoid (i.p., for 21 d); 3) morphine treated rats (10 mg/kg twice a day, s.c., 21 d); 4 and 5) morphine-treated rats with 12.5 and 25 mg/kg crocin carotenoid, respectively. By the end of research, BDNF and CREB expression was determined by real-time-PCR method. ELISA analysis was also applied for assessing the serum BDNF level. Results: The data indicated that morphine treatment could cause a significant decrease in BDNF and CREB gene expression (P

The long-term treatment of mice with D-galactose (D-gal) induces the overproduction of reactive oxygen species (ROS) and is a well-accepted experimental model of oxidative stress-linked cognitive disorders in physiological aging. Calcium dobesilate (CaD, Doxium®) is an established vasoactive and angioprotective drug commonly used for the clinical treatment of diabetic retinopathy and chronic venous insufficiency. It has antioxidant properties and controls vascular permeability. In the current study, we evaluated the protective effects of CaD (50 and 100 mg/kg/day p.o.) in male mice treated with D-gal (500 mg/kg/day p.o.) for six weeks. Results demonstrated that body weight loss, anxiety-like and cognitive impairments of D-gal-treated animals were reversed by CaD administration as evaluated by the measurement of mice performance in elevated plus-maze, Y-maze, and shuttle box tests. CaD treatment also inhibited the oxidative stress in aging mouse brains by decreasing malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) enzyme activities. These results could open new perspectives for the clinical use of CaD in treating and preventing cognitive impairment in older people.

Background and Aim: Diabetes mellitus and continued hyperglycemic condition prompt serious diabetic complications such as diabetic neuropathy. Numerous studies have shown the involvement of oxidative stress and high glucose-induced cell death in the progress of diabetic neuropathy. Rosmarinus officinalis L has been suggested in the literature as an anti-diabetic herbal medicine that contains potent antioxidant components. Therefore, the neuroprotective effect of Rosmarinus officinalis L (RE) extract was investigated in glucose-induced neurotoxicity via pheochromocytoma )PC12( cells as an appropriate in vitro model of diabetic neuropathy. Materials and Methods: Cell viability was determined using MTT assay. Cleave caspase-3 and Bax: Bcl2 ratio, as biochemical parameters of cellular apoptosis, were measured by western blotting analysis. Results: Our data showed that a 4-fold elevation in the medium glucose significantly reduced cell viability (P < 0.01) and increased caspase-3 activation (P < 0.01) as well as Bax: Bcl2 ratio (P < 0.05) in PC12 cells after 24 h. Incubation of high glucose medium cells with 60μg/ml RE extract decreased high glucose-induced cell toxicity and prevented caspase-3 activation and Bax: Bcl2 ratio. Conclusion: It could be concluded that RE extract is effective in the protection against hyperglycemia-induced cellular toxicity. This could be relevant to the prevention of apoptosis. Moreover, the results suggest that RE has the therapeutic potential to attenuate diabetes complications such as that neuropathy.

Background and Aim:The protective effect of oleuropein,a chief polyphenol compound in olive tree, on cisplatin-induced nephrotoxicity in human cultured renal tubular cells, GP-293, was investigated. Materials and Methods:Cell viability was determined by the MTT assay. Cleaved caspase-3 and Bax: Bcl2 ratioas biochemical parameters of cellular apoptosis, was assessed using western blot analysis. Results:Our data showed that cisplatin in the dose of 55µg/ml significantly can reduced cell viability, increased caspase-3 activation and Bax: Bcl2 ratio in GP-293 cells after 24hr. Incubation of the cisplatin treated cells, with 20μg/ml oleuropein decreased the cisplatin-induced cell toxicity, as well as prevented caspase-3 activation and reduced Bax: Bcl2 elevation ratio. Conclusions: Oleuropein protects against cisplatin-induced cellular toxicity. This could be associated with the prevention of cellular apoptosis

Studies have shown that following opiate withdrawal, the spontaneous discharge rate of locus coeruleus (LC) neurons remarkably increases. Combination of intrinsic mechanisms with extrinsic excitatory modulations mediates the withdrawal-induced hyperactivity of LC neurons. The nucleus paragigantocellularis (PGi) provides the main excitatory inputs to LC and plays a pivotal role in opiate withdrawal. In the present study the direct facilitatory role of PGi on opiate withdrawal-induced hyperactivity of LC neurons was investigated using a newly developed brain slice, containing both LC and PGi. HRP retrograde neuronal tracing was used to verify the existence of both LC and PGi neurons in the developed slice. The spontaneous discharge rate (SDR), resting membrane potential (RMP) and spontaneous excitatory post-synaptic currents (sEPSCs) were recorded in LC neurons using whole cell patch clamp recording. Results showed that the net SDR and the net RMP of LC neurons in slices containing both LC and PGi neurons are significantly higher than slices lacking intact (uncut) PGi inputs. Also, the frequency of sEPSCs in those LC neurons receiving PGi inputs significantly increased compared to the slices containing no intact PGi inputs. Altogether, our results propose that increase in PGi-mediated excitatory transmission might facilitate the opiate withdrawal-induced hyperactivity of LC neurons.