Oral administration of coenzyme Q10 ameliorates memory impairment induced by nicotine-ethanol abstinence through restoration of biochemical changes in male rat hippocampal tissues.

Substance abuse among adolescents has become a growing issue throughout the world. The significance of research on this life period is based on the occurrence of neurobiological changes in adolescent brain which makes the individual more susceptible for risk-taking and impulsive behaviors. Alcohol and nicotine are among the most available drugs of abuse in adolescents. Prolonged consumption of nicotine and alcohol leads to drug dependence and withdrawal which induce various dysfunctions such as memory loss. Coenzyme Q10 (CoQ10) is known to improve learning and memory deficits induced by various pathological conditions such as Diabetes mellitus and Alzheimer's disease. In the present study we investigated whether CoQ10 treatment ameliorates memory loss following a nicotine-ethanol abstinence. Morris water maze and novel object recognition tests were done in male Wistar rats undergone nicotine-ethanol abstinence and the effect of CoQ10 was assessed on at behavioral and biochemical levels. Results indicated that nicotine-ethanol abstinence induces memory dysfunction which is associated with increased oxidative and inflammatory response, reduced cholinergic and neurotrophic function plus elevated Amyloid-B levels in hippocampi. CoQ10 treatment prevented memory deficits and biochemical alterations. Interestingly, this ameliorative effect of CoQ10 was found to be dose-dependent in most experiments and almost equipotential to that of bupropion and naloxone co-administration. CoQ10 treatment could effectively improve memory defects induced by nicotine-ethanol consumption through attenuation of oxidative damage, inflammation, amyloid-B level and enhancement of cholinergic and neurotrophic drive. Further studies are required to assess the unknown side effects and high dose tolerability of the drug in human subjects.

Neuro-protective Effect of Acetyl-11-keto-ß-boswellic Acid in a Rat Model of Scopolamine-induced Cholinergic Dysfunction.

BACKGROUND: Acetyl-11-keto-ß-boswellic acid (AKBA) is a major component of the oleo-gum resin of B. serrata with multiple pharmacological activities. The objective of this study was to explore the underlying mechanisms of neuroprotective potential of AKBA against scopolamine-mediated cholinergic dysfunction and memory deficits in rats. METHODS: The rats received AKBA (2.5, 5, and 10 mg/kg, oral) for 21 days. In the third week, scopolamine was administered 30 min before the Morris water maze and passive avoidance tests. In order to perform biochemical assessments, the hippocampus and prefrontal cortex were extracted from the rats euthanized under deep anesthesia. RESULTS: In the MWM test, treatment with AKBA (5 and 10 mg/kg) decreased the latency and distance to find the platform. Moreover, in the PA test, AKBA remarkably increased latency to darkness and stayed time in lightness while decreasing the frequency of entry and time in the darkness. According to the biochemical assessments, AKBA decreased acetylcholinesterase activity and malondialdehyde levels while increasing antioxidant enzymes and total thiol content. Furthermore, AKBA administration restored the hippocampal mRNA and protein levels of brain-derived neurotrophic factor (BDNF) and mRNA expression of B-cell lymphoma (Bcl)- 2 and Bcl-2- associated X genes in brain tissue of scopolamine-injured rats. CONCLUSION: The results suggested the effectiveness of AKBA in preventing learning and memory dysfunction induced by scopolamine. Accordingly, these protective effects might be produced by modulating BDNF, cholinergic system function, oxidative stress, and apoptotic markers.

Assessment of the neuroprotective effect of Cocos nucifera L. oil on learning and behavior impairment in ovariectomized rats.

Objective: The current study aimed to investigate whether Cocos nucifera L. oil (CO) is effective on menopause-related memory dysfunction in ovariectomized (OVX) rats. Materials and Methods: Fifty healthy female Wistar rats were randomly selected and classified into five groups as control, OVX rats, and three OVX groups of rats which received three different doses (100, 200, and 400 mg/kg/day) of CO for five consecutive weeks by gavage. To assess the effect of CO, neurobehavioral tests such as Morris water maze (MWM) and Passive avoidance (PA) were done and then the animals were sacrificed to remove cortical and hippocampal tissues for biochemical analysis. Results: In both behavioral tests including MWM and PA, treatment with CO particularly two higher doses of 200, and 400 mg/kg demonstrated significant improvement in comparison with OVX group. Furthermore, antioxidant biomarkers such as total thiol content, catalase and superoxide dismutase (SOD) activities were significantly higher in the OVX-CO groups versus the OVX group. On the contrary, malondialdehyde (MDA) concentration as an oxidative stress biomarker was remarkably lower in the OVX-CO200 and 400 mg groups than the OVX group. Conclusion: The present study demonstrated the significant improvement of CO on learning and memory impairment induced by ovariectomy. Although the exact mechanism needs further investigation, it might have occurred due to the anti-oxidative effect of CO.

Folic acid ameliorates anxiety and depressive like behavior induced by nicotine withdrawal through restoration of behavioral and biochemical alterations in adolescent male rats.

INTRODUCTION: The present study aimed to assess the efficacy of folic acid (FA) on withdrawal following nicotine (Nic) administration in adolescent male rats. METHODS: Adolescent male rats were divided into two groups: 1) vehicle and 2)Nic (Nic-2mg/kg), and were under the treatment from 21 to 42 days of age. After that, they continued the experiment without treatment and returned to a regular diet, except for one of those who received Nic. The rats were divided into four groups where they were treated with different doses of FA (5, 10, and 15 mg/kg) and bupropion (Bup) by oral gavage, and the final group included normal rats that received only FA (15mg/kg) from 42 days of age for three weeks during which withdrawal occurred. RESULTS: Results showed that adolescent Nic exposure exacerbated the behavioral indices of anxiety- and depression-like behaviors, while FA attenuated the effects of Nic withdrawal on anxiety and depression as well as Bup. In support, the biochemical results demonstrated a balance between oxidant and antioxidant mediators in addition to increase and decrease of serotonin and monoamine oxidase (MAO) activity in cortical tissue. TNF-α as an inflammatory agent was decreased, whereas IL-10 as an anti-inflammatory parameter was increased. CONCLUSION: The present findings suggest anxiety and depression caused by Nic withdrawal were attenuated by FA more likely through reduction activity of MAO, the important enzyme responsible for serotonin metabolism along with balance between oxidant/anti-oxidant and pro-inflammatory/anti-inflammatory mediators. However, various mechanisms might be involved, which requires further investigation. IMPLICATIONS: Nic withdrawal induced depression and anxiety like behavior in rats followed by neuro-oxidative damage and neuro-inflammation. Folic acid supplementation as well as bupropion improved cognitive disorders induced by Nic withdrawal by increasing neuro-inflammation, neuro-oxidative damage.

Omega-3 fatty acids prevent nicotine withdrawal-induced impairment of learning and memory via affecting oxidative status, inflammatory response, cholinergic activity, BDNF and amyloid-B in rat hippocampal tissues.

In the present study, the main objective was to reveal whether treatment by Omega-3 fatty acids could prevent the adverse effects of adolescent nicotine withdrawal on spatial and avoidance memory in male rats. For this purpose, Morris water maze and passive avoidance tests were performed on male Wistar rats and the hippocampal levels of oxidative stress markers, inflammatory indices, brain-derived neurotrophic factor, nitrite, amyloid-B and acetylcholinesterase (AChE) were measured. Moreover, density of dark neurons were assessed in CA1 and CA3 regions. Results showed that adolescent nicotine exposure followed by a period of drug cessation exacerbates the behavioral indices of learning and memory through affecting a variety of biochemical markers within the hippocampal tissues. These changes lead to elevation of oxidative and inflammatory markers, reduction of neurotrophic capacity and increased AChE activity in hippocampal tissues. In addition, it was observed that co-administration of nicotine with Omega-3 fatty acids significantly prevents nicotine withdrawal-induced adverse effects through restoration of the mentioned biochemical disturbances. Therefore, we suggest administration of Omega-3 fatty acids as a safe, inexpensive and effective therapeutic strategy for prevention of memory dysfunctions associated with nicotine abstinence during adolescence.

Vitamin B12 reversed anxiety and depression induced by adolescent nicotine withdrawal through alteration the inflammatory, oxidative and serotoninergic profiles in male rats.

BACKGROUND: The present study aims to assess the effect of vitamin B12 (Vit B12) on depression-like behavior caused by nicotine (Nic) withdrawal, which is more likely due to the anxiogenic effect of Nic in adolescent male rats, through assessing behavioral and biochemical analysis. METHODS: Adolescent male rats were divided into vehicle (received normal saline), and experimental groups that received Nic (2 mg/kg, intraperitoneally (i.p.)) for three consecutive weeks and after that, the group that received normal saline was divided into two groups, one of which returned to a regular diet, and the second one received Vit B12 (1.5 mg/kg). The Nic group was divided into five groups, one of which received bupropion (Bup, 20 mg/kg), three of which received different doses of Vit B12 (0.5, 1, and 1.5 mg/kg), and the last one returned to a normal diet without treatment, which was considered as the withdrawal period. RESULTS: Behavioral analysis showed that Nic withdrawal induced anxiety and depression. Vit B12 and Bup reduced anxiety and depression induced by Nic withdrawal. The biochemical analysis demonstrated the more activity of oxidative stress factors and pro-inflammatory cytokines in which Nic was administered, whereas both Vit B12 and Bup reversed the results and improved the activity of both antioxidant and anti-inflammatory parameters. Furthermore, both serum and cortical Vit B12 levels dramatically decreased in nicotine group, whereas treatment with both Vit B12 and Bup as desirable treatments corrected Vit B12 levels. CONCLUSION: According to the present findings, the results revealed that Vit B12 is comparable with Bup in attenuation of Nic withdrawal symptoms. In addition, both Bup and Vit B12 improved the decreased serum and cortical levels of Vit B12, which caused by nicotine. Administration of Vit B12 in normal animals demonstrated better results in reducing antioxidant and anti-inflammatory parameters, which explores new hope to introduce Vit B12 as a novel antioxidant and anti-inflammatory agent to treat not only withdrawal, but also other diseases related to the prominent role of oxidative stress or inflammatory pathways, such as Alzheimer's disease.

Capparis spinosa Promoted BDNF and Antioxidant Enzyme Levels to Protect Against Learning and Memory Deficits Induced by Scopolamine.

BACKGROUND: Alzheimer's disease (AD) is a major neurodegenerative disorder with multiple manifestations, including oxidative stress, brain-derived neurotrophic factor (BDNF) depletion, and cholinergic dysfunction. Capparis spinosa (C. spinosa) is identified as a potential source of nutrition for alleviating various ailments. The current study assessed the ameliorating properties of C. spinosa hydroethanolic extract on memory dysfunction and the possible roles of oxidative stress and BDNF in the scopolamine (Scop)-treated rats. METHODS: Forty male Wistar rats were divided into the following four groups: Control, Scop (2 mg/kg, intraperitoneal injection (i.p.)), Scop + C. spinosa 150, and Scop + C. spinosa 300 groups. The rats were given C. spinosa extract (150 or 300 mg/kg, oral) for 3 weeks. During the third week, Passive Avoidance (PA) and Morris Water Maze (MWM) tests were done to assess memory and learning performance. Finally, oxidative stress markers and BDNF in the brain tissue were evaluated. RESULTS: Scop injection was associated with a significant increase in the time latency and travelled distance to reach the platform during the learning phase of MWM In the probe test, the Scoptreated rats showed a lower time and distance in the target area. Furthermore, Scop injection significantly decreased the latency to enter the dark while increasing the dark time and the frequency of entries to the dark zone of the PA task. C. spinosa extract effectively reversed the behavioural changes induced by Scop. Treatment with the extract also significantly increased the levels of superoxide dismutase, catalase, thiols, and BDNF, while decreasing malondialdehyde production in the brains of the Scop-injured rats. CONCLUSION: C. spinosa hydroethanolic extract successfully ameliorated Scop-induced memory impairment by modifying BDNF and oxidative stress markers in the brain of amnesic rats.

Rosiglitazone attenuates amyloid beta and glial fibrillary acidic protein in the hippocampus and neuroinflammation associated learning and memory impairments in rats.

OBJECTIVE: The aim of the current study was to investigate the beneficial effects of rosiglitazone (Rosi) on amyloid beta(Aß) and glial fibrillary acidic protein (GFAP) in the hippocampus and neuroinflammation-associated learning and memory impairments in rats. MATERIALS AND METHODS: The rats were grouped and treated as follows: (1) Control in which saline and vehicle were administered instead of LPS and Rosi respectively. (2) Lipopolysaccharide (LPS) group in which LPS was dissolved in saline and injected (1 mg/kg) intraperitoneally. Vehicle was administered instead of Rosi in this group. (3-5) LPS+ Rosi 1, LPS+ Rosi 3, and LPS+ Rosi 5 groups in them 1, 3, or 5 mg/kg of Rosi respectively was administered 30 min before LPS. The treatments were done for two weeks. In the first week, Rosi or its vehicle was injected 30 min before LPS. In the second week, the treatments were the same as the first week and behavioral tests were also carried out in the second week. The hippocampal tissues were finally detached for biochemical assessment. RESULTS: The results showed that Rosi reversed increased levels of Aß, GFAP, interleukin (IL)- 6, tumor necrosis factor-α (TNF-α), nitric oxide (NO) metabolites, and malondialdehyde (MDA) due to LPS injection. Rosi also reversed attenuating effects of LPS on IL-10 and thiol concentration and activities of catalase (CAT) and superoxide dismutase (SOD). In the Morris water maze test, the LPS group had a longer latency to find the platform while spent a shorter time spent in the target quadrant in the probe trial than the control group. In the passive avoidance test, the animals of the LPS group had a shorter delay to enter the dark chamber than the animals of the control group. Treatment with Rosi reversed these parameters. CONCLUSION: The findings showed Rosi attenuated Aß, GFAP, and oxidative stress in the hippocampus and neuroinflammation-associated learning and memory impairments in rats.

Memantine, an NMDA receptor antagonist, protected the brain against the long-term consequences of sepsis in mice.

AIMS: Long-term neuroinflammation and brain dysfunction have frequently been reported in sepsis survivors. In this study, the protective effect of memantine (an NMDA receptor antagonist) on the long-term consequences of sepsis on the brain was investigated in mice. MATERIALS AND METHODS: Eighty-five male C57 mice were included. Memantine was administrated through gavage at 5, 10, and 20 mg/kg three days before sepsis and continued for three days after sepsis induction. Sepsis was induced by intraperitoneal injection of 5 mg/kg LPS. A cohort of mice was sacrificed on the 4th day post sepsis to measure NF-κB, TNF-α, and IL-1ß mRNA expression and oxidative stress markers in the brain. The second cohort was used for behavioral tests one month after sepsis induction and then sacrificed for oxidative stress markers and acetylcholinesterase (AChE) activity measurement. KEY FINDINGS: MDA levels and mRNA expression of NF-κB, TNF-α, and IL-1ß ameliorated by memantine at the early days of sepsis induction, and total thiol content and SOD activity were increased. Post-septic mice showed significant disruption of recognition memory in novel object recognition (NOR) and depressive and anxiety-like behaviors in tail suspension test, elevated plus maze (EPM), and open field tests one month after sepsis. Memantine at 10 and 20 mg/kg dose-dependently ameliorated behavioral abnormalities, reduced AChE activity and MDA levels, and enhanced SOD activity and thiol content one month after sepsis. SIGNIFICANCE: These findings suggest that early treatment of septic mice with memantine could ameliorate brain inflammation and oxidative damage and prevent long-term behavioral consequences of sepsis.

Omega-3 fatty acids prevent nicotine withdrawal-induced exacerbation of anxiety and depression by affecting oxidative stress balance, inflammatory response, BDNF and serotonin metabolism in rats.

Adolescents are known to be more vulnerable than adults to the adverse effects of nicotine dependence. In the present study, we aimed to investigate whether adolescent nicotine exposure, followed by a period of abstinence, could affect the anxiety- and depressive-like behaviors in rats. For this purpose, behavioral assessments were carried out using open field test, elevated plus maze and forced swimming test in male rats received chronic nicotine intake during adolescence followed by a period of abstinence in adulthood, compared to their control counterparts. In addition, O3 pre-treatment was done at three different doses to reveal whether it could prevent nicotine withdrawal effects. Then, animals were euthanized and the cortical concentrations of oxidative stress markers, inflammatory indices, brain-derived neurotrophic factor, serotonin and the enzymatic activity of monoamine oxidase-A were measured. Results indicated that nicotine withdrawal exacerbates the behavioral signs of anxiety through alteration of the brain oxidative stress balance, inflammatory response and serotonin metabolism. Moreover, we found that omega 3 pre-treatment significantly prevents the nicotine withdrawal-induced complications by restoration of changes in the mentioned biochemical indices. Moreover, the improving effects of O3 fatty acids were found to be dose-dependent in all experiments. Taken together, we would like to suggest the O3 fatty acids supplementation as a safe, inexpensive and effective strategy for prevention or amelioration of detrimental effects induced by nicotine withdrawal at cellular and behavioral levels.

Carvacrol attenuated neuroinflammation, oxidative stress and depression and anxiety like behaviors in lipopolysaccharide-challenged rats.

Objective: The beneficial effect of carvacrol on neuroinflammation, oxidative damage of brain tissue, and depressive- and anxiety-like behaviors after lipopolysaccharide (LPS) administration were evaluated in rats. Materials and Methods: Vehicle (1% Tween 80), 1 mg/kg of LPS, and carvacrol (25, 50, or 100 mg/kg administered prior to LPS) were injected and behavioral and biochemical tests were done. Results: The results of forced swim test revealed that carvacrol attenuated immobility time and increased activity and climbing times (p<0.05 to p<0.001). The results of elevated plus maze also revealed that treatment by carvacrol prolonged the open arms time and entries and decreased the time and entries in the closed arms (p<0.05 to p<0.01). Carvacrol enhanced crossing, time, and traveled distance in the central segment of the open field and increased total crossing and distance while attenuating the peripheral zone time (p<0.05 to p<0.001). All doses of carvacrol attenuated TNF- α (tumor necrosis factor α) and NO (nitric oxide) in the brain (p<0.01 to p<0.001). The 50 and the 100 mg/kg doses of carvacrol decreased malondialdehyde (p<0.001 for both), and the 100 mg/kg dose of carvacrol increased the content of the thiol (p<0.001). Conclusion: In conclusion, carvacrol improved the behavioral consequences of LPS challenge and attenuated neuroinflammation and brain tissue oxidative stress in rats.

Crocin, the main active saffron (Crocus sativus L.) constituent, as a potential candidate to prevent anxiety and depressive-like behaviors induced by unpredictable chronic mild stress.

INTRODUCTION: Saffron, the dried stigmas of Crocus sativus L. is a famous and high-value agricultural product of Iran exclusively used for cooking purpose and well known to treat mood and cognition disorder with antioxidant and anti-inflammatory activities. However, the majority of medicinal properties of saffron are associated with its main component named Crocin. Several evidence-based studies confirmed the strong positive correlation between stress hormones, and depression. The main aim of the present study is to determine the potential antidepressant effects of crocin, saffron's constitute, in unpredictable chronic mild stress (UCMS) induced anxiety and depression in rats. MATERIALS AND METHODS: The rats were treated as 1) Vehicle with saline, 2) UCMS, 3-5) UCMS- Crocin 10, 20, and 30 mg/kg by oral gavage, 6) Vehicle with Crocin 30 mg/kg by oral gavage. Male Wistar Rats were subjected to UCMS for a total of 4 weeks. During 4 weeks, they received seven training trials. After behavioral tests, the rat brain sections were collected to examine inflammation and oxidative stress damage criteria. RESULTS: Serum corticosterone levels, cortical malondialdehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were increased in rats exposed to UCMS, while UCMS decreased IL-10 superoxide dismutase (SOD), Catalase (CAT, and thiol. In addition, UCMS decreased brain-derived neurotrophic factor (BDNF) level in cortical tissues. Crocin improved the behaviors of the UCMS rats in the open field (OF, elevated plus maze (EPM), and forced swimming (FS) tests and reversed the effects of UCMS in all measured parameters. CONCLUSION: Crocin improved UCMS -induced anxiety and depression through decreasing brain oxidative stress, inflammatory mediators, and corticosterone serum levels.

Cardiovascular protective effect of nano selenium in hypothyroid rats: protection against oxidative stress and cardiac fibrosis.

BACKGROUND: Nano selenium (Nano Sel) has many therapeutic properties including antioxidant, anticancer, and anti-inflammatory actions. OBJECTIVE: Impacts of Nano Sel administration against cardiac fibrosis and heart and aorta tissue oxidative damage observed in hypothyroid rats were explored. METHODS: The animals were randomly grouped and treated as: 1) Control; 2) Propylthiouracil (PTU) in which PTU was added to the drinking water (0.05%) to induce hypothyroidism; 3-5) PTU-Nano Sel 50, PTU-Nano Sel 100, and PTU-Nano Sel 150 groups, which received daily PTU plus 50,100 or 150 µg/kg of Nano Sel for 6 weeks intraperitoneally. The heart and aorta tissues were removed under deep anesthesia and then biochemical parameters including malondialdehyde (MDA), total thiol groups, catalase (CAT), and superoxide dismutase (SOD), as well as cardiac fibrosis were assessed. RESULTS: Hypothyroidism induced by PTU was remarkably associated with myocardial hypertrophy and perivascular fibrosis in Masson's trichrome staining. Moreover, hypothyroidism increased MDA level, while it subtracted total thiol group content and activity of SOD and CAT. Treatment with Nano Sel recovered hypothyroidism-induced cardiac fibrosis in the histological assessment. Nano Sel also promoted CAT and SOD activity and thiol content, whereas alleviated MDA levels in the heart and aorta tissues. CONCLUSION: Results propose that administration of Nano Sel exerts a protective role in the cardio vascular system via preventing cardiac fibrosis and inhibiting oxidative stress.

Metformin improved memory impairment caused by chronic ethanol consumption during adolescent to adult period of rats: Role of oxidative stress and neuroinflammation.

OBJECTIVE: Adolescence is a crucial time for brain maturation. We investigated the protective effects of metformin (Met) on behavioral changes, oxidative stress, tumor necrosis factor alpha (TNF-α) and nitrite in adulthood induced by ethanol (Eth) consumption during adolescent to adult period of rats. MATERIALS AND METHODS: The adolescence male rats (21 days old) were treated as: 1) Control, 2) Eth (Eth in drinking water (20 %)), 3-5) Eth-Met50, 100 and 150 mg/kg (Eth in drinking water and Met (50, 100, or 150 mg/kg). After 5 weeks treatment, Morris water maze (MMW) and passive avoidance (PA) tests were done. RESULTS: The latency in the MWM test was higher and the latency to enter the dark chamber in the PA test was lower in the Eth group than in control. In Eth-Met100 and 150 groups, they were less than the Eth group. Malondialdehyde (MDA) and nitrite concentration in the hippocampus and cortex of the Eth group were higher than the control group. The thiol content and catalase and superoxide dismutase (SOD) activities in hippocampal and cortical tissues of the Eth group reduced compared to the control group. TNF-α was higher in hippocampal tissues of Eth group animals. Met reversed all of these effects. CONCLUSION: Our findings showed that the protective effects of Met against chronic Eth consumption induced learning and memory impairment were accompanied by decreasing of TNF-a, nitrite and oxidative stress in adolescent rats.

The Effects of Incensole Acetate on Neuro-inflammation, Brain-Derived Neurotrophic Factor and Memory Impairment Induced by Lipopolysaccharide in Rats.

Incensole acetate (IA) is a major component of Boswellia serrata resin that has been shown to have anti-inflammatory, anti-oxidant and neuroprotective properties. The present study determined the effect of IA on lipopolysaccharide (LPS)-induced memory impairment, and hippocampal cytokines and oxidative stress indicators level. We used 32 Wistar rats (220-250 g weight) randomly divided into four groups. The control group, which only received the saline-diluted DMSO (vehicle); LPS group which received LPS and was treated with the vehicle; and two IA-treated groups which received 2.5 or 5 mg/ kg IA before LPS injection. Morris water maze (MWM) and passive avoidance (PA) tests were performed. Finally, the brains were removed and were used to assess cytokines levels and oxidative stress status. Compared to the LPS group, IA administration reduced the time spent and path traveled to reach the hidden platform during 5 days of learning in MWM while increased the time spent in the target quadrant in the probe test. Moreover, IA increased latency while decreased entry number and time spent in the dark chamber of PA test compared to the LPS group. Additionally, pre-treatment with IA attenuated interleukin(IL)-6, tumor necrosis alpha (TNF-α), glial fibrillary acidic protein (GFAP), malondialdehyde (MDA) and nitric oxide (NO) metabolites levels while increased those of IL-10, total thiol, superoxide dismutase (SOD), catalase (CAT) and brain-derived neurotrophic factor (BDNF). Our results indicated that IA improved LPS-induced learning and memory impairments. The observed effects seem to be mediated via a protective activity against neuro-inflammation and brain tissue oxidative damage and through improving BDNF.

Effect of vitamin E on cisplatin-induced memory impairment in male rats.

OBJECTIVE: Neurotoxicity is an adverse effect caused by cisplatin due to inflammation and oxidative stress in the central nervous system. The present study aimed to assess the effects of vitamin E injection on the learning and memory of rats with cisplatin-induced cognitive impairment. METHODS: Male rats were administered with cisplatin (2 mg/kg/7 day; intraperitoneally [i i.p.]) and/or vitamin E (200 mg/kg/7 day; i.p.) for 1 week, and the control group received saline solution. Spatial memory was evaluated using Morris water maze (MWM). In addition, the hippocampal concentrations of malondialdehyde (MDA), thiol, and superoxide dismutase (SOD) were measured using biochemical methods. RESULTS: According to the findings, cisplatin significantly increased the escape latency, while decreasing the time spent and travelled pathway in the target quadrant on the final trial day compared to the control group. Furthermore, pre-treatment with vitamin E significantly reversed all the results in the spatial memory test. The biochemical data indicated that vitamin E could decrease MDA activity and increase thiol and SOD activity compared to the control group. CONCLUSION: According to the results, vitamin E could improve cisplatin-induced memory impairment possibly through affecting the hippocampal oxidative status.

Beneficial effects of vitamin D on anxiety and depression-like behaviors induced by unpredictable chronic mild stress by suppression of brain oxidative stress and neuroinflammation in rats.

The objective of this study was to investigate the protective effects of vitamin D (Vit D) on anxiety and depression-like behaviors induced by unpredictable chronic mild stress and brain tissue oxidative damage criteria and neuroinflammation in rats. The rats were treated as follows: (1) control, (2) UCMS, (3-5) Vit D 100, 1000, and 10,000 iu + UCMS. Rats were subjected to UCMS for a total of 4 weeks. During week 4, they received seven training trials. The brains were then collected to examine inflammation and oxidative stress criteria. Pretreatment with Vit D enhanced performances of the rats in the elevated plus maze (EPM) and open field (OF) and forced swimming test (FST). UCMS also increased MDA and interleukin-6 (IL-6) levels while decreased CAT, SOD, and thiol. Vit D reversed the effects of UCMS. The results of the current research revealed that Vit D improved UCMS-induced anxiety and depression via decreasing brain oxidative stress and inhibiting neuroinflammation.

Angiotensin-Converting Enzyme Inhibitor Captopril: Does it Improve Renal Function in Lipopolysaccharide-induced Inflammation Model in Rats.

Renin-angiotensin system as an important regulator of renal function has also a major role in inflammation. In the present study, the effects of captopril on renal dysfunction, renal cytokine levels, and renal tissue oxidative damage were investigated in lipopolysaccharide (LPS)-induced inflammation model in rats. Treatment of five groups of the rats was carried out as follows: (1) saline as a control, (2) LPS 1 mg/kg, and (3-5) 10, 50, or 100 mg/kg captopril 30 min, respectively, before LPS. The treatments were given for 12 days. Finally, the animals were deeply anesthetized, the blood samples were obtained, and the renal tissues were removed and kept for biochemical measurements. Administration of LPS increased serum blood urea nitrogen and creatinine (P < 0.001). Pretreatment with all doses of captopril decreased these parameters (P < 0.001). LPS also increased interleukin-6 (IL-6), malondialdehyde, and nitric oxide metabolites in the renal tissues (P<0.05 - P < 0.001), which was prevented by captopril (P < 0.05 - P < 0.001). The total thiol concentration and superoxide dismutase and catalase activities in the kidney of the LPS group were lower than the control (P < 0.001), while they were enhanced when the animals were cotreated by captopril (P <0.01 - P < 0.001). The results of the present study showed that captopril improved renal function and attenuated tissue oxidative stress in LPS-induced inflammation model in rats.

Inducible nitric oxide synthase plays a role in depression- and anxiety-like behaviors chronically induced by lipopolysaccharide in rats: Evidence from inflammation and oxidative stress.

OBJECTIVE: The effects of aminoguanidine (AG) were investigated in a rat model of lipopolysaccharide (LPS)-induced anxiety- and depression-like behaviors. MATERIALS AND METHODS: The animals were allocated to five groups (n = 10 in each) and treated by: (1) saline as a control group, (2) LPS 1 mg/kg injected two hours before behavioral tests, (3-5) AG 50, 100 or 150 mg/kg before LPS. The open-field test (OFT), elevated plus maze test (EPT), and forced swimming (FS) tests were performed. The brains and blood were then collected to examine oxidative stress and inflammation criteria. RESULTS: LPS increased the immobility while decreased the active time in the FS test. In EPT, LPS decreased the time spent in the open arms, whereas it increased the time spent in the closed arms. In OFT, LPS decreased the time spent in the central zone compared with the controls. A higher dose of selenium improved the performances of the rats in behavioral tests. LPS injection also increased malondialdehyde (MDA) while it decreased thiol, superoxide dismutase (SOD), and catalase. LPS also increased interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), but decreased IL-10 in the LPS group. AG protected the brain from inflammation and oxidative damage. CONCLUSION: It was demonstrated that AG improves the behaviors of depression and anxiety in a rat model of LPS-induced anxiety- and depression-like behaviors. Moreover, the effects of AG were accompanied by improved inflammation and oxidative damage biomarkers in brain tissues.

Therapeutic potential of renin angiotensin system inhibitors in cancer cells metastasis.

Metastasis is a complex process which contributes to the dissemination of cancer cells to other organs and forms new tumor sites. The proliferation of tumor cells is a necessary step for the initiation and progression of cancers and is associated with the formation of new vessels. In the latter stages of metastasis, cancer cells may spread into the extracellular matrix and may form metastatic nodules. Despite efforts to prevent this, effective therapies are limited in the treatment of some malignancies. Among the different tumor properties which could be usefully employed as a cancer target, metastasis may be one suitable target. The renin- angiotensin system is a physiological pathway that contributes to the proliferation of tumor cells, angiogenesis and the inflammatory response in tumor tissue. Angiotensin II (ANGII), a key peptide of this pathway, induces cell proliferation through the activation of two cellular pathways (mitogen-activated protein kinase (MAPK)-STAT3 and phosphoinositide 3-kinase (PI3K) -AKT pathway). AT1-R increases angiogenesis via the elevation of angiogenic factors expression (vascular endothelial growth factor (VEGF) and matrix metallopeptidases (MMPs)). The local activation of the RAS pathway increases the expression of ICAM, VCAM and MMPs genes that are involved in the late steps of the metastasis process. There is some evidence that RAS components are expressed in metastatic tumors and RASIs (renin-angiotensin system inhibitors) could be used to reduce cancer metastasis by affecting the mechanisms involved in several different cancers. Therefore, we have summarized the effects of RASIs, observed in pre-clinical and clinical studies of cancer cell metastasis.