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1.
This study was designed to evaluate antidepressant‐like activity of gallic acid in Swiss young male albino mice subjected to unpredictable chronic mild stress and to explore the possible underlying mechanisms for this activity. Gallic acid (5, 10, 20 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) per se were administered daily to unstressed mice and other groups of mice subjected to unpredictable mild stress, 30 min after the injection for 21 successive days. The antidepressant‐like activity was evaluated using forced swim test (FST) and sucrose preference test. Stress significantly increased immobility period of mice in FST. Gallic acid (10 and 20 mg/kg, i.p.) and fluoxetine significantly decreased immobility period of unstressed and stressed mice in FST and prevented the stress‐induced decrease in sucrose preference, indicating significant antidepressant‐like activity. There was no significant effect on locomotor activity of the mice by the drugs. Gallic acid (10 and 20 mg/kg, i.p.) significantly decreased Monoamine oxidase‐A (MAO‐A) activity, malondialdehyde levels, and catalase activity in unstressed mice; and significantly prevented the stress‐induced decrease in reduced glutathione and catalase activity; and also significantly prevented stress‐induced increase in MAO‐A activity, malondialdehyde levels, plasma nitrite, and corticosterone levels. Thus, gallic acid showed antidepressant‐like activity in unstressed and stressed mice probably due to its antioxidant activity and through inhibition of MAO‐A activity and decrease in plasma nitrite levels. In addition, gallic acid also showed antidepressant‐like activity in stressed mice probably through decrease in plasma corticosterone levels. 相似文献
2.
Xiuqin Li Hongze Wang Qingnian Chen Zhiqin Li Chao Liu Shengnan Yin Zhengchen You 《Fundamental & clinical pharmacology》2019,33(6):621-633
Felbamate is an anticonvulsant used in the treatment of epilepsy. In this study, we investigated the antidepressant‐like actions of felbamate in mice. The effects of felbamate were first assessed using the forced swimming test (FST) and tail suspension test (TST), and then investigated in the chronic unpredictable mild stress (CUMS) and chronic social defeat stress (CSDS) models of depression. The changes in the hippocampal brain‐derived neurotrophic factor (BDNF) signaling cascade after chronic stress and felbamate treatment were also examined. It was found that felbamate exhibited antidepressant‐like activities in the FST and TST without affecting the locomotor activity of mice. Felbamate was also effective in both the CUMS and CSDS models of depression. Moreover, felbamate administration fully restored the decreased hippocampal BDNF signaling pathway in both the CUMS‐stressed and CSDS‐stressed mice. Collectively, felbamate has antidepressant‐like actions in mice involving the hippocampal BDNF system. 相似文献
3.
Min‐Jing Liao Lian‐Feng Lin Xing Zhou Xiao‐Wen Zhou Xiao Xu Xin Cheng Qin Gao Huan‐Min Luo 《Fundamental & clinical pharmacology》2013,27(5):510-516
Chronic exposure to stress hormones might impair cognitive functions such as learning and memory, which were associated with many mood disorders and neurodegenerative diseases. In this study, we aimed to screen for effective compounds to prevent cognitive deficits induced by chronic stress. Daphnetin was found to protect the cortical neurons against dexamethasone‐induced reduction of cell viability in a dose‐dependent manner in vitro. We further evaluated its effects on chronic unpredictable stress (CUS) mice in vivo. Two and 8 mg/kg administration of daphnetin could improve the performance of stress mice in Morris water maze tests and forced swimming tests. The results suggested that daphnetin might be a potent compound to treat cognitive deficits induced by CUS. 相似文献
4.
Ismail O. Ishola Onyinyechi E. Akataobi Azeez A. Alade Olufunmilayo O. Adeyemi 《Fundamental & clinical pharmacology》2019,33(3):277-285
There is a growing number of epidemiological and molecular studies which suggest that diabetes is associated with an increased risk of Parkinson's disease (PD). Hence, in this study, the effect of glimepiride (GPD), a sulphonylurea (antidiabetic) on paraquat (PQT)‐induced Parkinsonism was evaluated in mice. Thirty‐six mice were randomly divided into six groups (n = 6) and treated orally for 21 consecutive days as follows: Group 1: vehicle (10 mL/kg), Group 2: PQT (10 mg/kg, i.p., twice per week for 3 weeks), Group 3–5: GPD (1, 2 or 4 mg/kg) + PQT (10 mg/kg, i.p., twice per week for 3 weeks), Group 6: GPD (4 mg/kg, p.o.). The effects of the treatment on motor coordination were evaluated using the rotarod performance, bar and open field tests while working memory was assayed using Y‐maze test. Paraquat injection induced significant decrease in falling time, number of crosses and percentage alternation behaviour with a concomitant increase in the duration of cataleptic behaviour in the rotarod, open field, Y‐maze and bar tests, respectively, which was ameliorated by GPD treatment. PQT also increased lipid peroxidation, peroxynitrite and TNF‐α generations as well as deficit in superoxide dismutase and GSH activities in the midbrain. PQT‐induced oxidative stress and neuroinflammation was attenuated by GPD treatment. Findings from this study showed that GPD prevents PQT‐induced motor dysfunction, memory impairment, oxidative stress and neuroinflammation through enhancement of antioxidant defense system and inhibition of pro‐inflammatory cytokine release. Thus, GPD could be a potential adjunct in the management of Parkinsonism. 相似文献
5.
Thiago Vinicius Ávila Amanda Leite Bastos Pereira Adriana De Oliveira Christoff Bruna Da Silva Soley José Ederaldo Queiroz Telles Gabrielle Jacklin Eler Adelar Bracht Aleksander Roberto Zampronio Alexandra Acco 《Fundamental & clinical pharmacology》2010,24(6):759-769
The aim of this study was to evaluate the actions of the non‐steroidal anti‐inflammatory drug flunixin‐meglumin (FM) on the changes caused by lipopolysaccharide (LPS)‐induced sepsis in the rat liver. Eight groups of five adult male Wistar rats were analysed: (1) saline injected (controls), (2) FM treated with 1.1 mg/kg, (3) FM treated with 2.2 mg/kg, (4) LPS‐injected (10 mg/kg), (5) LPS‐injected with 1.1 mg/kg FM pretreatment, (6) LPS‐injected with 2.2 mg/kg FM pretreatment, (7) LPS‐injected with 1.1 mg/kg FM post‐treatment and (8) LPS‐injected with 2.2 mg/kg FM post‐treatment. All drugs were intraperitoneally injected. The following parameters were evaluated: plasma levels of hepatic enzymes and urea, hepatic histological characteristics, antioxidant enzymes and several metabolic fluxes. The latter comprised gluconeogenesis, ureagenesis and oxygen consumption. Liver damage in LPS‐induced sepsis was characterized by histological changes, increased plasma levels of alanine aminotransferase and aspartate aminotransferase (P < 0.001) and diminished gluconeogenesis (P < 0.001) and ureagenesis (P < 0.01). LPS also induced oxidative stress as evidenced by increased catalase (P < 0.05) and superoxide dismutase activities and enhanced lipid peroxidation (P < 0.001). Pretreatment of the animals with FM minimized the histological changes and normalized, in part, all enzymatic activities. Pretreatment of the animals with FM also normalized gluconeogenesis and partly restored ureagenesis (P < 0.05). These and other results show that LPS‐induced sepsis may lead to severe liver damage, affecting both structure and function. Treatment with FM can be used to avoid this damage. The antioxidant properties of FM can be, partly at least, responsible for this protective action. 相似文献
6.
Francisca Helvira Cavalcante Melo Brinell Arcanjo Moura Damião Pergentino de Sousa Silvânia Maria Mendes de Vasconcelos Danielle Silveira Macedo Marta Maria de França Fonteles Glauce Socorro de Barros Viana Francisca Cléa Florenço de Sousa 《Fundamental & clinical pharmacology》2011,25(3):362-367
Carvacrol (5‐isopropyl‐2‐methylphenol) is a monoterpenic phenol present in the essential oil of many plants. It is the major component of the essential oil fraction of oregano and thyme. In this study, the effect of carvacrol was investigated in two behavioral models, the forced swimming and tail suspension tests in mice, to investigate the possible antidepressant effect of this substance. Additionally, the mechanisms involved in the antidepressant‐like effect of carvacrol in mice were also assessed. Carvacrol (cvc) was administered orally at single doses of 12.5, 25 and 50 mg/kg. The acute treatment of cvc decreased the immobility time in the forced swimming and tail suspension tests without accompanying changes in ambulation in the open‐field test. The anti‐immobility effect of carvacrol (25 mg/kg) was not prevented by pretreatment of mice with p‐chlorophenylalanine, prazosin and yohimbine. On the other hand, the pretreatment of mice with SCH23390 or sulpiride completely blocked the antidepressant‐like effect of carvacrol (25 mg/kg) in the forced swimming test. These results show that carvacrol presents antidepressant effects in the forced swimming and tail suspension tests; this effect seems to be dependent on its interaction with the dopaminergic system, but not with the serotonergic and noradrenergic systems. Keywords: Carvacrol; Antidepressant; Forced swimming; Tail suspension; Dopaminergic system. 相似文献
7.
Atorvastatin attenuates testosterone‐induced benign prostatic hyperplasia in rats: role of peroxisome proliferator‐activated receptor‐γ and cyclo‐oxygenase‐2
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Ismail O. Ishola Habeeb K. Tijani Olufunke O. Dosumu Charles C. Anunobi Tolulope O. Oshodi 《Fundamental & clinical pharmacology》2017,31(6):652-662
Diabetes and obesity have been reported to alter sex steroid hormone metabolism. In this study, an attempt was made to investigate the protective effect of atorvastatin (ATR) in combination with celecoxib (CEL) or pioglitazone (PIO) on testosterone‐induced BPH in rats. Male Wistar rats (200–250 g) were randomly divided into nine groups (n = 8) and orally treated as follows for 28 consecutive days: group 1: vehicle control (10 mL/kg); group 2: vehicle testosterone (10 mL/kg); groups 3 ‐ 5: ATR (0.5, 2.5, and 5 mg/kg, respectively); group 6: CEL (20 mg/kg); group 7: PIO (20 mg/kg); and groups 8–9: ATR 0.5 mg/kg, and 15 min later, animals were given CEL (20 mg/kg) or PIO (20 mg/kg), respectively. One hour post‐treatment, animals in groups 2–9 were given testosterone propionate (3 mg/kg, s.c.). Twenty‐four hours after last treatment on day 28, blood was collected for serum testosterone and prostate‐specific antigen (PSA) analysis. Prostate was harvested for biochemical and histological assays. Subcutaneous injection of testosterone increased serum levels of testosterone and PSA which was ameliorated by pretreatments of rat with ATR, celecoxib, or pioglitazone. Similarly, testosterone‐induced increase in MDA and reduction in the activity of GSH, superoxide dismutase (SOD), and catalase were attenuated by ATR. Conversely, celecoxib or pioglitazone treatment failed to affect the activity of antioxidant enzymes. The histology of the prostate showed significant improvement in prostatic cells of ATR, celecoxib, or pioglitazone treated. Findings from the study showed that atorvastatin attenuated testosterone‐induced BPH. Moreover, synergistic effect was observed when atorvastatin was combined with celecoxib. 相似文献
8.
Amit D. Kandhare Pinaki Ghosh Arvindkumar E. Ghule Subhash L. Bodhankar 《Fundamental & clinical pharmacology》2013,27(6):603-622
The aim of the present investigation was to evaluate the effect of Coenzyme Q10 and its combination with vitamin E in alcohol‐induced chronic neuropathic pain. Male Wistar rats were orally treated with alcohol (10 g/kg, 35% v/v, b.i.d.) for 10 weeks. Coenzyme Q10 (25, 50, and 100 mg/kg) and vitamin E (100 mg/kg) were coadministered orally for 1 h after ethanol administration for 10 weeks. Various nerve functions, biochemical, and molecular parameters were assessed. Chronic administration of ethanol for 10 weeks resulted significant development of neuropathic pain. Treatment with Coenzyme Q10 (50 and 100 mg/kg) for 10 weeks showed significant and dose dependently increased in level of nociceptive threshold, endogenous antioxidant, and Na,K‐ATPase enzyme. Coenzyme Q10 (50 and 100 mg/kg) significantly restored the levels of motor nerve conduction velocity and sensory nerve conduction velocity. It also showed significant decrease in levels of endogenous calcium, oxidative–nitrosative stress, TNF‐α, IL‐1β, and IL‐4 level. Alteration in protein expression of polymerase gamma (pol γ) was significantly restored the Coenzyme Q10 treatment. The important finding of the study is that, Coenzyme Q10 (100 mg/kg) and α‐tocopherol (100 mg/kg) combination‐treated rats showed more significant prevention of behavioral, biochemical, and molecular neurotoxic effect of alcohol administration than Coenzyme Q10 or α‐tocopherol alone treated group. It is evident from the finding of present investigation that plethora of mechanism including inhibition of oxido‐nitrosative stress, release of pro‐inflammatory cytokine, modulation of endogenous biomarker, and protection of pol γ protein expression simultaneously orchestrate to exhibits neuroprotective effect of Coenzyme Q10, vitamin E and their combination. 相似文献
9.
Jeferson Falcão do Amaral Maria Izabel Gomes Silva Manuel Rufino de Aquino Neto Brinell Arcanjo Moura Alyne Mara Rodrigues de Carvalho Patrícia Freire Vasconcelos José Maria Barbosa Filho Stanley Juan Chavez Gutierrez Silvânia Maria Mendes Vasconcelos Danielle Silveira Macêdo Francisca Cléa Florenço de Sousa 《Fundamental & clinical pharmacology》2013,27(5):471-482
Dehydrodieugenol, known as bis‐eugenol, is a eugenol ortho dimer, and both compounds were able to exhibit anti‐inflammatory and antioxidant activities in previous studies. Furthermore, eugenol showed antidepressant‐like effect; however, the biological actions of bis‐eugenol on experimental models for screening antidepressant activity are still unknown. The present study investigated a possible antidepressant‐like activity of bis‐eugenol in the forced swimming test (FST) and tail suspension test (TST) in mice and the involvement in the monoaminergic system in this effect. In addition, a neurochemical analysis on brain monoamines of mice acutely treated with bis‐eugenol was also conducted. Bis‐eugenol decreased the immobility time in the FST and TST without accompanying changes in ambulation in the open field test at 10 mg/kg, i.p.. Nevertheless, it induced ambulation at 25 and 50 mg/kg doses. The anti‐immobility effect of bis‐eugenol (10 and 50 mg/kg, i.p.) was prevented by pretreatment of mice with p‐chlorophenylalanine (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), yohimbine (1 mg/kg, i.p., an α2‐adrenoceptor antagonist), SCH23390 (15 μg/kg, s.c., a dopamine D1 receptor antagonist) and sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist). Monoamines analysis using high‐performance liquid chromatograph revealed significant increase in the 5‐HT, NE and DA levels in brain striatum. The present study indicates that bis‐eugenol possesses antidepressant‐like activity in FST and TST by altering dopaminergic, serotonergic and noradrenergic systems function. 相似文献
10.
Renan O. Silva Francisca Beatriz M. Sousa Samara R.B. Damasceno Nathalia S. Carvalho Valdelânia G. Silva Francisco Rodrigo M.A. Oliveira Damião P. Sousa Karoline S. Aragão André L.R. Barbosa Rivelilson M. Freitas Jand Venes R. Medeiros 《Fundamental & clinical pharmacology》2014,28(4):455-464
Studies have shown that diterpenes have anti‐inflammatory and redox‐protective pharmacological activities. The present study aimed to investigate the anti‐inflammatory properties of phytol, a diterpene alcohol, in a mouse model of acute inflammation, and phytol effect on leukocyte recruitment, cytokines levels, and oxidative stress. The anti‐inflammatory activities of phytol were assessed by measuring paw edema induced by different inflammatory agents (e.g., λ‐carrageenan, compound 48/80, histamine, serotonin, bradykinin, and prostaglandin E2 [PGE2]), myeloperoxidase (MPO) activity, peritonitis model and cytokine levels. Further, oxidative stress was evaluated by determining glutathione (GSH) levels and malondialdehyde (MDA) concentration. The results showed that phytol (7.5, 25, 50, and 75 mg/kg) significantly reduced carrageenan‐induced paw edema, in a dose‐dependent manner. In addition, phytol (75 mg/kg) inhibited compound 48/80‐, histamine‐, serotonin‐, bradykinin‐ and PGE2‐induced paw edema. It also inhibited the recruitment of total leukocytes and neutrophils; decreased MPO activity, tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) levels, and MDA concentration; and increased GSH levels during carrageenan‐induced acute inflammation. These results suggest that phytol attenuates the inflammatory response by inhibiting neutrophil migration that is partly caused by reduction in IL‐1β and TNF‐α levels and oxidative stress. 相似文献
11.
Comparative gastroprotective effect of post‐treatment with low doses of rutin and cimetidine in rats
Mary Tolulope Olaleye Afolabi Clement Akinmoladun 《Fundamental & clinical pharmacology》2013,27(2):138-145
The anti‐ulcerogenic potentials of low doses of rutin and cimetidine in ethanol‐, acetic acid‐, and stress‐induced ulcers in rats have been evaluated and compared in this study. In each model, male Wistar rats were randomly divided into six groups (I–VI). Groups II–VI were administered 1 mL/100 g ethanol orally, 0.05 mL of 20% acetic acid submucosally or kept in a cold chamber for 6 h to induce ulcer in the ethanol‐, acetic acid‐, and stress‐induced ulceration model, respectively. Thereafter, group III was post‐treated with 300 mg/kg cimetidine and groups IV–VI with 20, 40, and 80 mg/kg rutin, respectively, while the control (group I) received distilled water in Tween 20. One hour after post‐treatment, all groups were killed and the gastric ulcer index was calculated. Malondialdehyde (MDA) level, vitamin C content, and glutathione peroxidase (GPx) activity were evaluated in the gastric mucosa of animals. Post‐treatment with rutin significantly reduced ulcerogen‐induced gastric damage in all models. This effect was significant at all dose levels compared with the ulcer‐induced groups. Rutin significantly reduced the MDA levels but increased the vitamin C content and GPx activity. Ulcer index and MDA level were highest in the ethanol‐induced ulcer model while vitamin C content and GPx activity were lowest in the stress‐induced ulcer model. The study showed that all three models of ulceration appeared to be linked to oxidative stress and also ascribed significant anti‐ulcerogenic potential to rutin especially at lower doses of 20–80 mg/kg. 相似文献
12.
Modulation of heme oxygenase‐1 expression and activity affects streptozotocin‐induced diabetic nephropathy in rats
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Marwa A.M. Ali Gehan H. Heeba Azza A.K. El‐Sheikh 《Fundamental & clinical pharmacology》2017,31(5):546-557
Heme oxygenase (HO)‐1 has exhibited nephro‐protective actions in different animal models; however, its full mechanistic potential in diabetic nephropathy (DN) has not yet been elucidated. Hence, the present study has been undertaken by inducing DN in rats using streptozotocin (50 mg/kg i.p.), with or without either HO‐1 inducer; hemin (HM; 40 μmol/kg, s.c.), or HO‐1 blocker; zinc protoporphyrin‐IX (ZnPP; 50 μmol/kg, i.p.), for one month. Compared to control, rats with DN suffered from hyperglycemia and hyperlipidemia, with signs of renal damage, as assessed by distortion in renal histopathologic architecture and kidney function. Renal oxidative/nitrosative stress was evident by increased malondialdehyde, nitric oxide, myeloperoxidase, with decreased reduced glutathione, superoxide dismutase, and catalase. DN group also exhibited high renal expression of the pro‐inflammatory cytokine; tumor necrosis factor (TNF)‐α, and the apoptotic marker; caspase 3, assessed by Western blot. Renal HO‐1 protein expression and activity were increased in DN rats compared to control. Administration of HM, but not ZnPP, to DN rats improved kidney function, histopathologic features, lipid profile, TNF‐α, and caspase 3 expressions, with no effect on blood glucose level. HM increased, while ZnPP decreased renal HO‐1 activity in DN rats. It is noteworthy that neither intervention affected HO‐1 activity or renal oxidative capacity in non‐diabetic rats. Interestingly, the expression of HO‐1 was upregulated by both HM and ZnPP in DN rats. In conclusion, activation of HO‐1 via HM ameliorated renal damage in STZ‐induced DN in rats, probably through antioxidant, anti‐nitrosative, anti‐inflammatory, and anti‐apoptotic mechanisms. 相似文献
13.
Caroline Porto Leite Teixeira Carla Thiciane Vasconcelos de Melo Fernando Luiz Oliveira de Araújo Allyne Mara Rodrigues de Carvalho Maria Izabel Gomes Silva José Maria Barbosa‐Filho Danielle Silveira Macêdo Glauce Socorro de Barros Viana Francisca Cléa Florenço de Sousa 《Fundamental & clinical pharmacology》2013,27(2):129-137
In a previous study conducted by our group, riparin II (ripII) isolated from the green fruit of Aniba riparia presented antianxiety effects in mice. This study investigates a possible antidepressant activity of rip II using two predictive tests for antidepressant activity in rodents: the forced swimming test (FST) and tail suspension test (TST). Additionally, the mechanisms involved in the antidepressant‐like effect in mice were also assessed. Rip II was acute administered by intraperitoneal (i.p.) and oral (p.o) routes to male mice at doses of 25 and 50 mg/kg. Results showed that ripII at both tested doses and administration routes produced a significant decrease of immobility time in FST and TST. The pretreatment of mice with prazosin (1 mg/kg, i.p., an α1‐adrenoceptor antagonist), SCH23390 (15 μg/kg, i.p., a dopamine D1 receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist), p‐chlorophenylalanine (100 mg/kg, an inhibitor of serotonin synthesis), or NAN‐190 (0.5 mg/kg, a serotonin 5‐HT1A receptor antagonist) completely blocked the anti‐immobility effects elicited by riparin II (50 mg/kg, p.o.) in the FST. This study indicates that riparin II produces significant antidepressant‐like activity in the forced swimming and TSTs, and this effect seems to be dependent on its interaction with noradrenergic, dopaminergic, and serotonergic systems. 相似文献
14.
Melo CT de Carvalho AM Moura BA Teixeira CP Vasconcelos LF Feitosa ML de Oliveira GV Barbosa-Filho JM Chavez Gutierrez SJ de França Fonteles MM Vasconcelos SM de Sousa FC 《Fundamental & clinical pharmacology》2013,27(1):104-112
Previous work has shown that intraperitoneal administration of riparin III (ripIII) reduces immobility time in the forced swimming test (FST), which suggests potential antidepressant activity. As the mechanism of action is not completely understood, this study is aimed at investigating the antidepressant‐like action of ripIII. Following intraperitoneal administration of ripIII at doses of 25 and 50 mg/kg, there were decreases in the immobility time in the FST and tail suspension test without accompanying changes in ambulation (data not shown). The pretreatment of mice with sulpiride (50 mg/kg, i.p.), prazosin (1 mg/kg, i.p.), yohimbine (1 mg/kg, i.p.), and p‐chlorophenylalanine (PCPA, 100 mg/kg, i.p. for, four consecutive days) significantly prevented the anti‐immobility effect of ripIII in the FST. On the other hand, the anti‐immobility effect of ripIII (50 mg/kg, v.o.) was not altered by pretreatment of mice with SCH23390 (15 μg/kg, i.p.) Furthermore, ripIII potentiated the sleeping latency and sleeping time of the pentobarbital‐induced sleeping time test and also potentiated apomorphine (16 mg/kg, i.p.)‐induced hypothermia in mice. In conclusion, the present study provides evidence that the antidepressant‐like effect of ripIII is dependent on its interaction with the serotonergic, noradrenergic (α1‐ and α2‐ receptors), and dopaminergic (dopamine D2 receptors) systems. 相似文献
15.
Gentamicin (GM), an aminoglycoside, is widely employed in clinical practice for the treatment of serious Gram-negative infections. The clinical utility of GM is limited by the frequent incidence of acute renal failure. Experimental evidences suggest that oxidative and nitrosative stress play an important role in GM nephrotoxicity. Spirulina fusiformis is a blue green algae with potent free radical scavenging properties. The present study was designed to investigate renoprotective potential of S. fusiformis, against GM-induced oxidative stress and renal dysfunction. Spirulina fusiformis (500, 1000, 1500 mg/kg, p.o.) was administered 2 days before and 8 days concurrently with GM (100 mg/kg, i.p.). Renal injury was assessed by measuring serum creatinine, blood urea nitrogen and creatinine clearance and serum nitrite levels. Renal oxidative stress was determined by renal malondialdehyde levels, reduced glutathione levels and by enzymatic activity of superoxide dismutase (SOD) and catalase. Chronic GM administration resulted in marked renal oxidative and nitrosative stress and significantly deranged renal functions. Treatment with S. fusiformis significantly and dose-dependently restored renal functions, reduced lipid peroxidation and enhanced reduced glutathione levels, SOD and catalase activities. The results of present study clearly demonstrate the pivotal role of reactive oxygen species and their relation to renal dysfunction and point to the therapeutic potential of S. fusiformis in GM-induced nephrotoxicity. 相似文献
16.
Cytokines, signaling molecules of the immune system, have been implicated as a contributing factor for mood disorders such as depression. Several lines of evidence supporting this contention are briefly reviewed and caveats are introduced. Essentially, a relationship between cytokines and depression is based on the findings that: 1) proinflammatory cytokines (interleukin‐1, interleukin‐6, tumor necrosis factor‐α) and bacterial endotoxins elicit sickness behaviors (e.g., fatigue, soporific effects) and symptoms of anxiety/depression that may be attenuated by chronic antidepressant treatment, 2) cytokines induce neuroendocrine and central neurotransmitter changes reminiscent of those implicated in depression, and these effects are exacerbated by stressors, 3) severe depressive illness is accompanied by signs of immune activation and by elevations of cytokine production or levels, and 4) immunotherapy, using interleukin‐2 or interferon‐α, promotes depressive symptoms that are attenuated by antidepressant treatment. It is argued that cytokine synthesis and release, elicited upon activation of the inflammatory response system, provoke neuroendocrine and brain neurotransmitter changes that are interpreted by the brain as being stressors, and contribute to the development of depression. Furthermore, such effects are subject to a sensitization effect so that a history of stressful experiences or cytokine activation augment the response to later challenges and hence the evolution of depression 相似文献
17.
Sleep is an important physiological process responsible for the maintenance of physical, mental and emotional health of a living being. Sleep deprivation is considered risky for several pathological diseases such as anxiety and motor and cognitive dysfunctions. Sleep deprivation has recently been reported to cause oxidative damage. This study has been designed to explore the possible involvement of the GABAergic mechanism in protective effects of melatonin against 72‐h sleep deprivation‐induced behaviour modification and oxidative damage in mice. Mice were sleep‐deprived for a period of 72 h using the grid over water suspended method. Animals were divided into groups of 6–8 animals each. Melatonin (5 and 10 mg/kg), flumazenil (0.5 mg/kg), picrotoxin (0.5 mg/kg) and muscimol (0.05 mg/kg) were administered for 5 days starting 2 days before 72‐h sleep deprivation. Various behavioural tests (plus maze, zero maze, mirror chamber, actophotometer) and body weight assessment followed by oxidative stress parameters (malondialdehyde level, glutathione, catalase, nitrite and protein) were carried out. The 72‐h sleep deprivation caused significant anxiety‐like behaviour, weight loss, impaired locomotor activity and oxidative damage as compared with naïve (without sleep deprivation). Treatment with melatonin (5 mg/kg and 10 mg/kg, ip) significantly improved locomotor activity, weight loss and antianxiety effect as compared with control (sleep‐deprived). Biochemically, melatonin treatment significantly restored reduced glutathione, catalase activity, attenuated lipid peroxidation and nitrite level as compared with control animals (72‐h sleep‐deprived). Flumazenil (0.5 mg/kg) and picrotoxin (0.5 mg/kg) pretreatments with a lower dose of melatonin (5 mg/kg) significantly antagonized the protective effect of melatonin. However, muscimol (0.05 mg/kg) pretreatment with melatonin (5 mg/kg, ip) potentiated the protective effect of melatonin which was significant as compared with their effect per se. This study suggests that GABAergic modulation is involved in the protective action of melatonin against sleep deprivation‐induced anxiety‐like behaviour and associated oxidative damage. 相似文献
18.
Subchronic administration of riparin III induces antidepressive‐like effects and increases BDNF levels in the mouse hippocampus
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Auriana S. Vasconcelos Iris C.M. Oliveira Laura T.M. Vidal Gabriel C. Rodrigues Stanley J.C. Gutierrez José M. Barbosa‐Filho Silvânia M.M. Vasconcelos Marta M. de França Fonteles Danielle M. Gaspar Francisca C.F. de Sousa 《Fundamental & clinical pharmacology》2015,29(4):394-403
Riparin III (Rip III) is an alcamide isolated from Aniba riparia that has presented effects of antidepressant and anxiolytic activities in acute stress behavioral models. The trial's goal was to investigate the activity of Rip III in mice exposed to corticosterone‐induced chronic depression model. Swiss female mice, 22–25 g, were distributed in following experimental groups: control group (vehicle1: saline containing 0.1% dimethyl sulfoxide and 0.1% Tween‐80, SC+ vehicle 2: distilled water emulsified with 2% Tween‐80, PO); stressed group (corticosterone, 20 mg/kg, SC, + vehicle 2, orally); Rip III group (50 mg/kg, orally); and fluvoxamine (Flu) group (50 mg/kg, orally). The mice were exposed to the behavioral tests, and posteriorly, Brain‐derived neurotrophic factor protein levels were assessed in hippocampal samples. Statistical analysis of the data was performed by one‐way anova , followed by Newman–Keuls test. Both administrations of Rip III and Flu significantly reduced the immobility time in tail suspension and forced swimming tests after 21 days without affecting locomotor function. There was also an increase in BDNF protein levels in the mice hippocampus. These findings further support the hypothesis that Rip III could be a new pharmacological target for the treatment of mood disorders. 相似文献
19.
Effect of ursolic acid in attenuating chronic constriction injury‐induced neuropathic pain in rats
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Rafia A. Bhat Madhu C. Lingaraju Nitya N. Pathak Jaspreet Kalra Dhirendra Kumar Dinesh Kumar Surendra K. Tandan 《Fundamental & clinical pharmacology》2016,30(6):517-528
Ursolic acid (UA; 3b‐hydroxy‐12‐urs‐12‐en‐28‐oic acid), a natural pentacyclic triterpenoid carboxylic acid, has been known to possess potent anti‐inflammatory, antioxidant, and antinociceptive effects in various animal models. Therefore, this study was designed to investigate the antihyperalgesic, anti‐inflammatory, and antioxidant effects of UA at 5, 10, and 20 mg/kg of doses via per os (p.o.) route for 14 days in chronic constriction injury (CCI)‐induced neuropathic pain in rats. Pain behavior in rats was evaluated before and after UA administration via mechanical and heat hyperalgesia. CCI caused significant increase in levels of pro‐inflammatory cytokines and oxido‐nitrosative stress. In addition, significant increase in myeloperoxidase, malondialdehyde, protein carbonyl, nitric oxide (NO), and total oxidant status (TOS) levels in sciatic nerve and spinal cord concomitant with mechanical and heat hyperalgesia is also noted for CCI‐induced neuropathic pain. Administration of UA significantly reduced the increased levels of pro‐inflammatory cytokines and TOS. Further, reduced glutathione is also restored by UA. UA also showed in vitro NO and superoxide radical scavenging activity. UA has a potential in attenuating neuropathic pain behavior in CCI model which may possibly be attributed to its anti‐inflammatory and antioxidant properties. 相似文献
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Denise A.G. Tonelli Marcela Pereira Isadora P. Siba Bruno J. Martynhak Diego Correia Plínio C. Casarotto Caroline Biojone Francisco S. Guimarães Samia L.R. Joca Roberto Andreatini 《Fundamental & clinical pharmacology》2013,27(6):650-655
The objective of this study was to verify whether phenytoin modifies methylphenidate‐induced hyperlocomotion, an animal model for screening antimanic‐like drugs, and also evaluate the effect of veratrine, a voltage‐gated sodium channel opener, pretreatment on the effect of phenytoin in this model. Carbamazepine was used as a positive control. Methylphenidate (5 mg/kg, s.c.) increased open‐field locomotion, and phenytoin (5–10 mg/kg, i.p.) and carbamazepine (20 mg/kg, i.p.) blocked this effect. Veratrine (0.4 mg/kg, s.c.) pretreatment reversed the effects of phenytoin (10 mg/kg, i.p.) and carbamazepine (20 mg/kg, i.p.). Phenytoin (1–50 mg/kg, i.p.) and carbamazepine (10–20 mg/kg i.p.) alone did not change spontaneous locomotor activity. These results indicate that voltage‐gated sodium channels play an important role in antimanic‐like effects of phenytoin and carbamazepine on psychostimulant‐induced hyperlocomotion model. 相似文献