RESUMO
Epigallocatechin 3-gallate (EGCG) is a natural polyphenolic antioxidant in green tea leaves with well-known health-promoting properties. However, the influence of EGCG on a chronic animal model of depression remains to be fully investigated, and the details of the molecular and cellular changes are still unclear. Therefore, the present study aimed to investigate the antidepressant effect of EGCG in mice subjected to chronic unpredictable mild stress (CUMS). After eight consecutive weeks of CUMS, the mice were treated with EGCG (200 mg/kg b.w.) by oral gavage for two weeks. A forced swimming test (FST) was used to assess depressive symptoms. EGCG administration significantly alleviated CUMS-induced depression-like behavior in mice. EGCG also effectively decreased serum interleukin-1ß (IL-1ß) and increased the mRNA expression levels of brain-derived neurotrophic factor (BDNF) in the hippocampal CA3 region of CUMS mice. Furthermore, electron microscopic examination of CA3 neurons in CUMS mice showed morphological features of apoptosis, loss or disruption of the myelin sheath, and degenerating synapses. These neuronal injuries were diminished with the administration of EGCG. The treatment effect of EGCG in CUMS-induced behavioral alterations was comparable with that of clomipramine hydrochloride (Anafranil), a tricyclic antidepressant drug. In conclusion, our study demonstrates that the antidepressive action of EGCG involves downregulation of serum IL-1ß, upregulation of BDNF mRNA in the hippocampus, and reduction of CA3 neuronal lesions.
Assuntos
Fator Neurotrófico Derivado do Encéfalo , Depressão , Interleucina-1beta , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antidepressivos Tricíclicos/farmacologia , Antioxidantes/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Catequina/análogos & derivados , Clomipramina/farmacologia , Depressão/tratamento farmacológico , Depressão/etiologia , Depressão/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Interleucina-1beta/metabolismo , Camundongos , RNA Mensageiro/metabolismo , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Chá/metabolismoRESUMO
BACKGROUND: Methotrexate (MTX) is a commonly used chemotherapeutic drug that has adverse toxic effects on germ cells. Naringin (NG) is a natural flavanone glycoside, with different phytotherapeutic applications, and its possible protective effects against MTX-induced testicular tissue damage were investigated in this study. METHODS: Low and high doses of NG (40 and 80â mg/kg/day) were given for 10 days by intraperitoneal (i.p.) injection and MTX (20â mg/kg i.p.) was given at the 4th day of the experiment, with or without NG in rats. RESULTS: The obtained results showed that exposure to MTX increased malondialdehyde (MDA) levels and nitric oxide (NO) production compared with the control. In the meantime, MTX depleted catalse (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), and reduced glutathione (GSH) in the testicular tissue. Further, serum testosterone levels were significantly decreased in the MTX group. NG significantly counteracted the aforementioned effects of MTX; however, NG80 was more effective in restoring SOD, GR, MDA and NO. Interestingly, NG80 achieved a better improvement in the ultrastructural pattern of the testicular cells in MTX-exposed rats. CONCLUSION: These results indicated, for the first time, that NG could be a potential candidate therapy against MTX-reprotoxic impacts.
Assuntos
Flavanonas , Metotrexato , Animais , Antioxidantes/metabolismo , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Masculino , Metotrexato/toxicidade , Estresse Oxidativo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Testículo/metabolismoRESUMO
OBJECTIVES: Spirulina platensis (SP) is an edible Cyanobacterium with ethnomedicinal significance. This study aims at evaluating the beneficial effect of SP against carbon tetrachloride (CCl4)-induced liver toxicity in male rats. METHODS: Rats received intraperitoneal injections of CCl4 (2 ml/kg body weight [b.w.] per every other day) for 40 days, alone or in combination with oral treatments of SP (400 mg/kg b.w. per day). KEY FINDINGS: SP attenuated haematological disturbances, serum liver markers, hepatic necrosis and inflammation, and dyslipidemia in CCl4-intoxicated rats. SP also reduced CCl4-induced oxidative stress by increasing the activities of antioxidant enzymes, such as glutathione peroxidase, superoxide dismutase and catalase and glutathione content, and inhibiting lipid peroxidation products and nitric oxide levels in the rat liver. Further investigations revealed that SP counteracted CCl4-induced increased hepatic levels of Ki-67 (a parameter of cell proliferation), interleukin-6, and tumour necrosis factor-alpha and cyclooxygenase-2 messenger RNA expression. Noticeably, the supplementation of SP restored the decrease of proapoptotic p53 protein levels in the liver of rats treated with CCl4. CONCLUSIONS: SP prevented liver damage in CCl4-treated rats via augmentation of antioxidant defense mechanisms and inhibition of inflammatory cytokines/mediators and antiproliferative effects.
Assuntos
Antioxidantes/uso terapêutico , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Spirulina , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose , Intoxicação por Tetracloreto de Carbono/complicações , Intoxicação por Tetracloreto de Carbono/metabolismo , Intoxicação por Tetracloreto de Carbono/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/complicações , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Citocinas/metabolismo , Suplementos Nutricionais , Dislipidemias/prevenção & controle , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Inflamação/metabolismo , Inflamação/prevenção & controle , Peroxidação de Lipídeos , Fígado/metabolismo , Masculino , Óxido Nítrico/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos Wistar , Superóxido Dismutase/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: Ginkgo biloba extract (GbE) is known to contain several bioactive compounds and exhibits free radical scavenging activity. Parkinson's Disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and is associated with oxidative stress, neuroinflammation and apoptosis. OBJECTIVE: The current study aimed to investigate the neuroprotective effect of GbE in a rat model of PD induced by rotenone (ROT; a neurotoxin). METHODS: Twenty-four male albino rats were randomly divided into four groups of six rats each: normal control, GbE treated, toxin control (ROT treated) and GbE+ROT group. RESULTS: Oral administration of ROT (2.5 mg/kg b.w.) for 50 days caused an increased generation of lipid peroxidation products and significant depletion of reduced glutathione, total thiol content and activities of enzymatic antioxidants, i.e., superoxide dismutase and glutathione peroxidase in the brains of treated rats. Furthermore, ROT caused an elevation in acetylcholinesterase, interleukin-1ß, interleukin- 6 and tumor necrosis factor-α and a significant reduction in dopamine in the stratum and substantia nigra. Immunohistochemical results illustrated that ROT treatment reduced the expression of tyrosine hydroxylase (TH). GbE treatment (150 mg/kg b.w./day) significantly reduced the elevated oxidative stress markers and proinflammatory cytokines and restored the reduced antioxidant enzyme activities, DA level and TH expression. These results were confirmed by histological observations that clearly indicated a neuroprotective effect of GbE against ROT-induced PD. CONCLUSION: GbE mitigated ROT-induced PD via the inhibition of free-radical production, scavenging of ROS, and antioxidant enhancement.
Assuntos
Encéfalo/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Administração Oral , Animais , Antioxidantes/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Citocinas/metabolismo , Suplementos Nutricionais , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Ginkgo biloba , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Fármacos Neuroprotetores/administração & dosagem , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Extratos Vegetais/administração & dosagem , Distribuição Aleatória , Ratos , Rotenona/toxicidade , Superóxido Dismutase/metabolismoRESUMO
The phytochemical substances, coumarin derivatives, have demonstrated antiresorptive bone effects by suppressing osteoclast differentiation in vitro and in vivo. Recently, we have identified 5'-hydroxy auraptene (5'-HA), a coumarin derivative isolated from Lotus lalambensis Schweinf, as a novel stimulator for osteoblast differentiation. In this study, we investigated the effect of 5'-HA on osteoclast differentiation of mouse bone marrow (BM) cells. The effect of 5'-HA on BM cell proliferation and osteoclast differentiation was determined by measuring cell viability and tartrate-resistant acid phosphatase (TRAP) enzyme activity, quantification of TRAP+ multinucleated cells (TRAP+MNCs), and quantitative real-time PCR (qPCR) of osteoclastic gene expression. Regulation of NF-κB, c-Fos/NFATc1, and MAPK signaling pathways by 5'-HA during osteoclastogenesis was measured by the NF-κB reporter assay and Western blot analysis. 5'-HA significantly suppresses the receptor activator of NF-κB ligand (RANKL) induced osteoclast differentiation of BM cells in a dose-dependent manner. Consistently, treatment of BM cells with 5'-HA significantly inhibited RANKL-induced activation of NF-κB and c-Fos/NFATc1 pathways in a dose-dependent manner. Furthermore, RANKL-induced phosphorylation of ERK1/2, p-38, and JNK was significantly inhibited by 5'-HA in BM cells. In conclusion, we identified 5'-HA as a novel coumarin derivative that suppresses RANKL-induced osteoclastogenesis via inhibiting c-Fos/NFATc1 and MAPK signaling pathways.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Cumarínicos/farmacologia , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Expressão Gênica , Lotus/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quinases de Proteína Quinase Ativadas por Mitógeno/efeitos dos fármacos , NF-kappa B/metabolismo , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ligante RANK/efeitos dos fármacos , Ligante RANK/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Nigella sativa is a well-known dietary antioxidant and a valuable inhibitor of clastogenesis and carcinogenesis. The purpose of the present work was to investigate the effects of N. sativa seeds against chromosomal aberrations in primary spermatocytes and early embryonic lethality induced by CCl4 hepatotoxin in Swiss albino mice. One hundred male Swiss albino mice were randomly divided into five groups. Groups I, II, and III received only normal saline, olive oil, and aqueous suspension of N. sativa seeds (50 mg/kg b.w.), while groups IV and V were orally given CCl4 dissolved in olive oil at a dose level of 1.9 (» LD50) alone and with aqueous suspension of N. sativa seeds (50 mg/kg b.w.) alternately. Aqueous extract of N. sativa significantly reduced the elevated frequency of chromosomal aberrations induced by CCl4 in mouse primary spermatocytes. For the male-dominant lethal test, four males from each group (control and experimental) were used and each male was mated for 13 days to two untreated virgin females. On days 14-16 after breeding, all the females were evaluated for incidence of pregnancy, live implants, and fetal deaths. Treatment with 1/4 LD50 of CCl4 induced positive dominant lethal mutation, reflecting a high rate of deformations in male germ cells. Interestingly, no dominant lethal mutations were recorded in females mated to male mice treated with CCl4 plus N. sativa. Under the experimental conditions of this study, our results highlight the beneficial role of N. sativa against CCl4-induced mutagenicity.
Assuntos
Aberrações Cromossômicas , Nigella sativa/química , Extratos Vegetais/farmacologia , Sementes/química , Espermatócitos/efeitos dos fármacos , Animais , Tetracloreto de Carbono , Feminino , Masculino , CamundongosRESUMO
The present study aims to investigate the hepatoprotective effect of taurine (TAU) alone or in combination with silymarin (SIL) on CCl4-induced liver damage. Twenty five male rats were randomized into 5 groups: normal control (vehicle treated), toxin control (CCl4 treated), CCl4+TAU, CCl4+SIL and CCl4+TAU+SIL. CCl4 provoked significant increases in the levels of hepatic TBARS, NO and NOS compared to control group, but the levels of endogenous antioxidants such as SOD, GPx, GR, GST and GSH were significantly decreased. Serum pro-inflammatory and fibrogenic cytokines including TNF-α, TGF-ß1, IL-6, leptin and resistin were increased while the anti-inflammatory (adiponectin) cytokine was decreased in all treated rats. Our results also showed that CCl4 induced an increase in liver injury parameters like serum ALT, AST, ALP, GGT and bilirubin. In addition, a significant increase in liver tissue hydroxyproline (a major component of collagen) was detected in rats exposed to CCl4. Moreover, the concentrations of serum TG, TC, HDL-C, LDL-C, VLDL-C and FFA were significantly increased by CCl4. Both TAU and SIL (i.e., antioxidants) post-treatments were effectively able to relieve most of the above mentioned imbalances. However, the combination therapy was more effective than single applications in reducing TBARS levels, NO production, hydroxyproline content in fibrotic liver and the activity of serum GGT. Combined treatment (but not TAU- or SIL-alone) was also able to effectively prevent CCl4-induced decrease in adiponectin serum levels. Of note, the combined post-treatment with TAU+SIL (but not monotherapy) normalized serum FFA in CCl4-treated rats. The biochemical results were confirmed by histological and ultrastructural changes as compared to CCl4-poisoned rats. Therefore, on the basis of our work, TAU may be used in combination with SIL as an additional adjunct therapy to cure liver diseases such as fibrosis, cirrhosis and viral hepatitis.
Assuntos
Anti-Inflamatórios/uso terapêutico , Sequestradores de Radicais Livres/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Fígado/patologia , Substâncias Protetoras/uso terapêutico , Silimarina/uso terapêutico , Taurina/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Tetracloreto de Carbono , Citocinas/sangue , Sequestradores de Radicais Livres/farmacologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/ultraestrutura , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/ultraestrutura , Cirrose Hepática/sangue , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Substâncias Protetoras/farmacologia , Ratos Wistar , Silimarina/farmacologia , Taurina/farmacologiaRESUMO
This study aims to evaluate the protective role of curcumin (Curc) against hematological and biochemical changes, as well as renal pathologies induced by lead acetate [Pb (CH3COO)2·3H2O] treatment. Male albino rats were intraperitoneally treated with Pb(2+) (25 mg of lead acetate/kg b.w., once a day) alone or in combination with Curc (30 mg of Curc/kg b.w., twice a day) for 7 days. Exposure of rats to Pb(2+) caused significant decreases in hemoglobin (Hb) content, hematocrit (Ht) value, and platelet (Plt) count, while Pb(2+)-related leukocytosis was accompanied by absolute neutrophilia, monocytosis, lymphopenia, and eosinopenia. A significant rise in lipid peroxidation (LPO) and a marked drop of total antioxidant capacity (TAC) were evident in the kidney, liver, and serum of Pb(2+) group compared to that of control. Furthermore, significantly high levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), and a sharp drop in serum high-density lipoprotein (HDL-C) level were also seen in blood after injection of Pb(2+). Additionally, hepatorenal function tests were enhanced. Meanwhile, Pb(2+) produced marked histo-cytological alterations in the renal cortex. Co-administration of Curc to the Pb(2+)-treated animals restored most of the parameters mentioned above to near-normal levels/features. In conclusion, Curc appeared to be a promising agent for protection against Pb(2+)-induced toxicity.