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Oxidative stress and inflammatory reaction play critical roles in ischemia/reperfusion (I/R) injury in the brain. ß-carotene (ßCAR) is a naturally occurring pigment present in fruits and vegetables that expresses antioxidant and anti-inflammatory activities. This study was conducted to investigate the involvement of Bcl2/Bax and NF-κB signaling pathways in the potential protective role of ßCAR against brain injury in a middle cerebral artery occlusion (MCAO) rat model. A focal brain ischemia model was created for 2 h, followed by reperfusion. Rats were given 10 and 20 mg/kg of ßCAR for 7 days orally before induction of ischemia, at the start of reperfusion, and 3 days after ischemia. Scores of neurological deficit were rated 24 h after induction of ischemia. Motor coordination and spontaneous coordinate activities were assessed using rotarod and activity cage, respectively. After 2 h of the last dose, the animals were killed and their brains were extracted for further examinations. The results of the study show that ßCAR diminished the score of neurological deficits and ameliorated motor coordination, balance, and locomotor activity in the I/R control group. Further, ßCAR resulted in diminution of malondialdehyde (MDA) and augmentation of reduced glutathione (GSH) contents, as well as the elevation of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) enzyme activities in the brain homogenates of I/R rats. ßCAR treatment significantly reduced nuclear factor kappa B (NF-κB) brain content and myeloperoxidase (MPO) activity and ameliorated the histological alterations in the brain tissues. ßCAR significantly suppressed Bcl-2-associated X protein (Bax) and caspase-3 expression, as well as upregulated B-cell lymphoma-2 (Bcl-2) expression, suggesting a neuroprotective potential via downregulating NF-kB and protecting the rat brain against the I/R-associated apoptotic injury.
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In the present study, we aimed to delineate the neuroprotective potential of thymol (THY) against neurotoxicity and cognitive deterioration induced by thioacetamide (TAA) in an experimental model of hepatic encephalopathy (HE). Rats received TAA (100 mg kg-1, intraperitoneally injected, three times per week) for two weeks. THY (30 and 60 mg kg-1), and Vit E (100 mg k-1) were administered daily by oral gavage for 30 days after HE induction. Supplementation with THY significantly improved liver function, reduced serum ammonia level, and ameliorated the locomotor and cognitive deficits. THY effectively modulated the alteration in oxidative stress markers, neurotransmitters, and brain ATP content. Histopathology of liver and brain tissues showed that THY had ameliorated TAA-induced damage, astrocyte swelling and brain edema. Furthermore, THY downregulated NF-kB and upregulated GFAP protein expression. In addition, THY significantly promoted CREB and BDNF expression at both mRNA and protein levels, together with enhancing brain cAMP level. In conclusion, THY exerted hepato- and neuroprotective effects against HE by mitigating hepatotoxicity, hyperammonemia and brain ATP depletion via its antioxidant, anti-inflammatory effects in addition to activation of the CREB/BDNF signaling pathway.
Assuntos
Encefalopatia Hepática , Síndromes Neurotóxicas , Trifosfato de Adenosina/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição , Encefalopatia Hepática/induzido quimicamente , Encefalopatia Hepática/tratamento farmacológico , Encefalopatia Hepática/metabolismo , Fígado/metabolismo , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Transdução de Sinais , Tioacetamida/toxicidade , Timol/farmacologiaRESUMO
Ulcerative colitis (UC) is the most common type of inflammatory bowel disease, characterized by oxidative stress and elevated pro-inflammatory cytokines. Miconazole is an azole antifungal that stimulates the expression of antioxidant enzymes via Nrf2 activation, which consequently inhibits ROS formation and NF-κB activation. Hence, the present study aimed to investigate the protective effect of miconazole, sulfasalazine (as a reference drug) and their combination on acetic acid (AA)-induced UC in a rat model which was induced by intra-rectal administration of 4% AA. Rats were pretreated with miconazole (20 and 40 mg/kg, orally) or sulfasalazine (100 mg/kg, orally), or their combination (20 mg/kg miconazole and 50 mg/Kg of sulfasalazine, orally). Pretreatment with miconazole significantly reduced wet colon weight and macroscopic scores, accompanied by a significant amelioration of the colonic architecture disorder. Moreover, the treatment also significantly decreased the malondialdehyde (MDA) level and prevented the depletion of superoxide dismutase (SOD) activity and GSH content in inflamed colons. Additionally, the treatment showed suppressive activities on pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP), and upregulated the anti-inflammatory cytokine interleukin-10 (IL-10). Moreover, the treatment upregulated the protein levels of Nrf-2 and heme oxygenase-1 (HO-1) in the colon tissue. Taken together, miconazole is effective in alleviating AA-induced colitis in rats, and the mechanism of its action is associated with the activation of Nrf2-regulated cytoprotective protein expression.
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ETHNOPHARMACOLOGICAL RELEVANCE: Chickpea was used in both greek and indian traditional medicine for hormonal related conditions as menstrual induction, acceleration of parturation, treatment of retained placenta and stimulation of lactation. Chickpea (Cicer arietinum) sprout isoflavone isolates exhibited reasonable estrogenic activities. Isoflavones, a subtype of phytoestrogens, are plant derivatives with moderate estrogenic activity that tend to have protective effects on hormonal and metabolic abnormalities of women with polycystic ovary syndrome (PCOS). AIM OF THE STUDY: In this study, we investigated the effect of UPLC/ESI-MS characterized Cicer arietinum L. seeds ethanol extract (CSE) on ovarian hormones, oxidative response and ovarian histological changes on induced PCOS rat model. MATERIALS AND METHODS: Thirty-five rats were divided into five groups including negative control, PCOS, and treatment groups. PCOS was induced using letrozole (1 mg/kg) daily orally for 21 days. Each treatment group was treated with one of the following for 28 days after induction of PCOS: clomiphene citrate (1 mg/kg), and CSE at 250 and 500 mg/kg. Ovaries and uteri were excised, weighed and their sections were used for quantitative real-time reverse transcriptase polymerase chain reaction, antioxidant assays and histomorphometric study of the ovaries. The antioxidant assays, histopathological examination, hormonal and metabolic profiles, and Cyp11a1(steroidogenic enzyme) mRNA expression were measured. RESULTS: In all treatment groups, ovarian weight was significantly decreased despite having no significant effect on uterine weight. Histomorphometric study in the treatment groups revealed a significant decrease in the number and diameter of cystic follicles, a significant increase in granulosa cell thickness while, thickness of theca cells was significantly decreased when compared to PCOS. Hormone levels, metabolic profile and antioxidant status were improved in the treatment groups. Moreover, Cyp11a1 mRNA expression was significantly downregulated in the treatment groups compared to PCOS. CONCLUSIONS: In the current study, CSE enhanced the reproductive and metabolic disorders which were associated with PCOS induction. For the first time, we have highlighted the effect of CSE in treating PCOS and its associated manifestations.
Assuntos
Cicer/química , Letrozol/toxicidade , Fitoterapia , Extratos Vegetais/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Animais , Inibidores da Aromatase/toxicidade , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Clomifeno/uso terapêutico , Relação Dose-Resposta a Droga , Antagonistas de Estrogênios/uso terapêutico , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Tamanho do Órgão , Ovário/patologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Síndrome do Ovário Policístico/induzido quimicamente , Distribuição Aleatória , RatosRESUMO
The present study investigated the gastroprotective activity of benzyl isothiocyanates (BITC) on indomethacin (IND)-induced gastric injury in a rat model and explicated the possible involved biochemical, cellular, and molecular mechanisms. The rat model with gastric ulcers was established by a single oral dose of IND (30 mg per kg b.wt). BITC (0.75 and 1.5 mg kg-1) and esomeprazole (20 mg per kg b.wt) were orally administered for 3 weeks to rats before the induction of gastric injury. Compared with the IND group, BITC could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. BITC significantly preserved the antioxidants (glutathione GSH, superoxide dismutase SOD), nitric oxide (NO), and prostaglandin E2 (PGE2) contents, while decreasing the gastric mucosal malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), and myeloperoxidase (MPO) contents. Moreover, BITC remarkably upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), hemoxygenase-1 (HO-1), and NAD(P)H : quinone oxidoreductase (NQO1). In addition, BITC activates the expression of heat shock protein 70 (HSP-70) and downregulated the expression of nuclear factor-κB (NF-κB) and caspase-3 to promote gastric mucosal cell survival. To the best of our knowledge, this study is the first published report to implicate the suppression of inflammation, oxidative stress, and Nrf2 signaling pathway as a potential mechanism for the gastroprotective activity of BITC.
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Apoptose/efeitos dos fármacos , Inflamação/tratamento farmacológico , Isotiocianatos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/farmacologia , Caspase 3/metabolismo , Esomeprazol/farmacologia , Feminino , Heme Oxigenase-1/metabolismo , Humanos , Indometacina/efeitos adversos , Inflamação/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Masculino , NAD(P)H Desidrogenase (Quinona)/metabolismo , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismoRESUMO
Acrylamide (ACR) has been previously associated with male sexual dysfunction and infertility. Eruca sativa (L.) (arugula or rocket) have been widely used in traditional remedies in Mediterranean region and western Asia and was known for its strong aphrodisiac effect since Roman times. The current study was designed to investigate LC/MS analysis of total ethanol extract Eruca sativa (L.) and the efficiency and mechanism of action of Eruca sativa seed extract (ESS) in reducing hypogonadism induced by acrylamide in male rats. Male Wistar rats were divided into 6 groups (n = 7): control group, Eruca sativa seed extract (ESS) at doses of 100 and 200 mg\kg, acrylamide (ACR), ACR + ESS 100 mg/kg, and ACR + ESS 200 mg/kg. The animals received ACR at a dose of 10 mg/kg b.wt for 60 days. Sperm indices, testicular oxidative stress, testosterone hormone, and testicular histopathology and immunohistochemistry of PCNA and caspase-3 were investigated. Moreover, the expression level of testicular B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) genes was evaluated. In respect to the LC/MS of total ethanol extract Eruca sativa (L.) seed revealed tentative identification of 39 compounds, which belongs to different classes as sulphur-containing compounds, flavonoids, phenolic acid, and fatty acids. Administration of ESS extract (100, 200 mg/kg) improved semen quality, diminished lipid peroxidation, enhanced testicular antioxidant enzyme, restored serum testosterone level, and reduced testicular degeneration and Leydig cell death in the rats intoxicated with ACR. However, the effects of ESS at the dose of 200 mg/kg were similar to that of control group. Furthermore, ESS treatment significantly induced anti-apoptotic effect indicated by elevation of both Bcl-2 and Bax expressions. Nutriceutics of ESS extract protects testis against ACR-induced testicular toxicity via normalizing testicular steroidogenesis, keeping Leydig cells, and improving oxidative stress status.
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Acrilamida , Análise do Sêmen , Acrilamida/metabolismo , Acrilamida/toxicidade , Animais , Antioxidantes/metabolismo , Apoptose , Masculino , Estresse Oxidativo , Extratos Vegetais/metabolismo , Ratos , Ratos Wistar , Testículo/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND: Acrylamide (ACR) is a widespread industrial and food contaminant that garnered considerable attention for its carcinogenic, neurotoxic, and reproductive toxic effects. The antioxidant effects of Portulaca oleracea seeds extract (POS) and its fertility-enhancing effects were inspiring to evaluate the protective potential and pinpoint the mechanisms and molecular targets of the UPLC-MS fingerprinted POS extract on ACR-induced testicular toxicity in rats. METHODS: Male Wistar rats were divided into 6 equal groups of negative control, ACR model (10 mg/kg b.wt.), POS at doses of (200 and 400 mg/kg b.wt.) and POS-treated ACR groups. All treatments were given by oral dosing every day for 60 days. RESULTS: Administration of POS extract reversed the ACR-induced epididymides weight loss with improved semen quality and count, ameliorated the ACR-decreased testicular lesion scoring, testicular oxidative stress, testicular degeneration, Leydig cell apoptosis and the dysregulated PCNA and Caspase-3 expression in a dose-dependent manner. It upregulated the declined level of serum testosterone and the expression of steroidogenic genes such as CYP11A1 and 17ß3-HSD with an obvious histologic improvement of the testes with re-establishment of the normal spermatogenic series, Sertoli and Leydig cells. CONCLUSIONS: The supplementation with POS extract may provide a potential protective effect for ACR-induced testicular dysfunction which is mediated by its antioxidant, antiapoptotic and steroidogenic modulatory effects.
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Extratos Vegetais/farmacologia , Portulaca , Espermatogênese/efeitos dos fármacos , Acrilamida , Animais , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Ratos , Ratos Wistar , SementesRESUMO
AIM: Acrylamide (ACR) is an environmental pollutant with well-demonstrated neurotoxic and neurodegenerative effects in both humans and experimental animals. The present study aimed to investigate the neuroprotective effect of Portulaca oleracea seeds extract (PSE) against ACR-induced neurotoxicity in rats and its possible underlying mechanisms. PSE was subjected to phytochemical investigation using ultra-high-performance liquid chromatography (UPLC) coupled with quantitative time of flight mass spectrometry (qTOF-MS). Multivariate, clustering and correlation data analyses were performed to assess the overall effects of PSE on ACR-challenged rats. Rats were divided into six groups including negative control, ACR-intoxicated group (10 mg/kg/day), PSE treated groups (200 and 400 mg/kg/day), and ACR + PSE treated groups (200 and 400 mg/kg/day, respectively). All treatments were given intragastrically for 60 days. PSE markedly ameliorated brain damage as evidenced by the decreased lactate dehydrogenase (LDL), increased acetylcholinesterase (AchE) activities, as well as the increased brain-derived neurotrophic factor (BDNF) that were altered by the toxic dose of ACR. In addition, PSE markedly attenuated ACR-induced histopathological alterations in the cerebrum, cerebellum, hippocampus and sciatic nerve and downregulated the ACR-inclined GFAP expression. PSE restored the oxidative status in the brain as indicated by glutathione (GSH), lipid peroxidation and increased total antioxidant capacity (TAC). PSE upregulated the mRNA expression of protein kinase B (AKT), which resulted in an upsurge in its downstream cAMP response element-binding protein (CREB)/BDNF mRNA expression in the brain tissue of ACR-intoxicated rats. All exerted PSE beneficial effects were dose-dependent, with the ACR-challenged group received PSE 400 mg/kg dose showed a close clustering to the negative control in both unsupervised principal component analysis (PCA) and supervised orthogonal partial least square discriminant analysis (OPLS-Da) alongside with the hierarchical clustering analysis (HCA). The current investigation confirmed the neuroprotective capacity of PSE against ACR-induced brain injury, and our findings indicate that AKT/CREB pathways and BDNF synthesis may play an important role in the PSE-mediated protective effects against ACR-triggered neurotoxicity.
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Acrilamida/toxicidade , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Portulaca/química , Sementes/química , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Expressão Gênica/efeitos dos fármacos , Masculino , Metabolômica , Fármacos Neuroprotetores/química , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Extratos Vegetais/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacosRESUMO
More than 90% of diabetic patients suffer from sexual dysfunction, including diminished sperm count, sperm motility, and sperm viability, and low testosterone levels. The effects of Momordica charantia (MC) were studied by estimating the blood levels of insulin, glucose, glycosylated hemoglobin (HbA1c), testosterone (TST), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in diabetic rats treated with 250 and 500 mg/kg b.w. of the total extract. Testicular antioxidants, epididymal sperm characteristics, testicular histopathology, and lesion scoring were also investigated. Testicular mRNA expression of apoptosis-related markers such as antiapoptotic B-cell lymphoma-2 (Bcl-2) and proapoptotic Bcl-2-associated X protein (Bax) were evaluated by real-time PCR. Furthermore, caspase-3 protein expression was evaluated by immunohistochemistry. MC administration resulted in a significant reduction in blood glucose and HbA1c and marked elevation of serum levels of insulin, TST, and gonadotropins in diabetic rats. It induced a significant recovery of testicular antioxidant enzymes, improved histopathological changes of the testes, and decreased spermatogenic and Sertoli cell apoptosis. MC effectively inhibited testicular apoptosis, as evidenced by upregulation of Bcl-2 and downregulation of Bax and caspase-3. Moreover, reduction in apoptotic potential in MC-treated groups was confirmed by reduction in the Bax/Bcl-2 mRNA expression ratio.
Assuntos
Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Momordica charantia/química , Extratos Vegetais/farmacologia , Espermatogênese/efeitos dos fármacos , Animais , Apoptose , Caspase 3/metabolismo , Cromatografia Líquida , Diabetes Mellitus Experimental/metabolismo , Fertilidade , Hormônio Foliculoestimulante/metabolismo , Hemoglobinas Glicadas/análise , Imuno-Histoquímica , Hormônio Luteinizante/farmacologia , Masculino , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Células de Sertoli/citologia , Células de Sertoli/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/metabolismo , Testosterona/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Osteoarthritis (OA) is a joint disease characterized by degeneration of cartilage, intra-articular inflammation, remodeling of subchondral bone and joint pain. The present study was designed to assess the therapeutic effects and the possible underlying mechanism of action of Manjarix, a herbal combination composed of ginger and turmeric powder extracts, on chemically induced osteoarthritis in rats. An OA model was generated by intra-articular injection of 50 µL (40 mg mL-1) of monosodium iodoacetate (MIA) into the right knee joint of rats. After one week of osteoarthritis induction, a comparison of the anti-inflammatory efficacy of indomethacin at an oral dose of 2 mg kg-1 daily for 4 successive weeks versus five decremental dose levels of Manjarix (1000, 500, 250, 125, and 62.5 mg kg-1) was performed. Serum inflammatory cytokines, interleukin 6, interleukin 8, and tumor necrosis factor alpha; C-telopeptide of type II collagen (CTX-II) and hyaluronic acid (HA) were measured, along with weekly assessment of the knee joint swelling. Pain-like behavior was assessed and knee radiographic and histological examination were performed to understand the extent of pain due to cartilage degradation. Manjarix significantly reduced the knee joint swelling, decreased the serum levels of IL6, TNF-α, CTX-II and HA, and reduced the pathological injury in joints, with no evidence of osteo-reactivity in the radiographic examination. Manjarix also significantly prevented MIA-induced pain behavior. These results demonstrate that Manjarix exhibits chondroprotective effects and can inhibit the OA pain induced by MIA, and thus it can be used as a potential therapeutic product for OA.
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Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Iodoacetatos/efeitos adversos , Artropatias/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Artralgia/tratamento farmacológico , Artrite Experimental/tratamento farmacológico , Cartilagem Articular , Colágeno Tipo II , Curcuma/química , Citocinas/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Zingiber officinale/química , Indometacina , Inflamação/tratamento farmacológico , Artropatias/metabolismo , Artropatias/patologia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Osteoartrite/induzido quimicamente , Extratos Vegetais/farmacologia , Ratos , Ratos WistarRESUMO
The laser pretreatment of seed is drawing pronounced attention from the scientific community for its positive impact in boosting germination, seedling , and growth of plants. In this study, the laser pretreatment of Adansonia digitata (A. digitata) seeds was evaluated. Eight laser treatments were conducted at different powers, 10, 20, 40, and 80 mW, with the two-time interval for each power at 2 and 4 min. The outcomes indicated that the most efficient irradiation was 10 mW/2 min which induces the highest germination rate and polyphenolic contents for seeds. Based on these results, the animal experimental design was processed to assess the hepatoprotective activity of A. digitata extracts obtained through the optimum laser preillumination to enhance the resistance of liver damage in mice. The total phenol and flavonoid contents and the antioxidant properties of the methanolic extracts were estimated in vitro. The CCl4 was used to induce hepatotoxicity in mice. The animals were divided into five groups. The sera of the treated animals were used for the determination of transaminases, and the liver homogenates were used for the determination of antioxidant status, and further liver tissues were subjected to verify the anti-apoptotic effect of A. digitata methanolic extract. The in vivo results showed that the methanolic extract exposed to laser treatment at 10 mW/2 min provided better hepatoprotective capacity than the other treatments. Administration of A. digitata extract not only offered a significant decrease in liver enzyme activity but also markedly improved the antioxidant status and reduced the apoptotic progression induced by CCl4 toxicity in liver tissue.
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Adansonia , Doença Hepática Induzida por Substâncias e Drogas , Animais , Antioxidantes , Germinação , Hélio , Fígado , Camundongos , Neônio , Extratos VegetaisRESUMO
Hepatic encephalopathy (HE) is a serious neuropsychiatric syndrome due to either acute or chronic hepatic failure. This study aimed to investigate the possible neuroprotective effect of chrysin, a natural flavenoid on thioacetamide (TAA)-induced hepatic encephalopathy in rats. Also the effect of chrysin on motor impairment, cognitive deficits, oxidative stress, neuroinflammation, apoptosis and histopathological damage was assessed. HE was induced in Wistar rats by intraperitoneal (i.p.) injection of TAA (200â¯mg/kg) for three alternative days. Normal and control groups received the vehicle for 21 days. Chrysin was administered orally for 21 days (25, 50, 100â¯mg/kg) and starting from day 17, rats received i.p. dose of TAA (200â¯mg/kg) at three alternative days. Then behavioral, biochemical, histopathological and immunohistochemical analyses were conducted. Chrysin improved TAA-induced motor incoordination as it reduced final falling latency time in rotarod test, ameliorated cognitive deficits in object recognition test (ORT) and attenuated serum ammonia, hepatic liver enzymes namely, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), reduced nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) brain contents. Chrysin administration also reduced Toll-4 receptor (TLR-4) gene expression, caspase-3 protein expression, hepatic necrosis and astrocyte swelling. This study depicts that chrysin exerted neuroprotective effect in TAA-induced HE rats, evidenced by improvement of cognitive deficits, motor incoordination and histopathological changes such as astrocyte swelling and vacuolization; hallmarks in HE, via reducing hyperammonia, ameliorating hepatic function, in addition to its anti-oxidant, inactivation of TLR-4/NF-κB inflammatory pathway, and anti-apoptotic effects.
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Flavonoides/uso terapêutico , Encefalopatia Hepática/prevenção & controle , Substâncias Protetoras/uso terapêutico , Tioacetamida/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Caspase 3/metabolismo , Citocinas/metabolismo , Flavonoides/farmacologia , Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Encefalopatia Hepática/induzido quimicamente , Encefalopatia Hepática/patologia , Encefalopatia Hepática/veterinária , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Stroke is the leading cause of death worldwide. Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of anti-diabetic drugs for treatment of type-2 diabetes mellitus. The aim of this study is to evaluate the possible neuroprotective effect of a dipeptidyl peptidase-4 inhibitor, vildagliptin, independent of its anti-diabetic properties in non-diabetic rats subjected to cerebral ischemia. Anesthetized Wistar rats were subjected to either left middle cerebral artery occlusion (MCAO) or sham operation followed by reperfusion after 30 min of MCAO. The other three groups were orally administered vildagliptin at 3 dose levels (2.5, 5, 10 mg/kg) for 3 successive weeks before subjected to left focal cerebral ischemia/reperfusion and till the end of the study. Neurological deficit scores and motor activity were assessed 24 h following reperfusion. Forty-eight hours following reperfusion, rats were euthanized and their left brain hemispheres were harvested and used in biochemical, histopathological, and immunohistochemical investigations. Vildagliptin pretreatment improved neurological deficit score, locomotor activity, and motor coordination in MCAO rats. Moreover, vildagliptin reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), phosphotylinosital 3 kinase (PI3K), phosphoryated of protein kinase B (p-AKT), and mechanistic target of rapamycin (mTOR) brain contents in addition to reducing protein expression of caspase-3. Also, vildagliptin showed a dose-dependent attenuation in neuronal cell loss and histopathological alterations in MCAO rats. This study proves that vildagliptin exerted a neuroprotective effect in a dose-dependent manner as shown in the attenuation of the infarct area, neuronal cell loss, and histopathological damage in MCAO rats, which may be mediated by attenuating neuronal and motor deficits, its antioxidant property, activation of the PI3K/AKT/mTOR pathway, and its anti-apoptotic effect.
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Adamantano/análogos & derivados , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Nitrilas/uso terapêutico , Pirrolidinas/uso terapêutico , Adamantano/farmacologia , Adamantano/uso terapêutico , Animais , Caspase 3/metabolismo , Inibidores da Dipeptidil Peptidase IV/farmacologia , Glutationa/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Locomoção/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Fármacos Neuroprotetores/farmacologia , Nitrilas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Pirrolidinas/farmacologia , Ratos Wistar , Serina-Treonina Quinases TOR/metabolismo , VildagliptinaRESUMO
Essential oils of some aromatic plants provide an effective nonmedicinal option to control liver fibrosis. Mentha piperita L. essential oil (MPEO) have been reported to possess protective effects against hepatotoxicity. However, its effect against liver fibrosis remains unknown. The present study investigated the antifibrogenic potential of MPEO and its underlying mechanisms. Forty male rats divided into 4 groups were used: group 1 served as normal control, group 2 (liver fibrosis) received CCl4 (2.5 mL/kg, IP, twice weekly) for 8 weeks, group 3 concurrently received CCl4 plus MPEO (50 mg/kg, IP, daily, from the 3rd week), and group 4 received MPEO only. MPOE significantly improved the liver injury markers, lipid peroxidation (LPO), antioxidant capacity, CYP2E1 gene expressionand liver histology. Furthermore, MPOE ameliorated liver fibrosis as evidenced by the reduced expression of desmin, α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1), and SMAD3 proteins. In addition, MPOE counteracted the p53 upregulation induced by CCl4 at both mRNA and protein levels. In conclusion, MPOE could effectively attenuate hepatic fibrosis mainly through improving the redox status, suppressing p53 and subsequently modulating TGF-ß1 and SMAD3 protein expression. These data promote the use of MPOE as a promising approach in antifibrotic therapy.
Assuntos
Tetracloreto de Carbono/efeitos adversos , Cirrose Hepática/tratamento farmacológico , Mentha piperita/química , Óleos Voláteis/uso terapêutico , Animais , Humanos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Óleos Voláteis/farmacologia , RatosRESUMO
Although the widespread use of titanium dioxide nanoparticles (TiO2 NPs), few studies were conducted on its hazard influence on human health. Tiron a synthetic vitamin E analog was proven to be a mitochondrial targeting antioxidant. The current investigation was performed to assess the efficacy of tiron against TiO2 NPs induced nephrotoxicity. Eighty adult male rats divided into four different groups were used: group I was the control, group II received TiO2 NPs (100mg\Kg BW), group III received TiO2 NPs plus tiron (470mg\kg BW), and group IV received tiron alone. Urea, creatinine and total protein concentrations were measured in serum to assess the renal function. Antioxidant status was estimated by determining the activities of glutathione peroxidase, superoxide dismutase, malondialdehyde (MDA) level and glutathione concentration in renal tissue. As well as Renal fibrosis was evaluated though measuring of transforming growth factor-ß1 (TGFß1) and matrix metalloproteinase 9 (MMP9) expression levels and histopathological examination. TiO2 NPs treated rats showed marked elevation of renal indices, depletion of renal antioxidant enzymes with marked increase in MDA concentration as well as significant up-regulation in fibrotic biomarkers TGFß1 and MMP9. Oral administration of tiron to TiO2 NPs treated rats significantly attenuate the renal dysfunction through decreasing of renal indices, increasing of antioxidant enzymes activities, down-regulate the expression of fibrotic genes and improving the histopathological picture for renal tissue. In conclusion, tiron was proved to attenuate the nephrotoxicity induced by TiO2 NPs through its radical scavenging and metal chelating potency.
Assuntos
Sal Dissódico do Ácido 1,2-Di-Hidroxibenzeno-3,5 Dissulfônico/farmacologia , Inflamação/tratamento farmacológico , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Nanopartículas/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Titânio/efeitos adversos , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Regulação para Baixo/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Nefropatias/metabolismo , Masculino , Malondialdeído/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Ratos , Superóxido Dismutase/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
The current investigation aimed to evaluate the antifibrogenic potential of Ocimum basilicum essential oil (OBE) and further to explore some of its underlying mechanisms. Three groups of rats were used: group I (control), group II (CCl4 model) and group III (OBE-treated) received CCl4 and OBE 2 weeks after the start of CCl4 administration. Oxidative damage was assessed by the measurement of MDA, NO, SOD, CAT, GSH and total antioxidant capacity (TAC). Liver fibrosis was assessed histopathologically by Masson's trichrome staining and α-smooth muscle actin (α-SMA) immunostaining. Expression of hepatocyte growth factor (HGF) and cytochrome P450 (CYP2EI isoform) was estimated using real-time PCR and immunohistochemistry. OBE successfully attenuated liver injury, as shown by histopathology, decreased serum transaminases and improved oxidative status of the liver. Reduced collagen deposition and α-SMA immuopositive cells indicated an abrogation of hepatic stellate cell activation by OBE. Furthermore, OBE was highly effective in stimulating HGF mRNA and protein expression and inhibiting CCl4-induced CYP2E1 down-regulation. The mechanism of antifibrogenic action of OBE is hypothesized to proceed via scavenging free radicals and activating liver regeneration by induction of HGF. These data suggest the use of OBE as a complementary treatment in liver fibrosis.