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Inflammopharmacology ; 27(6): 1169-1178, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31309486


AIM: This study aimed to investigate the role of the 5-HT7 receptor in fever mechanisms and its possible effect on the antipyretic mechanism of paracetamol. MATERIALS AND METHODS: The study consisted of eight experimental groups and one control group. Group I: healthy, II: LPS, III: LPS + PARA, IV: LPS + AGO, V: LPS + ANTA, VI: LPS + AGO + ANTA, VII: LPS + AGO + PARA, VIII: LPS + ANTA + PARA, and IX: LPS + AGO + ANTA + PARA. Rectal temperatures were measured with a rectal thermometer. At the end of the experiment, tissues were examined molecularly. Real-time PCR mRNA expression analyses were performed for the 5-HT7 receptor, IL-6, and TNF-α in hypothalamus tissue. RESULTS: The mean differences in rectal temperature increased in the LPS, LPS + ANTA, and LPS + AGO + ANTA groups when compared to the healthy group and decreased in the LPS + PARA, LPS + AGO, LPS + AGO + PARA, and LPS + AGO + ANTA + PARA groups when compared to the healthy group. The IL-6 and TNF-α mRNA expression increased in the LPS, LPS + ANTA, and LPS + AGO + ANTA groups when compared to the healthy group in the 2nd and 4th hours. The IL-6 and TNF-α expression decreased in the LPS + PARA, LPS + AGO, LPS + AGO + PARA, and LPS + AGO + ANTA + PARA groups when compared to the LPS group in the 2nd and 4th hours. The 5-HT7 receptor mRNA expression increased in the LPS group when compared to the healthy group in the 2nd hour. The 5-HT7 receptor mRNA expression decreased in the LPS + AGO and LPS + AGO + PARA groups when compared to the LPS group in the 2nd hour. The 5-HT7 receptor mRNA expression increased the in LPS + ANTA and LPS + ANTA + PARA groups when compared to the LPS group in the 2nd hour. CONCLUSION: The 5-HT7 receptor is a potential defense mechanism in stopping fever and the antipyretic property of paracetamol is not due to the 5-HT7 receptor.

Acetaminofen/farmacologia , Antipiréticos/farmacologia , Febre/tratamento farmacológico , Receptores de Serotonina/fisiologia , Animais , Temperatura Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Interleucina-6/genética , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/análise , Receptores de Serotonina/genética , Fator de Necrose Tumoral alfa/genética
Cutan Ocul Toxicol ; 38(3): 290-293, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31010341


Purpose: Carvone (CVN) is a natural monoterpene found in essential oils of many aromatic plant species. In this study, we investigated the protective effect of CVN against paclitaxel (PTX)-induced retinal and optic nerve cytotoxicity in rats. Methods: Twenty-four male adult Wistar albino rats (250-400 g) were randomized into four equal groups comprising six animals in each. Group 1 (control group) received intraperitoneal (i.p.) saline solution (0.5 mL/200 g) weekly for 4 weeks. Group 2 received i.p. CVN [(S)-(+)- CVN, (5S)-5-Isopropenyl-2-methyl-2-cyclohexen-1-one, C10H14, 25 mg/kg], while Group 3 received i.p. PTX (5 mg/kg) weekly for 4 weeks. Group 4 received i.p. CVN (25 mg/kg) 30 min after i.p. PTX (5 mg/kg) weekly for 4 weeks. At the end of the experimental period, retinal and optic nerve tissues were evaluated histopathologically. Results: All retinal specimens in control and CVN groups were histopathologically normal. In PTX group all eyes (6/6) demonstrated increased retinal vascularity and rosette-like structures in the outer nuclear layer, while in PTX-CVN group all eyes (6/6) demonstrated normal retinal vascularity and absence of rosette-like structures. All optic nerve specimens in control and CVN groups were histopathologically normal. In PTX group all eyes (6/6) demonstrated severe vacuolization and decrease in the number of astrocytes and oligodendrocytes, while 3 eyes (3/6) demonstrated marked single cell necrosis. In PTX-CVN group, 4 eyes (4/6) demonstrated moderate vacuolization while, 2 eyes (2/6) had none. Compared with PTX group, 1 eye (1/6) in PTX-CVN group demonstrated a decrease in numbers of astrocytes and oligodendrocytes while 5 eyes (5/6) were normal. No remarkable single cell necrosis was observed in PTX-CVN group. Conclusions: Our histopathological findings demonstrated the potential protective role of CVN against PTX-induced retinal and optic nerve cytotoxicity. CVN might be a promising molecule in counteracting oxidative stress-based cytotoxicity in the field of retinal and optic nerve disorders.

Antineoplásicos Fitogênicos/efeitos adversos , Monoterpenos Cicloexânicos/uso terapêutico , Nervo Óptico/efeitos dos fármacos , Paclitaxel/efeitos adversos , Substâncias Protetoras/uso terapêutico , Retina/efeitos dos fármacos , Animais , Masculino , Nervo Óptico/patologia , Ratos Wistar , Retina/patologia
Naunyn Schmiedebergs Arch Pharmacol ; 392(2): 135-145, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30353214


Sepsis is a life-threatening organ dysfunction condition response resulting in acute lung injury. Urotensin II (UII), an endogenous vasoactive peptide, is widely distributed in pulmonary, cardiovascular, central nervous, renal and metabolic systems, and especially in inflammatory regions. This study aimed to investigate whether urotensin II (UII) and UII receptor (UTR) antagonists play a role in the inflammatory response to sepsis-induced lung damage and they are possible therapeutic targets. In the study, 78 male Balb-c mice were used. A cecal ligation and puncture (CLP)-induced polymicrobial sepsis model was applied, and the effects of human urotensin II (agonist) and urantide and palosuran (antagonists) were investigated on lung tissues. Glutathione and malondialdehyde levels and SOD activity of lung tissues were investigated in addition to TNF-α, IL-1ß, IL-6, NF-κB, and UTR mRNA levels. Also, lung sections were histopathologically evaluated. Urantide and palosuran, UII receptor antagonists, decreased proinflammatory cytokines such as TNF-α, IL-1ß, IL-6, NF-κB, and also decreased oxidative stress parameters in lung tissue, which are markers of damage. UTR mRNA expression was increased in septic lungs, and both antagonists significantly decreased the elevated receptor level. Also, histopathological examination showed beneficial effects of both agonists on lung tissue. The results of this study help to understand the inflammatory and therapeutic contribution of the UII/UTR system on sepsis-induced lung damage. We can suggest that UTR receptor antagonists may be evaluated as a potential drug which reduces sepsis-induced lung damage in the future.

Lesão Pulmonar Aguda/genética , Receptores Acoplados a Proteínas-G/genética , Sepse/genética , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Ceco/cirurgia , Citocinas/genética , Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Ligadura , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos BALB C , NF-kappa B/genética , Fragmentos de Peptídeos/farmacologia , Quinolinas/farmacologia , Receptores Acoplados a Proteínas-G/agonistas , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Sepse/tratamento farmacológico , Sepse/metabolismo , Sepse/patologia , Superóxido Dismutase/metabolismo , Ureia/análogos & derivados , Ureia/farmacologia , Urotensinas/farmacologia
Ren Fail ; 39(1): 314-322, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28100100


Contrast media (CM) is known to have nephrotoxic adverse effects. Epigallocatechin-3-gallate (EGCG) is the most abundant and active catechin in green tea, and has strong antioxidant and anti-inflammatory properties. This study investigated whether EGCG can reduce contrast-induced nephrotoxicity (CIN), alone or with glycerol (GLY)-induced renal damage, and to understand its mechanisms of protection against toxicity, using models of GLY and CIN in rats. The rats were separated into eight groups (n = 6 in each), as follows: Healthy, GLY, CM, GLY + CM, CM + EGCG 50 mg/kg (po), GLY + CM + EGCG 50 mg/kg (po), CM + EGCG 100 mg/kg (po), and GLY + CM + EGCG 100 mg/kg (po). Both doses of EGCG protected against CM-induced renal dysfunction, as measured by serum creatinine and blood urea nitrogen (BUN). In addition, EGCG treatment markedly improved CIN-induced oxidative stress, and resulted in a significant down-regulatory effect on tumor necrosis factor (TNF)-α and nuclear factor (NF)-κB mRNA expression. Moreover, histopathological analysis showed that EGCG also attenuated CM-induced kidney damage. Considering the potential clinical use of CM and the numerous health benefits of EGCG, this study showed the protective role of multi-dose EGCG treatment on CIN and GLY-aggravated CIN through different mechanisms.

Antioxidantes/farmacologia , Catequina/análogos & derivados , Meios de Contraste/efeitos adversos , Glicerol/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Animais , Nitrogênio da Ureia Sanguínea , Catequina/farmacologia , Citocinas/sangue , Rim/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Chá