RESUMEN
AIMS: Our aim was to evaluate whether the hydrogen sulfide (H2S) donor, 4-carboxyphenyl-isothiocyanate (4-CPI), exerts cardioprotective effect in the two kidney- one clip (2K-1C) rats through oxidative stress and MMP-2 activity attenuation and compare it with the classical H2S donor, Sodium Hydrosulfide (NaHS). MATERIALS AND METHODS: Renovascular hypertension (two kidneys-one clip; 2K-1C) was surgically induced in male Wistar rats. After two weeks, normotensive (2K) and hypertensive rats were intraperitoneally treated with vehicle (0.6 % dimethyl sulfoxide), NaHS (0.24 mg/Kg/day) or with 4-CPI (0.24 mg/Kg/day), for more 4 weeks. Systolic blood pressure (SBP) was evaluated weekly by tail-cuff plethysmography. Heart function was assessed by using the Millar catheter. Cardiac hypertrophy and fibrosis were evaluated by hematoxylin and eosin, and Picrosirius Red staining, respectively. The H2S was analyzed using WSP-1 fluorimetry and the cardiac oxidative stress was measured by lucigenin chemiluminescence and Amplex Red. MMP-2 activity was measured by in-gel gelatin or in situ zymography assays. Nox1, gp91phox, MMP-2 and the phospho-p65 subunit (Serine 279) nuclear factor kappa B (NF-κB) levels were evaluated by Western blotting. KEY FINDINGS: 4-CPI reduced blood pressure in hypertensive rats, decreased cardiac remodeling and promoted cardioprotection through the enhancement of cardiac H2S levels. An attenuation of oxidative stress, with inactivation of the p65-NF-κB/MMP-2 axis was similarly observed after NaHS or 4-CPI treatment in 2K-1C hypertension. SIGNIFICANCE: H2S is a mediator that promotes cardioprotective effects and decreases blood pressure, and 4-CPI seems to be a good candidate to reverse the maladaptive remodeling and cardiac dysfunction in renovascular hypertension.
Asunto(s)
Presión Sanguínea , Sulfuro de Hidrógeno , Metaloproteinasa 2 de la Matriz , FN-kappa B , Estrés Oxidativo , Animales , Masculino , Ratas , Presión Sanguínea/efectos de los fármacos , Cardiotónicos/farmacología , Sulfuro de Hidrógeno/farmacología , Sulfuro de Hidrógeno/metabolismo , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Hipertensión Renovascular/tratamiento farmacológico , Hipertensión Renovascular/metabolismo , Hipertensión Renovascular/fisiopatología , Isotiocianatos/farmacología , Metaloproteinasa 2 de la Matriz/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Sulfuros/farmacologíaRESUMEN
INTRODUCTION: The role of matrix metalloproteinase-2 and 9 in the metastasis and development of hypopharyngeal carcinoma has not been clarified. OBJECTIVES: To observe the relationship between matrix metalloproteinase-2, matrix metalloproteinase-9 and the metastasis, development of hypopharyngeal carcinoma. METHODS: This study included 42 hypopharyngeal cancer patients. The mRNA and protein expression levels of matrix metalloproteinase-2 and 9 in hypopharyngeal carcinoma and paracancerous tissues were detected by reverse transcription-polymerase chain reaction and Western blot. RESULTS: Reverse transcription-polymerase chain reaction detection showed that the mRNA of matrix metalloproteinase-2 and 9 was expressed in both cancer and pericarcinoma tissues, but was almost not expressed in polypoid control tissues. The expression intensity in the cancer tissue was significantly higher than that in the pericarcinoma tissue (matrix metalloproteinase-2: tâ¯ï¼â¯2.529, pâ¯=â¯0.015; matrix metalloproteinase-9: tâ¯ï¼â¯4.781, pâ¯ï¼â¯0.001). The mRNA expression in the cancer tissue was enhanced with the increase of the tumor clinical stage (matrix metalloproteinase-2: Fâ¯=â¯4.003, pâ¯=â¯0.026; matrix metalloproteinase-9: Fâ¯=â¯5.501, pâ¯=â¯0.008). Its expression intensity was associated with the metastasis of lymph nodes (N staging) and increased with the degree of lymphatic metastasis (matrix metalloproteinases-2: Fâ¯=â¯8.965, pâ¯=â¯0.005; matrix metalloproteinase-9: Fâ¯=â¯5.420, pâ¯=â¯0.025). There was no significant change in T staging of tumor. With the increase of tumor pathological stage, the mRNA expression of matrix metalloproteinase-2 and 9 was strengthened (matrix metalloproteinase-2: Fâ¯=â¯3.884, pâ¯=â¯0.029; matrix metalloproteinase-9: Fâ¯=â¯3.783, pâ¯=â¯0.032). The protein expression level of matrix metalloproteinase-2 and 9 was the same as that of mRNA. CONCLUSION: The expression of matrix metalloproteinase-2 and 9 in hypopharyngeal carcinoma was significantly higher than that in pericarcinoma tissue, and it was enhanced with the increase of clinical stage. The expression level was related to lymph node metastasis and tumor pathological stage. Thus, matrix metalloproteinase-2 and 9 may be involved in the occurrence, development, invasion and metastasis of hypopharyngeal carcinoma through a variety of mechanisms.
Asunto(s)
Neoplasias Hipofaríngeas , Metaloproteinasa 2 de la Matriz , Humanos , Ganglios Linfáticos , Metástasis Linfática , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genéticaRESUMEN
OBJECTIVE: We investigated the influence of resistance training on body composition and matrix metalloproteinase 2 activity in skeletal muscles of rats fed a high-fat diet. METHODS: Thirty-two Wistar rats were divided into four experimental groups (n = 8/each) according to diet and exercise status: Control (standard diet), Obese Control (high-fat diet), Resistance Training (standard diet) and Obese Resistance Training (high-fat diet) groups. Animals were fed a high-fat diet for 12 weeks to promote excessive weight gain. Resistance Training groups performed 12 weeks of training periods after this period in a vertical ladder three times/week. Fat percentage, fat-free mass and fat mass were assessed using dual-energy X-ray absorptiometry, and matrix metalloproteinase 2 activity in biceps and gastrocnemius muscles was analyzed using zymography. RESULTS: Resistance training significantly reduced body and fat masses and fat percentages in both trained groups (p<0.05). The maximal carrying load between trained groups was not different, but relative force was higher in the Resistance Training group (p<0.05). Of note, increased matrix metalloproteinase 2 activity was noted in the tested muscles of both trained groups (p<0.05). CONCLUSION: In conclusion, altered body composition and muscle matrix metalloproteinase 2 activity promoted by excessive weight gain were positively modified by resistance training. .