RESUMEN
Aristolochic acid (AA) is a component of Chinese medicinal herbs, including asarum and aristolochia and has been used in Traditional Chinese Medicine for a long time. Recent studies found that AA has a cytotoxic effect resulting in nephropathy. These studies indicated that AAinduced cytotoxicity is associated with increases in oxidative stress and caspase3 activation. The present study further demonstrated that AA mainly elevates the H2O2 ratio, leading to increases in oxidative stress. Furthermore, the results indicated that AA induces cell death can via caspasedependent and independent pathways. It is desirable to identify means of inhibiting AAinduced renal damage; therefore, the present study applied an antioxidative nutrient, vitamin C, to test whether it can be employed to reduce AAinduced cell cytotoxicity. The results showed that vitamin C decreased AAinduced H2O2 levels, caspase3 activity and cytotoxicity in renal tubular cells. In conclusion, the present study was the first to demonstrate that AAinduced increases of the H2O2 ratio resulted in renal tubular cell death via caspasedependent and independent pathways, and that vitamin C can decrease AAinduced increases in H2O2 levels and caspase3 activity to attenuate AAinduced cell cytotoxicity.
Asunto(s)
Apoptosis/efectos de los fármacos , Ácidos Aristolóquicos/toxicidad , Ácido Ascórbico/farmacología , Túbulos Renales/citología , Túbulos Renales/efectos de los fármacos , Estrés Oxidativo , Animales , Aristolochia/química , Asarum/química , Caspasa 3/metabolismo , Línea Celular , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/toxicidad , Peróxido de Hidrógeno/metabolismo , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , RatasRESUMEN
GABA tea is a tea product that contains a high level of gamma-aminobutyric acid (GABA). This study investigated the effects of GABA tea on the heart in a diabetic rat model. Male Wistar rats were injected with 55mg/kg streptozotocin (STZ) to induce diabetes for 2weeks and then orally given dosages of 4.55 and 45.5mg/kg/day GABA tea extract for 6weeks. The results revealed that fasting blood glucose levels returned to normal levels in GABA tea-treated diabetic rats, but not in the untreated diabetic rats. Additionally, GABA tea effectively inhibited cardiac fibrosis induced by STZ. Further experiments showed that the STZ-induced protein levels of tumor necrosis factor-alpha (TNF-alpha), Fas, activated caspase-8 and caspase-3 were significantly inhibited by the GABA tea treatment. Therefore, our data suggest that the inhibiting effect of GABA tea on STZ-induced cardiac fibrosis in diabetic rats may be mediated by reducing blood glucose and further attenuating TNF-alpha expression and/or Fas/Fas ligand (FasL)-mediated apoptosis. These findings will provide implications for the potential anti-diabetic properties of GABA tea.
Asunto(s)
Apoptosis , Diabetes Mellitus Experimental/patología , Proteína Ligando Fas/fisiología , Cardiopatías/prevención & control , Té , Factor de Necrosis Tumoral alfa/fisiología , Receptor fas/fisiología , Ácido gamma-Aminobutírico/administración & dosificación , Animales , Fibrosis , Masculino , Ratas , Ratas Wistar , EstreptozocinaRESUMEN
GABA tea is a tea product that contains a high level of γ-aminobutyric acid (GABA). Previous study has demonstrated a synergistic effect of GABA tea and copper ions on DNA breakage. This study further explored whether zinc (Zn), a nonredox metal, modulated DNA cleavage induced by GABA tea extract. In a cell-free system, Zn(2+) significantly enhanced GABA tea extract and (-)-epigallocatechin-3-gallate (EGCG)- or H(2)O(2)-induced DNA damage at 24 h of incubation. Additionally, low dosages of GABA tea extract (1-10 µg/mL) possessed pro-oxidant activity to increase H(2)O(2)/Zn(2+)-induced DNA cleavage in a dose-dependent profile. By use of various reactive oxygen scavengers, it was observed that glutathione, catalase, and potassium iodide effectively inhibited DNA degradation caused by the GABA tea extract/H(2)O(2)/Zn(2+) system. Moreover, the data showed that the GABA tea extract itself (0.5-5 mg/mL) could induce DNA cleavage in a long-term exposure (48 h). EGCG, but not the GABA tea extract, enhanced H(2)O(2)-induced DNA cleavage. In contrast, GABA decreased H(2)O(2)- and EGCG-induced DNA cleavage, suggesting that GABA might contribute the major effect on the antioxidant activity of GABA tea extract. Furthermore, a comet assay revealed that GABA tea extract (0.25 mg/mL) and GABA had antioxidant activity on H(2)O(2)-induced DNA breakage in human peripheral lymphocytes. Taken together, these findings indicate that GABA tea has the potential of both pro-oxidant and antioxidant. It is proposed that a balance between EGCG-induced pro-oxidation and GABA-mediated antioxidation may occur in a complex mixture of GABA tea extract.
Asunto(s)
Daño del ADN , Té/química , Zinc/farmacología , Ácido gamma-Aminobutírico/administración & dosificación , Antioxidantes/farmacología , Bacteriófago phi X 174/genética , Catalasa/farmacología , Catequina/análogos & derivados , Catequina/farmacología , Ensayo Cometa , Daño del ADN/efectos de los fármacos , ADN Viral/efectos de los fármacos , Glutatión/farmacología , Humanos , Peróxido de Hidrógeno/farmacología , Linfocitos , Oxidantes/farmacología , Oxidación-Reducción , Yoduro de Potasio/farmacologíaRESUMEN
GABA tea is a tea product that contains a high level of γ-aminobutyric acid (GABA). The oxidant and antioxidant roles of GABA tea in DNA damage were investigated in this study. DNA cleavage was observed by GABA-tea extract in the presence of copper ions. Comet assay revealed that combination of GABA-tea extract, but not pure GABA, and Cu(2+) is capable of oxidatively degrading cellular DNA in human peripheral lymphocytes. Using various reactive oxygen scavengers, we found that catalase and sodium azide effectively inhibited GABA-tea extract/Cu(II)-induced DNA degradation, suggesting the essential role of singlet oxygen and H(2)O(2) in the reaction. In addition, neocuproine inhibited the DNA degradation, confirming that Cu(I) is an intermediate in the DNA cleavage reaction. Therefore, we speculate that GABA-tea extract/Cu(II)-induced DNA damage is probably mediated through the formation of H(2)O(2) and the reduction of copper. Furthermore, our data showed that GABA-tea extract was more genotoxic and pro-oxidant than its major catechin constituent, (-)-epigallocatechin-3-gallate (EGCG), leading to DNA cleavage in the presence of Cu(2+). These findings will provide implications for the potential of GABA-tea extract in anticancer property, which may involve copper ions and the consequent pro-oxidant action.
Asunto(s)
Cobre/toxicidad , Daño del ADN , Linfocitos/efectos de los fármacos , Té , Ácido gamma-Aminobutírico/toxicidad , Bacteriófago phi X 174/genética , Ensayo Cometa , Medios de Cultivo , ADN Viral/efectos de los fármacos , Humanos , Linfocitos/ultraestructuraRESUMEN
Epidemiological studies have indicated that the exposure to carcinogenic components formed during the cooking of food might be associated with lung cancer risk of Chinese women. Previous studies have confirmed that cooking oil fumes from frying fish (COF) contained relatively high amount of benzo[a]pyrene, 2-methyl-3,8-dimethylimidazo[4,5-f] qunoxaline, benzene, and 1,3-butadiene, reported in fumes from heated soybean oil. Thus, we consider that oxidative stress induced by COF may play a role in lung cancer development among Chinese women. To verify whether the oxidative DNA damage was induced by COF, high-performance liquid chromatography (HPLC) analysis data showed that the levels of 8-hydroxydeoxyguanine (8-OH dG) were increased in a dose-dependent manner when calf thymus DNA reacted with various concentrations of COF. Since human 8-oxoguanine DNA glycosylase 1 (hOGG1) was a repair enzyme for removing 8- OH dG from damaged DNA, we hypothesized that hOGG1 mRNA may be used to assess the risk of oxidative damage induced by the exposure of COF. The results from reverse-transcription polymerase chain reaction showed that the hOGG1 mRNA expression was induced by hydrogen peroxide (H2O2) and COF in human lung adenocarcinoma CL-3 cells. To elucidate whether hOGG1 mRNA expression was an exposure biomarker of COF, a cross-sectional study of 238 subjects including 94 professional cooks, 43 housewives, and 101 COF-nonexposed control subjects was conducted. The hOGG1 mRNA expression frequencies of COF-exposed cooks (27 of 94, 28.7%) and housewives (6 of 43, 14%) were significantly higher than those of control subjects (4 of 101, 4%). After adjusting for age, sex, and smoking and drinking status, the odds risks (ORs) of housewives versus control and cooks versus control were 3.94 (95% confidence interval [CI] = 0.95-16.62) and 10.12 (95% CI = 2.83-36.15), respectively. These results indicated that hOGG1 may be adequate to act as an exposure biomarker to assess the oxidative DNA damage induced by COF. This also suggests that oxidative stress induced by COF may play a role in lung cancer development among Chinese women.