The hepatic and pulmonary effects of nitrofurantoin (40 mg/kg, intraperitoneally) were determined at 4 and 24 hr following its administration in mice fed for 10 weeks with a vitamin E sufficient, deficient or enriched diet. Liver glutathione (GSH) was reduced by nitrofurantoin at 4 hr but was unchanged 20 hr later. Nitrofurantoin did not affect liver glutathione peroxidase, glutathione reductase or superoxide dismutase activities. Liver catalase activities were decreased by nitrofurantoin at 4 hr. Lung GSH levels were increased whilst glutathione peroxidase activity was decreased at 4 and 24 hr. Lung glutathione reductase activity was reduced in certain groups. Nitrofurantoin did not affect lung superoxide dismutase, but catalase was decreased at 24 hr. Liver malondialdehyde levels were increased by nitrofurantoin in the vitamin E deficient group whilst lung malondialdehyde levels remained unchanged. Both liver and lung malondialdehyde levels were unaffected by vitamin E supplementation when compared to the vitamin E-sufficient group. These results suggest that nitrofurantoin (40 mg/kg) was deleterious to the liver and lung. Nitrofurantoin-induced lipid peroxidation was seen in vitamin E deficiency but an increase in dietary vitamin E content did not provide additional protection compared to the recommended daily allowance. The antioxidant activities of alpha-tocopherol and gamma-enriched tocotrienol were similar.
The present study aims to examine the effects of a palm-oil-derived vitamin E mixture containing tocotrienol (approximately 70%) and tocopherol (approximately 30%) on plasma lipids and on the formation of atherosclerotic plaques in rabbits given a 2% cholesterol diet. Eighteen New Zealand White rabbits (2.2-2.8 kg) were divided into three groups; group 1 (control) was fed a normal diet, group 2 (AT) was fed a 2% cholesterol diet and group 3 (PV) was fed a 2% cholesterol diet with oral palm vitamin E (60 mg/kg body weight) given daily for 10 weeks. There were no differences in the total cholesterol and triacylglycerol levels between the AT and PV groups. The PV group had a significantly higher concentrations of HDL-c and a lower TC/HDL-c ratio compared to the AT group (P < 0.003). The aortic tissue content of cholesterol and atherosclerotic lesions were comparable in both the AT and PV groups. However, the PV group had a lower content of plasma and aortic tissue malondialdehyde (P < 0.005). Our findings suggest that despite a highly atherogenic diet, palm vitamin E improved some important plasma lipid parameters, reduced lipid peroxidation but did not have an effect on the atherosclerotic plaque formation.
Down syndrome (DS) neurons are more susceptible to oxidative stress and previous studies have shown that vitamin E was able to reduce oxidative stress and improve DS neurons' viability. Therefore, this study was done to investigate the protective role of γ-tocotrienol (γT3) in DS neurons from hydrogen peroxide (H2O2) -induced oxidative stress. The pro-apoptosis tendency of γT3 was compared to α-tocopherol (αT) in non-stress condition as well.
The effects of palm gamma-tocotrienol (GGT) on oxidative stress-induced cellular ageing was investigated in normal human skin fibroblast cell lines derived from different age groups; young (21-year-old, YF), middle (40-year-old, MF) and old (68-year-old, OF). Fibroblast cells were treated with gamma-tocotrienol for 24 hours before or after incubation with IC50 dose of H2O2 for 2 hours. Changes in cell viability, telomere length and telomerase activity were assessed using the MTS assay (Promega, USA), Southern blot analysis and telomere repeat amplification protocol respectively. Results showed that treatment with different concentrations of gamma-tocotrienol increased fibroblasts viability with optimum dose of 80 microM for YF and 40 microM for both MF and OF. At higher concentrations, gamma-tocotrienol treatment caused marked decrease in cell viability with IC50 value of 200 microM (YF), 300 microM (MF) and 100 microM (OF). Exposure to H2O2 decreased cell viability in dose dependent manner, shortened telomere length and reduced telomerase activity in all age groups. The IC50 of H2O2 was found to be; YF (700 microM), MF (400 microM) and OF (100 microM). Results showed that viability increased significantly (p < 0.05) when cells were treated with 80 microM and 40 microM gamma-tocotrienol prior or after H2O2-induced oxidative stress in all age groups. In YF and OF, pretreatment with gamma-tocotrienol prevented shortening of telomere length and reduction in telomerase activity. In MF, telomerase activity increased while no changes in telomere length was observed. However, post-treatment of gamma-tocotrienol did not exert any significant effects on telomere length and telomerase activity. Thus, these data suggest that gamma-tocotrienol protects against oxidative stress-induced cellular ageing by modulating the telomere length possibly via telomerase.
Stress-induced premature senescence (SIPS) model is in vitro model of cellular aging. In this study, apoptosis was evaluated in SIPS model and in replicative senescent fibroblasts. We also compared the activity of senescence-associated beta-galactosidase (SA-beta gal) as a biomarker of cellular aging. Our results suggested that SIPS model and senescent fibroblasts might share similar mechanism of aging and apoptosis pathway.
The effects of tocotrienols on hepatocarcinogenesis in rats fed with 2-acetylaminofluorene (AAF) were followed morphologically and histologically for a period of 20 wk. No differences between treated and control rats in the morphology and histology of their livers was observed. Cell damage was extensive in the livers of AAF-treated rats but less extensive in the AAF-tocotrienols-treated rats when compared with normal and tocotrienols-treated rats. 2-Acetylaminofluorene significantly increases the activities of both plasma and liver microsomal gamma-glutamyltranspeptidase (GGT) and liver microsomal UDP-glucuronyltransferase (UDP-GT). Tocotrienols administered together with AAF significantly decrease the activities of plasma GGT after 12 and 20 wk (P less than 0.01, P less than 0.002, respectively) and liver microsomal UDP-GT after 20 wk (P less than 0.02) when compared with the controls and with rats treated only with tocotrienols. Liver microsomal GGT also showed a similar pattern to liver microsomal UDP-GT but the decrease was not significant. These results suggest that tocotrienols administered to AAF-treated rats reduce the severity of hepatocarcinogenesis.