Biomedicine & Preventive Nutrition最新文献

Degenerative conditions are associated with free radical-induced oxidative damages in the mitochondrial paraphernalia. Antimycin A (AMA) treatment of cells mimics such conditions in vitro by augmentation in ROS levels, thus causing injury to mitochondrial DNA (mtDNA), proteins and lipids, along with depolarization of mitochondrial membrane, activation of pro-apoptotic factors, resulting in apoptosis. This study investigates the potential of aqueous and methanolic extracts of Lawsonia inermis in prevention of such oxidative damage to the cell homeostasis. The extracts significantly mitigated membrane damages induced by peroxide, along with substantial decline in AMA-induced degeneration of mitochondrial proteins and lipids in hepatic carcinoma (Hep3B) cells. mtDNA analyzed for oxidative damage by assaying for 8-OHdG revealed considerable protective effect of both extracts against AMA-induced mtDNA damage. SQ-PCR of selected mtDNA genes confirmed that both extracts alleviated amplitudes of mtDNA injury. FACS analysis with JC-1 dye established that both extracts maintained homeostasis of mitochondrial membrane potential in AMA-treated cells. Extract treatments caused decline in AMA-induced discharge of cytochrome c and AIF into the cytoplasm along with consequent subjugation of apoptosis. All activities of the extracts reported in the present study significantly (P < 0.05) correlated to their total phenolic contents, thereby proving that polyphenolic constituents of the extracts alleviate cells from oxidative stress-induced injury.

The tuberculosis infection triggers in the host a complex immune response and the involvement of CD4+ lymphocytes and interferon-gamma (INF-γ) in the control processes has been reported. Since nutritional status, e.g. regarding zinc may have potent effects on the immune response, we conducted a zinc supplementation study to gain more knowledge on its effects on immune function in pulmonary tuberculosis. Twenty-one patients with pulmonary tuberculosis completed the 3-month study. Ten of them got 45 mg zinc daily and 11 of them got placebo in addition to drug therapy. Immunoglobulins in plasma and cell proliferation, IFN-γ production and CD markers in peripheral blood mononuclear cells (PBMC) were measured. >The immune system of the patients was activated as reflected by the increased concentration of immunoglobulins in plasma. Still, there was no difference in the ability of the PBMC to proliferate and produce INF-γ in response to concanavalin A between patients and controls. Moreover, there were no significant differences in these variables between the zinc-supplemented and placebo groups after 3 months. In other experiments, the addition of zinc sulphate or iron sulphate in vitro to PBMC tended to decrease the number of CD4+ cells.

Conclusions

The immune system of the tuberculosis patients maintained its activity and in response to pharmacological therapy the immune response seemed to maintain a Th1 orientation. It was not possible to document a role of zinc supplementation for the immune response.

Angiogenesis, the formation of new blood vessels is essential for the conservancy of normal cell functions. The dysfunction and/or increase in angiogenesis may lead to uncontrolled cell proliferation of cells resulting in cancer. Inhibiting angiogenic factors using natural compound has substantial hope in cancer research. Hence, we investigated syringic acid (SA), a naturally occurring phenolic acid for its antiangiogenic property using the zebrafish embryo in vivo model. Morphological observations of the SA treated embryos were analyzed to evaluate the toxicity of the compound. RBC staining was performed to evaluate the ISV inhibition in zebrafish embryos. Further, to determine the mechanism behind ISV inhibition, a real-time reverse-transcriptase polymerase chain reaction and western blot analysis was done to evaluate VEGF mRNA and protein expression respectively. Our result showed that SA didn’t affect the morphology up to 50μM. The apparent angiogenic effect was seen from 20 to 50 μM, which significantly reduced number of circulating red blood cells in ISV region compared to that of control. At 50 μM there was no visible RBC present in the ISV region of the embryos. Further, Real-time PCR and western blot analysis showed, SA inhibited VEGF mRNA expression and protein expression respectively in a dose dependent manner. These findings altogether suggest that syringic acid may have antiangiogenic activity by down regulating VEGF mediated pathway thereby having potential therapeutic benefit and promises to be a weapon against cancer.

Chemoprevention plays pivotal role in the prevention of human cancers. Morin, a bioflavonoid, has been known for its chemopreventive activities against various cancers and also in recent years, numerous investigations have shown that flavonol containing compounds induce apoptosis in various types of cancers in experimentally induced animal models. Thus the present study was aimed to understand the molecular pathway of inflammation mediated apoptosis regulation is of crucial importance for developing therapeutic agents for the intervention of mammary cancer. In this study, we investigated the protective effects of morin on DMBA-induced mammary carcinoma in Sprague-Dawley rats. Results showed that morin significantly attenuated DMBA-induced inflammation mediated apoptotic cell death. Morin effectively suppressed the down-regulation of bax and up-regulation of bcl-2. Furthermore, morin down-regulated the pro-inflammatory markers such as COX-2, NFkB, TNF-α, IL-2, and IL-1β. We also demonstrated that intrinsic mitochondrial mediated apoptotic events by morin was associated with the release of cytochrome C and apoptotic signaling pathway. Therefore, these results suggest that morin can prevent mammary carcinoma under DMBA-induced conditions by inducing cancer cell death through apoptotic events and thus suggest that it may be clinically evaluated for the chemoprevention of mammary carcinoma.

The sclerotia of Pleurotus tuberregium are eaten as food, and used in traditional health care, for the management of hypertension, yet there is scarcity of information in the literature regarding the nature of its effect on blood pressure indices. Thus, in this study, the ability of an aqueous extract of the sclerotia to moderate blood pressure indices and pulse rates were investigated in normal and sub-chronic salt-loaded rats. The normal and treatment control groups received a diet consisting 100% of commercial feed, while the test control, reference and test treatment groups received an 8% salt-loaded diet. The extract (at 100 and 200 mg/kg body weight) and moduretics (at 1 mg/kg body weight) were orally administered daily. The normal and test control groups orally received appropriate volumes of water. The extract was screened for bioactive components using gas chromatography coupled with flame ionization detector. The flavonoids were the major components (52.82 mg/kg), and consisted of thirty-eight known flavonoids (mainly 29.03% kaempferol and 20.84% quercetin). The most abundant of the seven phytosterols and the twelve glycosides detected were sitosterol (98.16%) and amygdalin (37.56%), respectively. Compared to test control and corresponding values on day 0, the extract dose-dependently lowered the systolic, diastolic, pulse and mean arterial pressures of the salt-loaded rats; while producing a mixed effect on the pulse rates. This result suggests that the sclerotia can moderate all the blood pressure indices, and supports the use of the sclerotia in traditional health care, for the management of hypertension.

The protective effect of naringin on deltamethrin poisoning in human erythrocyte was studied using an in vitro model. Hemolysis, percentage met-hemoglobin, lipid peroxidation, glutathione, antioxidant enzymes and erythrocyte ghost protein pattern were assessed to investigate the effect of naringin. Erythrocytes at a hematocrit of 10% were incubated with 500 ppm of deltamethrin and/or 0.1 M naringin under physiological conditions of temperature and pH for 2 h. Deltamethrin significantly increased the percentage of hemolysis and met-hemoglobin in human erythrocytes as compared to the control erythrocytes and naringin significantly (P < 0.05) inhibited the percentage of hemolysis and met-hemoglobin. The levels of lipid peroxides and conjugated diene increased whereas the level of glutathione decreased significantly (P < 0.05) by deltamethrin-incubated erythrocytes. Naringin significantly inhibited the formation of lipid peroxides and conjugated diene while increased the glutathione level in erythrocytes incubated with deltamethrin. The activity of antioxidant enzymes and non-enzymic antioxidants were decreased in erythrocytes incubated with deltamethrin whereas naringin improved the activities of these antioxidant and non-enzymic antioxidants. SDS–PAGE of erythrocyte ghost protein pattern showed an alteration in the protein bands by deltamethrin poisoning but naringin significantly inhibited the alteration in protein profile. The present study divulges that naringin can reduce the abnormalities of deltamethrin poisoning by ameliorating oxidative stress. This finding raises the possibility that naringin may provide protection from pesticide poisoning.

The present study was aimed to evaluate the radioprotective efficacy of lycopene, a naturally occurring dietary carotenoid on whole body radiation-induced cellular damage in the liver of Swiss albino mice. The first phase of the study was carried out to fix the effective concentration of lycopene by performing a 30 days survival studies using different graded doses (10, 20, 40 and 80 mg/kg body weight) of lycopene administered orally to mice via intragastric intubations for seven consecutive days prior to exposure of whole body radiation (10 Gy). Based on the results of survival studies, the effective dose of lycopene was fixed which was then administered to mice orally via intragastric intubations for 7 consecutive days prior to exposure of whole body radiation (4 Gy) to evaluate its radioprotective efficacy by performing various biochemical estimations, comet assay, DNA fragmentation assay and histopathological alterations in the liver of Swiss albino mice. The results indicated that radiation-induced decrease in the levels of endogenous antioxidant enzymes and increase in lipid peroxidative index, DNA damage and comet assays were altered by pre-administration with the effective dose of lycopene (20 mg/kg body weight) which restored the antioxidant status to near normal and decreased the levels of lipid peroxidative index, DNA damage and comet assays. These results were further confirmed by histopathological examinations, which indicated that pre-administration with the effective dose of lycopene reduced the hepatic damage induced by radiation. Thus the current study shows lycopene to be an effective radioprotector against radiation-induced damage in the liver of mice.

The present study was designed to investigate the protective effects of the chelating agents desferrioxamine (DFO) and deferiprone (DFP) in aluminum intoxicated liver tissue of mice by Fourier transform infrared (FT-IR) spectroscopy. The finding reveals the alterations on the major biochemical constituents, such as lipids, proteins, collagen, glycogen and nucleic acids of liver tissue at molecular level. The significant decreased in the peak areas of CH₃ asymmetric and CH₂ symmetric groups from control 0.120 ± 0.073 and 0.924 ± 0.041 to aluminum intoxicated 0.023 ± 0.003 and 0.111 ± 0.006, but treated with chelating agents DFP and DFO + DFP improved from 0.055 ± 0.006 and 0.345 ± 0.077 to 0.091 ± 0.005 and 0.671 ± 0.046 respectively for near to control values. This result suggests that due to aluminum poisoning decreased the lipids contents in the biological system. The bands ratio at I₂₉₅₈/I₂₈₅₀ significantly decreased from control (0.380 ± 0.003) to aluminum (0.292 ± 0.013), but improved it by DFP (0.323 ± 0.002) and DFO + DFP (0.370 ± 0.001) respectively. This decreased ratio indicates a decrease in the number of methyl groups in protein fibers compared to methylene groups in aluminum intoxicated liver tissue. The significant decreased in the peak areas of amide I and amide II groups from control 3.362 ± 0.152 and 1.980 ± 0.225 to aluminum intoxicated 0.713 ± 0.022 and 0.258 ± 0.020, but treated with DFP and DFO + DFP enhanced from 1.428 ± 0.140 and 0.763 ± 0.024 to 2.281 ± 0.144 and 1.283 ± 0.046 respectively for near to control values. This result suggests an alteration in the protein profile. Further, the absence of olefinicCH stretching band in aluminium exposure liver suggests an altered lipid levels. Therefore, FTIR can be used successfully applied to toxicological studies at molecular level.

Chemotherapy drugs act on normal cells as well as cancer cells. Therefore, in the present study, the extent of cell death induced by etoposide-induced oxidative stress and the role of Zea mays leaf extracts were followed in primary cultured chick embryo fibroblasts (normal cells). Various apoptosis related parameters like cell viability, morphological changes, nuclear changes and apoptotic index were characterized. SRB and MTT assays were used to quantify the extent of cell death in the group exposed to etoposide, plant extracts and their combination. The treatment with etoposide exhibited cytotoxity in the primary chick embryo fibroblasts cells. The number of apoptotic cells increased in the oxidant treated groups. When administered along with etoposide, the leaf extracts resulted in a significantly decreased number of apoptotic cells. The maximum inhibition of etoposide-induced apoptosis was exhibited by the methanolic extract followed by the aqueous and chloroform extracts. Zea mays leaf extracts reduced the toxicity of etoposide in the normal cells and the leaf extracts, by themselves, did not cause any damage to normal cells when treated alone. These results indicate that the Zea mays leaves can render protection to chick embryo fibroblasts against etoposide-induced cell death.

Cardiovascular disease affects more people and causes more death commonly. Heart failure mainly occurs due to myocardial infarction and it may be associated with an antioxidant deficit as well as increased myocardial oxidative stress. The aim of the present study was designed to evaluate the myocardial infarction induced by mercuric chloride and the productive role of ferulic acid in rats. At sub-lethal dose of mercury chloride (1.30 mg/kg body weight 45 days daily) administered in rat, heart tissue shows an elevated level of lipid peroxidation (LPO) content and simultaneously decreased level of cardiac marker enzymes. Occurrence of cardiotoxicity is mainly due to the accumulation of heavy metal in cardiac tissues and increase in the level of blood serum specific markers. The following serum enzymes were drastically increased. Due to the mercury toxicity, the level of alkaline phosphatase (ALP), alanine transferase (ALT), aspartate transaminasas (AST), creative phosphokinase (CPK), total cholesterol (TC) and lactate dehydrogenase (LDH) were increased. The administration of sub-lethal dose of ferulic acid (5 mg/kg body weight 45 days daily) restores all the serum marker enzymes to near-normal level. This result suggests that the administration of ferulic acid not only promotes the marker enzymes but it also acts as a protective effect of cardiac tissues against mercury chloride-induced oxidative stress.