Age-related macular degeneration and protective effect of HMG Co-A reductase inhibitors (statins): results from the National Health and Nutrition Examination Survey 2005-2008.

PURPOSE: To determine the association of hydroxymethylglutarylcoenzyme A (HMG Co-A) reductase inhibitor (statin) use with the prevalence of age-related macular degeneration (AMD). METHODS: This cross-sectional study included 5604 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008, ≥ 40 years of age, who were ascertained with regard to the diagnosis of AMD, the use of statins, and comorbidities and health-related behaviors such as smoking. RESULTS: The mean age of participants denying or confirming a history of AMD was 68 (SEM 0.90) and 55 (SEM 0.36) years, respectively. Individuals 68 years of age or older who were classified as long-term users of statins had statistically significant less self-reported AMD (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.49-0.84; P=0.002), after adjusting for potential confounding variables. No significant association was found between the prevalence of AMD and statin consumption among subjects between 40 and 67 years of age (OR 1.61, 95% CI 0.85-3.03; P=0.137). CONCLUSIONS: Our results suggest a possible beneficial effect of statin intake for the prevention of AMD in individuals 68 years of age or older.

Glaucoma and vitamins A, C, and E supplement intake and serum levels in a population-based sample of the United States.

PURPOSE: To investigate the potential association between glaucoma prevalence and supplemental intake, as well as serum levels of vitamins A, C and E. METHODS: This cross-sectional study included 2912 participants in the 2005-2006 National Health and Nutrition Examination Survey, age ≥40 years, who self-reported a presence or absence of glaucoma. Participants were interviewed regarding the use of dietary supplements during the preceding 30-day period. Participants also underwent serum measurements of vitamins A, C, and E (both alpha- and gamma-tocopherol). Information on the primary outcome measure, presence or absence of glaucoma, as well as demographic information, comorbidities and health-related behaviors, was assessed via interview. RESULTS: Multivariate odds ratios for self-reported glaucoma, comparing the highest quartile of consumption to no consumption, and adjusted for potential confounding variables were 0.48 (95% confidence interval (CI) 0.13-1.82) for vitamin A, 0.47 (95% CI 0.23-0.97) for vitamin C, and 2.59 (95% CI 0.89-7.56) for vitamin E. Adjusted odds ratios for self-reported glaucoma comparing the highest vs lowest quintiles of vitamin serum levels were 1.44 (95% CI 0.79-2.62) for vitamin A, 0.94 (95% CI 0.42-2.11) for vitamin C, 1.40 (95% CI 0.70-2.81) for alpha-tocopherol, and 0.64 (95% CI 0.24-1.70) for gamma-tocopherol. CONCLUSION: Neither supplementary consumption with nor serum levels of vitamins A and E were found to be associated with glaucoma prevalence. While low- and high-dose supplementary consumption of vitamin C was found to be associated with decreased odds of glaucoma, serum levels of vitamin C did not correlate with glaucoma prevalence.

Protective effects of water extract of clam on normal and CCl4-induced damage in primary cultured rat hepatocytes.

The objective of this study was to investigate the effects of various concentrations and incubation times of water extract of clam (WEC) on glutathione, its antioxidant and the detoxification defense systems in normal and CCl4-induced oxidative damaged primary rat hepatocytes. This study showed that when the hepatocytes were treated with WEC (0.14 ~ 1.68 mg/ml), the intracellular glutathione (GSH) levels, GSH/GSSG ratio, and the activities of GSH-related enzymes (GPx, GRd, and GST) were higher than those in the control at 24 or 48 hour treatments. However, the lactate dehydrogenase (LDH) leakage and microscopic observations did not differ from those of the control. Yet, when the hepatocytes were pretreated with various concentrations of WEC for 24 hours and then exposed to 5 mM carbon tetrachloride (CCl4) for 1 hour, at concentrations of WEC between 0.42 ~ 1.68 mg/ml, the viabilities, intracellular GSH level, and activities of GST and GPx were significantly increased compared to those of the CCl4-treated control group (p < 0.05). In conclusion, WEC could improve the viability and the capabilities of detoxification and antioxidation in hepatocytes by increasing the GSH level and the activities of GSH-related enzymes.

Areca-treated fibroblasts enhance tumorigenesis of oral epithelial cells.

Several hundred million Asians chew areca nut, which is strongly associated with oral carcinogenesis in people of this region. The impacts of areca nut extract on oral target cells are largely unclear. This study hypothesized an inductive role for areca-nut-exposed stromal cells in the progression of oral carcinomas in an at-risk population. Oral fibroblasts with chronic subtoxic areca nut extract treatment exhibited growth arrest and MMP-2 activation. The supernatant of arrested oral fibroblasts activated the AKT signaling pathway in oral carcinoma cells. The enhancement of proliferation, migration, and anchorage-independent growth of oral carcinoma cells elicited by such supernatant could be abrogated by blockers against MMP-2 or AKT. Subcutaneous co-injection of arrested oral fibroblasts into nude mice significantly enhanced the tumorigenicity of xenographic oral carcinoma cells. This study concludes that areca nut extract may impair oral fibroblasts and then modulate the progression of oral epithelial oncogenesis via their secreted molecules.

Areca nut extract represses migration and differentiation while activating matrix metalloproteinase-9 of normal gingival epithelial cells.

BACKGROUND AND OBJECTIVE: Areca (betel) chewing is associated with an increase in the incidence of periodontal diseases. Aberrations in matrix metalloproteinase (MMP) expression have been reported to be associated with periodontal disease. This study investigated the effects of areca nut extract on MMP activity and the phenotype of human gingival epithelial cells. MATERIAL AND METHODS: Reverse transcription-polymerase chain reaction, western blotting and gelatin zymography were used to assay MMPs. Cell viability, mobility and detachment assays were performed to characterize the phenotypic impact. Confocal microscopy was employed to evaluate cell aggregation and the distribution of E-cadherin and F-actin. RESULTS: Treatment of gingival epithelial cells with 10 microg/mL of areca nut extract reduced its cell viability. Treatment with 5 and 10 microg/mL of areca nut extract for 24 h activated MMP-9 but not MMP-2 in gingival epithelial cells. This activation could be nuclear factor-kappaB dependent and was abrogated by 10 microM curcumin. Areca nut extract also reduced the migration and detachment of gingival epithelial cells. The differentiated cell-cell contact of gingival epithelial cells was markedly impaired by areca nut extract. This was accompanied by a disruption of distribution of E-cadherin and F-actin. CONCLUSION: The areca nut extract-mediated activation of MMP-9 in gingival epithelial cells could signify a potential periodontal pathogenesis in areca chewers. The areca nut extract-mediated inhibition of cell viability and migration, together with the changed aggregation in gingival epithelial cells, suggests that impairment of the re-epithelization underlies the process and this, in turn, might exacerbate gingival inflammation.

Determination of urinary beryllium, arsenic, and selenium in steel production workers.

Some of the most pernicious dangers of pollution arise from the presence of traces of toxic elements in the environment. In this work, we report on the determination of beryllium, arsenic, and selenium in the urine of steel production and steel quality control (QC) workers, in comparison to healthy control subjects. The urine samples were digested by a microwave system. Graphite furnace and hydride atomic absorption was used for the quantitative measurements of Be and As and Se, respectively. A quality control method for these procedures was established with concurrent analysis of Standard Trace Metals 7879 Level II and NIST SRM 2670 (Toxic Elements in Freeze Dried Urine). The results show that the urinary levels of these elements in steel production (As, 38.1 +/- 28.7 microg/L; Be, 1.58 +/- 0.46 microg/L, and Se, 69.2 +/- 28.8 +/- g/L) and in quality control workers (As, 23.9 +/- 18.1 microg/L; Be, 1.58 +/- 0.46 microg/L, and Se, 54.8 +/- 25.1 microg/L) are significantly higher than in the controls (As, 10.3 +/- 8.7 microg/L; Be, 0.83 +/- 0.46 microg/L; and Se, 32.3 +/- 13.5 microg/L). The possible connection of these elements with the etiology of disease and the possible role of selenium as a protective agent against the oncogenic and teratogenic action of other substances is discussed. We suggest the need for improvement of environmental conditions in the workplace through better ventilation and industrial hygiene practices.

Hepatoprotective effects of Arctium lappa on carbon tetrachloride- and acetaminophen-induced liver damage.

The root of Arctium lappa Linne (A. lappa) (Compositae), a perennial herb, has been cultivated for a long time as a popular vegetable. In order to investigate the hepatoprotective effects of A. lappa, male ICR mice were injected with carbon tetrachloride (CCl4, 32 microl/kg, i.p.) or acetaminophen (600 mg/kg, i.p.). A. lappa suppressed the SGOT and SGPT elevations induced by CCl4 or acetaminophen in a dose-dependent manner and alleviated the severity of liver damage based on histopathological observations. In an attempt to elucidate the possible mechanism(s) of this hepatoprotective effect, glutathione (GSH), cytochrome P-450 (P-450) and malondialdehyde (MDA) contents were studied. A. lappa reversed the decrease in GSH and P-450 induced by CCl4 and acetaminophen. It was also found that A. lappa decreased the malondialdehyde (MDA) content in CCl4 or acetaminophen-intoxicated mice. From these results, it was suggested that A. lappa could protect the liver cells from CCl4 or acetaminophen-induced liver damages, perhaps by its antioxidative effect on hepatocytes, hence eliminating the deleterious effects of toxic metabolites from CCl4 or acetaminophen.

Establishment and characterization of a cell line (HCDB-1) derived from a hamster buccal pouch carcinoma induced by DMBA and Taiwanese betel quid extract.

This study identified that the carcinogenesis of hamster buccal pouch (HBP) induced by 7,12-dimethylbenz[a]anthracene (DMBA) was greatly enhanced (18 folds) by a combination treatment with Taiwanese betel quid (BQ) extract. A new cell line, HCDB-1, has been established from induced carcinomas. The cultured monolayer cells were epithelioid in shape with irregular nuclei. They demonstrated abundant cytokeratin and tonofilaments; however, ultrastructural well-organized desmosomes were lacking. The HCDB-1 cell exhibited population doubling in 19 h and was highly tumorigenic in nude mice. A C-->T transition at codon 141 (Ala to Val) of the p53 gene was detected in this cell. This mutation is equivalent to a specific temperature-sensitive mouse p53Ala135Val mutant that causes transformation by shifting to 37.5 degrees C. HCDB-1 is the first cell line established from the HBP model of oral carcinogenesis induced by DMBA/Taiwanese BQ extract. It might be valuable for exploring the molecular pathogenesis of oral cancer.

The hepatoprotective effects of Solanum alatum Moench. on acetaminophen-induced hepatotoxicity in mice.

Solanum alatum Moench. has been shown to have a protective effect against carbon tetrachloride (CCl4)-induced liver injury. Solanum alatum treatment (100 mg/kg, p.o.) decreased the elevation of serum alanine aminotransferase (ALT; GPT) and aspartate aminotransferase (AST; GOT) induced by acetaminophen (paracetamol) (600 mg/kg, i.p.) administration. It also decreased the extent of visible necrosis in liver tissue. In addition, Solanum alatum treatment restored hepatic glutathione (GSH) depletion induced by acetaminophen (600 mg/kg, i.p.) administration. Microsomal enzyme levels such as P-450, reductase, and aniline hydroxylation enzyme were also restored to normal levels after Solanum alatum administration. The hepatoprotective mechanism may function through direct binding with acetaminophen toxic metabolites, decreasing the attraction of acetaminophen metabolites for other cellular GSH or thiol protein. Additionally, Solanum alatum treatment increased the concentration of hepatic GSH and maintained a high level activity of GSTase, which led to acceleration of the excretion of toxic acetaminophen metabolites.

Alterations of p16/MTS1 gene in oral squamous cell carcinomas from Taiwanese.

To determine the alterations of the p16/MTS1 gene in oral squamous cell carcinoma (OSCC), we examined in Taiwanese patients the mutation, deletion and methylation of p16/MTS1 in primary OSCCs associated mostly with betel quid (BQ)/tobacco use. Among 110 tumors undergoing mutational analyses, seven (6%) showed mutations in exon 2 or the intron 1/exon 2 splice site. All but one mutation disrupted the encoded proteins. Base transitions represented the vast majority (6/7) of the mutations identified in BQ/tobacco consuming subjects. It was noted that 15/56 (27%) tumors examined by restriction fragment methylation analysis revealed a significant level of methylation in different loci of exon 1 as compared with the respective non-cancerous tissue. Mutation of p16/MTS1 was exclusively identified in carcinomas of buccal mucosa, whereas methylation of the p16/MTS1 promoter region occurred preferentially in carcinomas of the tongue (54%) rather than at other sites (22%). Homozygous deletion was not found in 56 paired samples examined, nor was hemizygous deletion indicated in 12 informative cases. The results indicated aberrant methylation and mutation as the molecular abnormality of p16/MTS1 in the OSCC from Taiwanese.

The influence of propolis ethanol extract on liver microsomal enzymes and glutathione after chronic alcohol administration.

Propolis designates a series of gums, resins and balms of viscous consistency, which are gathered by honeybees from certain parts, mainly the buds and barks of plants, especially those found on coniferous trees. Bees bring propolis back to the hive, where it is modified and mixed with other substances including the bees' own wax and salivary secretions. In this study, the influences of propolis ethanol extract on chronic alcohol induced liver microsomal enzyme changes were investigated. Three grams of alcohol was added to rats' daily diet for four weeks to induce chronic alcohol liver injuries, and two different doses of propolis ethanol extract were p.o. administrated three times per day on the 28th, 29th, and 30th day. During the period of propolis administration, the ethanol diet was continued. After sacrifice, the rat livers were excised for assay of microsomal enzymes activity, glutathione (GSH) concentration, glutathione-S-transferase (GSTase) and gamma-glutamylcysteine synthetase (gamma-GCSase) activity. It was found that 30 mg/kg of propolis ethanol extract significantly prevented the elevations of total cytochrome P-450 enzymes, NADPH-dependent cytochrome C reductase, aniline hydroxylation, 7-ethoxyresorufin hydroxylation (7-ERH), 7-penthoxyresorufin hydroxylation (7-PRH), and lipid peroxidation induced by chronic ethanol administration. Additionally, propolis ethanol extract (100 mg/kg) also induced GSTase and gamma-GCSase activities and decreased glutathione levels in the liver.

p53 alterations in betel quid- and tobacco-associated oral squamous cell carcinomas from Taiwan.

Alterations of p53 have been explored in Taiwanese oral squamous cell carcinomas (OSCCs) consisting of a betel quid (BQ)/tobacco-related subgroup of 36 subjects and a tobacco-related subgroup of 13 subjects. Mutations in conserved exons were found in 12 tumors. Seven mutations were clustered in a hot-spot region mapped to a region between codons 273-282 in exon 8. The incidence of p53 mutation in BQ/tobacco tumors was 22% (8/36). The frequency of p53 allelic loss (21%, 3/14) in BQ/tobacco tumors approximates to the incidence of mutation. This is the first study demonstrating allelic deletion of p53 in such malignancies. Twenty-four of 43 samples showed positive p53 immunostaining. All tumors harboring mis-sense mutations of p53 in conserved exons exhibited nuclear protein accumulation. The incidence of mutation in conserved exons in BQ/tobacco-associated Asian OSCCs (15%) is significantly different from worldwide OSCCs (46%) related primarily to tobacco consumption (P=0.00001).

The hepatoprotective and therapeutic effects of propolis ethanol extract on chronic alcohol-induced liver injuries.

Propolis designates a mixture of gums, resins and balms, of viscous consistency, which are gathered on certain parts (buds and bark, mainly) of vegetables (especially coniferous trees) by honeybees. They bring this back to the hive, where it is modified and mixed with other substances (essentially their own wax and salivary secretions). In this study, the hepatoprotective and therapeutic effects of propolis ethanol extract on chronic alcohol-induced liver injuries were investigated in rats. 3.125 ml of 99.5% alcohol was added to animal's daily diet for four weeks to induce chronic alcohol liver injuries. After sacrifice, serum transaminases (GOT, GPT), triacylglyceride and hepatic triacylglyceride (HTG) concentration were assayed to observe liver injuries induced by chronic alcohol abuse. In addition, the phenomenon of alcohol induced fatty liver were also observed by histopathological changes. Different doses of propolis ethanol extract were p.o. administered three times per day for three days, after four weeks' alcohol administration. It was found that 10 mg/kg of propolis ethanol extract significantly decreased the elevations of serum GOT, GPT, TG and HTG. In histopathological examination, 30 mg/kg of propolis ethanol extract also remarkably decreased the hepatocellular fatty degeneration, apparent as vacuolization, induced by chronic alcohol abuse.

The protective effect of Alstonia scholaris R. Br. on hepatotoxin-induced acute liver damage.

The hepatoprotective effect of Alstonia scholaris R. Br. on liver injuries induced by carbon tetrachloride (CCl4). beta-D-galactosamine, acetaminophen and ethanol were investigated by means of serum-biochemical and histopathological examinations. Post treatment of A scholaris reduced dose-dependently the elevation of serum transaminases level and histopathological changes such as cell necrosis, inflammatory cell infiltration, which were caused by the single administration of 32 microliters/kg CCl4 or 600 mg/kg acetaminophen in mice. A. scholaris significantly lowered 288 mg/kg beta-D-galactosamine induced serum transaminases elevation in the serum-biochemical analysis in rats. A tendency was also shown to inhibit cell necrosis and inflammatory cell infiltration caused by beta-D-galactosamine in histopathological examination. All serological and histopathological effects of A. scholaris were compared with those of Bupleurum chinense, which has been reported previously as a treatment criteria of hepatitis.

Protective and therapeutic effects of huanglian-jie-du-tang on hepatotoxin-induced liver injuries.

The hepatoprotective effect of Huanglian-Jie-Du-Tang (HLJDT), a Chinese medicinal prescription, was investigated in three kinds of experimental models. The animals were treated with HLJDT (300 mg/kg, p.o.) thrice at 2, 4 and 10 hours after administration with carbon tetrachloride (32 microliters/kg, i.p.), acetaminophen (600 mg/kg, i.p.) and beta-D-galactosamine (188 mg/kg, i.p.). Significant hepatoprotective effects on carbon tetrachloride and acetaminophen induced liver injuries were noted, but no significant effect on beta-D-galactosamine induced liver injury was observed. These hepatoprotective effects were evidenced by comparing the serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) levels in HLJDT treated and untreated groups. Serum enzyme activities in the carbon tetrachloride and acetaminophen experiments were significantly lower in the treated groups while the herbal prescription has no effect on the beta-D-galactosamine experiment. These results demonstrated that Huanglian-Jie-Du-Tang has a hepatoprotective effect against experimental liver injuries induced by specific hepatotoxins, and therefore may be useful in treating some, but not all, liver injuries.

Protective and therapeutic effects of Curcuma xanthorrhiza on hepatotoxin-induced liver damage.

Curcuma xanthorrhiza Roxb. (Zingiberaceae family, commonly known as temu lawak or Javanese turmeric in Indonesia), which is found both wild and cultivated in Indonesia, has been traditionally used for medicinal purposes. C. xanthorrhiza is also used as a tonic in Indonesia. The aim of the present study is to clarify whether C. xanthorrhiza treatment may prevent acute liver damage induced by acetaminophen and carbon tetrachloride in mice. The results clearly indicated that extract of C. xanthorrhiza could reduce significantly the acute elevation of serum transaminases levels induced by the two kinds of hepatotoxins, and alleviated the degree of liver damage at 24 hours after the intraperitoneal administration of two hepatotoxins. It may be concluded that C. xanthorrhiza can protect the liver from various hepatotoxins, hence C. xanthorrhiza could be useful in the treatment of liver injuries and has promise as a kind of broad spectrum hepatoprotective agent.

Protective and therapeutic effects of ban-zhi-lian on hepatotoxin-induced liver injuries.

The hepatoprotective effect of Ban-zhi-lian was investigated in three kinds of experimental models. The animals were treated with Ban-zhi-lian (300 mg/kg, p.o.) at 2,4, and 10 hours after carbon tetrachloride (32 l/kg, i.p.), acetaminophen (600 mg/kg, i.p.), and beta-D-galactosamine (188 mg/kg, i.p.) administration. Significant protective effects from these hepatotoxins were expressed. This protection was evidenced by comparing the serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), and histopathologic examination in animals treated and untreated with Ban-zhi-lian. Serum enzyme activities were significantly lower in Ban-zhi-lian-treated groups. In the histopathologic observation, liver damage induced by three hepatotoxins was markedly improved in Ban-zhi-lian treated animals. These results demonstrated that Ban-zhi-lian has a protective effect against experimental liver damage induced by various hepatotoxins.

Hepatoprotective effects of Taiwan folk medicine: wedelia chinensis on three hepatotoxin-induced hepatotoxicity.

The hepatoprotective effects of a Taiwanese crude herb, Hwang-hua-mih-tsay (Wedelia chinensis (Osbeck) Merr.), were investigated. Acute hepatitis was induced by three hepatotoxins: carbon tetrachloride and acetaminophen in mice, and D(+)-galactosamine in rats. After treatment with W. chinensis (300 mg/kg, p.o.) at 2, 6 and 10 hours, a reduction in the elevation of serum glutamate oxaloacetic transaminase (SGOT) and glutamate pyruvic transaminase (SGPT) levels was observed at 24 hrs after hepatotoxins were administered. These serological observations were confirmed by histopathological examinations. A microscopic examination of the liver showed a marked improvement in groups receiving W. chinensis. In order to further confirm the hepatoprotective effect of W. chinensis, all pharmacological and histopathological effects were compared with Bupleurum chinense DC. (family Umbelliferae), a well documented antihepatotoxicity herb. It was concluded that W. chinensis has a definite hepatoprotective effect against liver injuries.

Hepatoprotective effects of Taiwan folk medicine: Ixeris chinensis (Thunb.) Nak. on experimental liver injuries.

The hepatoprotective effects of Ixeris chinensis (Thunb.) Nak. were studied on acute hepatitis induced in mice by a single dose of carbon tetrachloride (31.25 microliters/kg, ip) or acetaminophen (600 mg/kg, ip), and in rats by a single dose of beta-D-galactosamine (188 mg/kg, ip). Hepatoprotective activity was monitored by estimating the serum transaminases (SGOT and SGPT) levels and histopathological changes in the livers of experimental animals. The Ixeris chinensis (Thunb.) Nak. extracts significantly inhibited the acute elevation of serum transaminases. Histopathologically, the crude I. chinensis extract significantly ameliorated hepatotoxin-induced histopathological changes in the livers of experimental animals. All pharmacological and histopathological effects of Ixeris chinensis (Thunb.) Nak. were compared with Bupleurum chinense DC., which has been previously reported as a treatment herb for hepatitis.