Environmental laws and ecological restoration projects enhancing ecosystem services in China: A meta-analysis.

In recent decades, China has implemented ecological restoration projects (ERPs) to improve biodiversity and ecosystem services (ESs), accordingly, a series of environmental laws were issued to guide ecological restoration. However, quantitative evaluation of the effectiveness of ERPs remains ambiguous. To respond to the UN Decade on Ecosystem Restoration (UNDER), we conducted a meta-analysis of 85 peer-reviewed publications and an interdisciplinary evaluation framework based on China's environmental protection and land administration laws (EPLALs) were established to assess the effectiveness of ERPs. We found that ERPs enhanced ESs by 15-58%. Specifically, ERPs implemented in industrial/mining, and wetland regions significantly increased regulating and cultural services, and in arid and semi-arid regions mainly enhance provisioning services (72.98%). Climate factors were found to be crucial for ecological restoration effectiveness (temperature: r = -0.582, significance <0.05; precipitation: r = 0.635, significance <0.05). China's environmental laws emphasized management and investment in ecological restoration. However, the disclosure, public participation and real-time monitoring of ecological conditions need to be improved urgently. We therefore developed ERP-related policy recommendations and global lessons to help improve the effectiveness of ecological restoration.

Dam-mediated flooding impact on outpatient attendance and diarrhoea cases in northern Ghana: a mixed methods study.

BACKGROUND: Floods are the most frequently occurring natural disaster and constitute a significant public health risk. Several operational satellite-based flood detection systems quantify flooding extent, but it is unclear how far the choice of satellite-based flood product affects the findings of epidemiological studies of associated public health risks. Few studies of flooding's health impacts have used mixed methods to enrich understanding of these impacts. This study therefore aims to evaluate the relationship between two satellite-derived flood products with outpatient attendance and diarrhoeal disease in northern Ghana, identifying plausible reasons for observed relationships via qualitative interviews. METHODS: A convergent parallel mixed methods design combined an ecological time series with focus group discussions and key informant interviews. Through an ecological time series component, monthly outpatient attendance and diarrhoea case counts from health facilities in two flood-prone districts for 2016-2020 were integrated with monthly flooding map layers classified via the Moderate Resolution Imaging Spectroradiometer (MODIS) and Landsat satellite sensors. The relationship between reported diarrhoea and outpatient attendance with flooding was examined using Poisson regression, controlling for seasonality and facility catchment population. Four focus group discussions with affected community members and four key informant interviews with health professionals explored flooding's impact on healthcare delivery and access. RESULTS: Flooding detected via Landsat better predicted outpatient attendance and diarrhoea than flooding via MODIS. Outpatient attendance significantly reduced as LandSat-derived flood area per facility catchment increased (adjusted Incidence Rate Ratio = 0.78, 95% CI: 0.61-0.99, p < 0.05), whilst reported diarrhoea significantly increased with flood area per facility catchment (adjusted Incidence Rate Ratio = 4.27, 95% CI: 2.74-6.63, p < 0.001). Key informants noted how flooding affected access to health services as patients and health professionals could not reach the health facility and emergency referrals were unable to travel. CONCLUSIONS: The significant reduction in outpatient attendance during flooding suggests that flooding impairs healthcare delivery. The relationship is sensitive to the choice of satellite-derived flood product, so future studies should consider integrating multiple sources of satellite imagery for more robust exposure assessment. Health teams and communities should plan spatially targeted flood mitigation and health system adaptation strategies that explicitly address population and workforce mobility issues.

Optimizing the Use of Cultivated Land in China's Main Grain-Producing Areas from the Dual Perspective of Ecological Security and Leading-Function Zoning.

In order to achieve the coordinated development of ecological protection and cultivated land use, ecological security and cultivated land use functions (CLUFs) in the study area were evaluated by constructing a comprehensive evaluation index system. The leading CLUFs were measured, and it was determined to use the normalized revealed comparative advantage (NRCA) index. The spatial superposition analysis of the ecological security level and the leading CLUFs was carried out to obtain the zoning of the coordinated development of ecological security and cultivated land use, and differentiated utilization strategies were proposed for different zones. The results of this study showed the following: (1) The ecological security level of cultivated land in Yuanyang County can be divided into high, medium, and low security levels, accounting for 30.68%, 43.42%, and 25.9% of the total cultivated land area, respectively. The overall ecological security level is high. (2) The current cultivated land use mainly has a production function, accounting for 38.39% of the total cultivated land area, the leading CLUFs that are 34.16% of the cultivated land are the ecological function, and 27.45% of the cultivated land is the living function. (3) The spatial superposition analysis of the ecological security level and leading CLUFs yielded four zones of cultivated land use enhancement, including a production core zone, and different control strategies were proposed for the different zones. These strategies may help to fully realize the multifunctionality of the cultivated land without compromising ecological protection. Implementing differentiated protection for cultivated land in different use zones can achieve the coordinated development of ecological protection and cultivated land use, thus promoting the sustainable use of cultivated land resources.

Increased flooded area and exposure in the White Volta river basin in Western Africa, identified from multi-source remote sensing data.

Accurate information on flood extent and exposure is critical for disaster management in data-scarce, vulnerable regions, such as Sub-Saharan Africa (SSA). However, uncertainties in flood extent affect flood exposure estimates. This study developed a framework to examine the spatiotemporal pattern of floods and to assess flood exposure through utilization of satellite images, ground-based participatory mapping of flood extent, and socio-economic data. Drawing on a case study in the White Volta basin in Western Africa, our results showed that synergetic use of multi-temporal radar and optical satellite data improved flood mapping accuracy (77% overall agreement compared with participatory mapping outputs), in comparison with existing global flood datasets (43% overall agreement for the moderate-resolution imaging spectroradiometer (MODIS) Near Real-Time (NRT) Global Flood Product). Increases in flood extent were observed according to our classified product, as well as two existing global flood products. Similarly, increased flood exposure was also observed, however its estimation remains highly uncertain and sensitive to the input dataset used. Population exposure varied greatly depending on the population dataset used, while the greatest farmland and infrastructure exposure was estimated using a composite flood map derived from three products, with lower exposure estimated from each flood product individually. The study shows that there is considerable scope to develop an accurate flood mapping system in SSA and thereby improve flood exposure assessment and develop mitigation and intervention plans.

Effect of blueberry on hepatic and immunological functions in mice.

BACKGROUND: Conventional drugs used in the treatment and prevention of liver diseases often have side effects, therefore research into natural substances are of significance. This study examined the effects of blueberry on liver protection and cellular immune functions. METHODS: To determine the effects of blueberry on liver protective function, male mice were orally administered blueberry (0.6 g/10 g) or normal saline for 21 days. Hepatic RNA was extracted by Trizol reagent, and the expression of Nrf2, HO-1, and Nqo1 was determined by real-time RT-PCR. Superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenate were determined, and liver index was measured. To assess the effects of blueberry on cellular immune function, male mice received blueberry (0.4, 0.6, or 0.8 g/10 g) for 35 days, and the percentages of CD3+, CD4+, and CD8+ T lymphocyte subgroups in peripheral blood were detected by flow cytometry, the index of the thymus and spleen was measured, and lymphocyte proliferation in the spleen was determined by MTT assay. RESULTS: Blueberry treatment significantly increased the expression of Nrf2, HO-1, and Nqo1, the important antioxidant components in the liver. Hepatic SOD in the blueberry group was higher and MDA was lower than that in the control group (P<0.05). Blueberry also increased the index of the spleen and enhanced the proliferation of lymphocytes of the spleen (P<0.05). The percentages of the CD3+ and CD4+ T lymphocyte subsets and the CD4+/CD8+ ratio were also increased by blueberry (P<0.05). CONCLUSIONS: Blueberry induces expression of Nrf2, HO-1, and Nqo1, which can protect hepatocytes from oxidative stress. In addition, blueberry can modulate T-cell function in mice.

[Model establishment of liver fibrosis in oral arsenic solution exposed mice].

OBJECTIVE: To discuss and compare the model establishment of liver fibrosis in oral arsenic solution exposed mice and mice with high-fat feedstuff. METHODS: A total of 240 mice were divided randomly into 6 groups: control group, sodium arsenite group, sodium arsenate group, high-fat feedstuff group, sodium arsenite group with high-fat feedstuff and sodium arsenate group with high-fat feedstuff with 40 mice each. Control group and high-fat feedstuff group (drinking tap water), sodium arsenite group and sodium arsenite group with high-fat feedstuff (drinking 300 mg/L iAs3+ water), sodium arsenate group and sodium arsenate group with high-fat feedstuff (drinking 300 mg/L iAs5+ water). The mice were sacrificed after 3, 6, 10 months' arsenic-exposure and examined for liver function. HE dyeing and Masson dyeing were also employed to observe the pathological changes in hepatic tissue in each group. RESULTS: After 3 months' modeling, ALT and AST in control group, sodium arsenite group, sodium arsenate group, sodium arsenite group with high-fat feedstuff and sodium arsenate group with high-fat feedstuff were (36.7 +/- 5.7) U/L and (110 +/- 22) U/L, (55.6 +/- 4.6) U/L and (249 +/- 41) U/L, (52.6 +/- 8.8) U/L and (161 +/- 15) U/L, (311.3 +/- 19.7) U/L and (484 +/- 15) U/L and (515.0 +/- 60.8) U/L and (671 +/- 24) U/L. They were higher in all the arsenic groups than in control group (P < 0.05); all the HE dyeing samples in arsenic groups showed liver injury in varying degrees such as hydropic degeneration, fatty degeneration, spotty necrosis, focal necrosis and inflammatory cell infiltration. There were liver cell regeneration and fibroplasia in varying degrees. The liver injury of the mice in all arsenic groups aggravated as exposure time prolonged. Masson dyeing after 10 months' modeling showed hyperplasia in portal areas and central venous areas; the mean area of fibrosis in control group, sodium arsenite group, sodium arsenate group, sodium arsenite group with high-fat feedstuff and sodium arsenate group with high-fat feedstuff were 0.1333, 0.5584, 0.5250, 0.7534 and 0.7200 respectively. There was statistical significance between arsenic groups and control group (P < 0.05) CONCLUSION: The liver injury and fibrosis model in oral arsenic solution exposed mice and those with high-fat feedstuff are successfully established and subsequently evaluated. It is a comparatively ideal animal model for studying arsenic liver injury and fibrosis.

Spatial variation of human influences on grassland biomass on the Qinghai-Tibetan plateau.

An improved understanding of increased human influence on ecosystems is needed for predicting ecosystem processes and sustainable ecosystem management. We studied spatial variation of human influence on grassland ecosystems at two scales across the Qinghai-Tibetan Plateau (QTP), where increased human activities may have led to ecosystem degradation. At the 10 km scale, we mapped human-influenced spatial patterns based on a hypothesis that spatial patterns of biomass that could not be attributed to environmental variables were likely correlated to human activities. In part this hypothesis could be supported via a positive correlation between biomass unexplained by environmental variables and livestock density. At the 500 m scale, using distance to settlements within a radius of 8 km as a proxy of human-influence intensity, we found both negatively human-influenced areas where biomass decreased closer to settlements (regions with higher livestock density) and positively human-influenced areas where biomass increased closer to settlements (regions with lower livestock density). These results suggest complex relationships between livestock grazing and biomass, varying between spatial scales and regions. Grazing may boost biomass production across the whole QTP at the 10 km scale. However, overgrazing may reduce it near settlements at the 500 m scale. Our approach of mapping and understanding human influence on ecosystems at different scales could guide pasture management to protect grassland in vulnerable regions on the QTP and beyond.

Characterization of polymethoxyflavone demethylation during drying processes of citrus peels.

Polymethoxyflavones (PMFs) are found almost exclusively in citrus peel and have attracted much attention due to their potential health benefits. Dried citrus peel is an important ingredient for applications in food and traditional Chinese medicine. However, the structural changes of PMFs during drying processes of citrus peel remain unknown. In this study, for the first time we discovered that four major permethoxylated PMFs, i.e. sinensetin, nobiletin, heptamethoxyflavone and tangeretin, underwent demethylation at the 5-position on the A ring of their flavonoid structures to yield corresponding 5-demethylated PMFs during the drying process of citrus peel. Our results further demonstrated that the aforementioned PMF demethylation was through two mechanisms: acid hydrolysis and enzyme-mediated catalysis. PMF demethylation in citrus peels was systematically characterized during hot-air drying (HAD), vacuum-freeze drying (VFD) and sun drying (SD). The highest PMF demethylation was obtained in SD followed by HAD and VFD. This study provided a solid scientific basis for rational control of PMF demethylation in citrus peels, which could facilitate the production of high-quality citrus peel and related products.

High dietary fat exacerbates arsenic-induced liver fibrosis in mice.

Many factors could potentially affect the process of arsenic-induced liver fibrosis. The present study was undertaken to examine the effect of high fat diet on arsenic-induced liver fibrosis and preneoplastic changes. Mice were given sodium arsenite (As3+, 200 ppm) or sodium arsenate (As5+, 200 ppm) in the drinking water for 10 months, and provided a normal diet or a diet containing 20% added fat. Serum aspartate aminotransferase (AST), indicative of liver injury, was elevated in both arsenite and arsenate groups, and a high fat diet further increased these levels. Histopathology (H&E and Masson stain) showed that liver inflammation, steatosis (fatty liver), hepatocyte degeneration, and fibrosis occurred with arsenic alone, but their severity was markedly increased with the high fat diet. Total liver RNA was isolated for real-time RT-PCR analysis. Arsenic exposure increased the expression of inflammation genes, such as TNF-alpha, IL-6, iNOS, chemokines, and macrophage inflammatory protein-2. The expression of the stress-related gene heme oxygenase-1 was increased, while metallothionein-1 and GSH S-transferase-pi were decreased when arsenic was combined with the high fat diet. Expression of genes related to liver fibrosis, such as procollagen-1 and -3, SM-actin and TGF-beta, were synergistically increased in the arsenic plus high fat diet group. The expression of genes encoding matrix metalloproteinases (MMP2, MMP9) and tissue inhibitors of metalloproteinases (TIMP1, TIMP2) was also enhanced, suggestive of early oncogenic events. In general, arsenite produced more pronounced effects than arsenate. In summary, chronic inorganic arsenic exposure in mice produces liver injury, and a high fat diet markedly increases arsenic-induced hepatofibrogenesis.

The stability of three different citrus oil-in-water emulsions fabricated by spontaneous emulsification.

In this study, emulsions were prepared through spontaneous emulsification, using three different citrus oils as the oil phase and Tween 80 as the surfactant. Utilizing 4% Tween 80, three types of citrus oil emulsions were prepared with small particle size, monomodal distribution and high transmission. After 24 h, each emulsion exhibited different degrees of gravitational separation. Mandarin oil emulsions were the most unstable, showing coalescence of small droplets with an obvious cream layer formed at 9 h. Bergamot oil emulsions possessed small droplets with the best stability over 24 h, due to their relatively polar components (e.g. linalyl acetate) and water-insoluble constituents (e.g. γ-terpinene). These results suggest that the emulsifying properties and instability mechanism of citrus oil emulsions are strongly dependent on the inherent properties and composition of citrus oils. This study is significant for the development of an effective strategy to improve the stability of citrus oil-based colloidal systems.

Characterization of physical properties and electronic sensory analyses of citrus oil-based nanoemulsions.

Citrus oils and their emulsions have been widely used in food and beverage products due to their flavor, various beneficial health functions and relative high solubility for lipophilic bioactive components. However, the non-digestibility and instability has limited the application of emulsions made from a single type of citrus oil. In this study, common triacylglycerol oils (i.e. corn oil and MCT oil) and citrus oils (i.e. bergamot oil and sweet orange oil) were used in combination with different mixing ratios (triacylglycerol oil:citrus oil = 1:0, 9:1, 5:1, 3:1, 1:1 and 0:1) to produce various nanoemulsions (10% oil phase), and their physical and electronic sensory properties were systematically characterized. The results demonstrated that the mixed oil nanoemulsions were much more stable than pure citrus oil emulsions. Electronic nose, electronic eye and electronic tongue were shown to be able to provide informative evaluation of the electronic sensory of the emulsions. Data-fitting of these electronic sensory devices significantly improved the effective discrimination and accuracy of sensory evaluation of the emulsions. These results provided basis for using triacylglycerol oils and citrus oils in combination to produce nanoemulsions with superior physical and electronic sensory properties. Moreover, the electronic sensory evaluation method utilized in this study provided a useful approach for evaluation of emulsion-based food and beverage products.

[Research into methylation of p16 gene in the patients suffering from coal-burnt arsenism in Xingren County Guizhou Province].

OBJECTIVE: To probe into the situation and significance of p16 gene CPG island methylation in patients with arseniasis caused by coal-burning pollution. METHODS: DNA was extracted using the Phenol-Chloroform method from leukocytes of 51 patients suffered from coal-burnt arsenism and 52 healthy volunteers. The quantity of the DNA was determined by UV spectrophotometry. Target DNA was denatured by NaOH, then the single strand DNA was modified by sodium bisulfite, converting all unmethylated (but not the methylated) cytosines to uracil. Subsequently a nested amplification with primers specific for methylated versus unmethylated DNA was performed, and PCR products were detected by gel electrophoresis. RESULTS: Hypermethylation of the p16 CPG island was presented in 94.1% of the patients suffering from coal-burnt arsenism and in 73.1% of the healthy volunteers. There was statistical difference (P < 0.05) between them. CONCLUSIONS: Methylation of p16 gene CPG island should have important pertinence in the metabolism of coal-burnt arsenism.

Differential effects between maotai and ethanol on hepatic gene expression in mice: Possible role of metallothionein and heme oxygenase-1 induction by maotai.

Alcohol is a risk factor for liver fibrosis and hepatocellular carcinoma. On the other hand, light alcoholic beverage consumption is believed to be beneficial because of the effects of both alcohol and nonalcoholic components of the beverage. Maotai is a commonly consumed beverage in China containing 53% alcohol. Epidemiological and experimental studies show that Maotai is less toxic to the liver than ethanol alone. To examine the differential effects of Maotai and ethanol, a low dose of Maotai or an equal amount of ethanol (53%, v/v in water, 5 ml/kg) were given to male mice daily for 1 week, and hepatic RNA was extracted for microarray analysis. Approximately 10% of genes on the liver-selective custom array (588 genes) were altered following Maotai or ethanol administration, but Maotai treated livers had fewer alterations compared with ethanol alone. Real-time reverse transcription-polymerase chain reaction confirmed and extended microarray results on selected genes. An induction of metallothionein and heme oxygenase-1 occurred with Maotai, which could not be explained by alcohol consumption alone, whereas the attenuation of ethanol responsive genes such as quinone dehydrogenase, DNA-ligase 1, IGFBP1, and IL-1beta suggests less liver injury occurred with Maotai. The expression of genes related to liver fibrosis, such as cytokeratin-18, was slightly increased by the high dose of ethanol, but was unchanged in the Maotai group. In summary, gene expression analysis indicates that Maotai induces a different response than ethanol alone. The dramatic induction of metallothionein and heme oxygenase-1 with Maotai could be important adaptive responses to reduce alcoholic liver injury.

In vivo effects of Chinese herbal recipe, Danshaohuaxian, on apoptosis and proliferation of hepatic stellate cells in hepatic fibrotic rats.

AIM: To investigate the effects of Danshaohuaxian (DSHX), a Chinese herbal recipe, on the apoptosis and cell cycles of hepatic stellate cells (HSCs) in rat hepatic fibrosis and its possible mechanisms. METHODS: Seventy-six male Wistar rats were randomly divided into normal control group, hepatic fibrosis group, non-DSHX-treated group and DSHX-treated group. Except for the normal control group, rat hepatic fibrotic models were induced by subcutaneous injection of carbon tetrachloride (CCl4), drinking alcohol, giving diet of hyperlipid and hypoprotein for 8 wk. When the hepatic fibrotic models were produced, 12 rats of hepatic fibrosis group (15 rats survived, others died during the 8 wk) were sacrificed to collect blood and livers. HSCs were isolated from the other 3 rats to detect the apoptotic index (AI) and cell cycles by flow cytometry. DSHX was then given to the DSHX-treated group (1.0 g/kg, PO, daily) for 8 wk. At the same time, normal control group and non-DSHX-treated group were given normal saline for 8 wk. At end of the experiment, some rats in these three groups were sacrificed to collect blood and livers, the other rats were used for HSC isolation to detect the apoptotic index (AI) and cell cycles. Then the liver index, serum hyaluronic acid (HA) and alanine aminotransferase (ALT), degree of hepatic fibrosis, urinary excretion of hydroxyproline (Hyp) and expression of collagen types I and III (COL I and III) in these four groups were detected respectively. RESULTS: Compared with the indexes of the hepatic fibrosis group and non-DSHX-treated group, the DSHX-treated group revealed a liver index of (0.0267+/-0.0017 vs 0.0423+/-0.0044, 0.0295+/-0.0019, P<0.05), levels of serum HA (200.78+/-31.71 vs 316.17+/-78.48, 300.86+/-72.73, P<0.05) and ALT (93.13+/-5.79 vs 174.5+/-6.02, 104.75+/-6.54, P<0.01), and stage of hepatic fibrosis (1.30 vs 4.25, 2.60, P<0.01) all reduced. The urinary excretion of Hyp increased (541.09+/-73.39 vs 62.00+/-6.40, 182.44+/-30.83, P<0.01), the COL I and III expression decreased (COL I: 1.07+/-0.96 vs 4.18+/-2.26, 3.22+/-1.44, P<0.01; COL III: 1.09+/-0.58 vs 3.04+/-0.62, 2.23+/-0.58, P<0.01), the HSCs apoptotic index of HSCs (7.81+/-0.47 vs 1.63+/-0.25, 1.78+/-0.4, P<0.05) and the ratio of G0-G1 phase cells increased (94.30+/-1.33 vs 62.27+/-17.96, 50.53+/-2.25, P<0.05). The ratios of S-phase cells (3.11+/-1.27 vs 9.83+/-1.81, 11.87+/-1.9, P<0.05) and G2-M phase cells (2.58+/-0.73 vs 23.26+/-10.95, 13.60+/-1.15, P<0.01) declined. CONCLUSION: DSHX capsule shows certain therapeutic effects on hepatic fibrosis in rats and inhibits abnormal deposition of COL I and III in rat livers by promoting the apoptosis of HSCs and preventing their proliferation.

Nitric oxide prodrugs and metallochemotherapeutics: JS-K and CB-3-100 enhance arsenic and cisplatin cytolethality by increasing cellular accumulation.

Development of chemotherapeutic resistance is a major cause of pharmacologic failure in cancer treatment. One mechanism of resistance in tumor cells is the overexpression of glutathione S-transferases (GSTs) that serve two distinct roles in the development of drug resistance via the formation of glutathione conjugates with drugs for their cellular efflux, and the inhibition of the mitogen-activated protein kinase pathway. To target GST-based resistance to chemotherapeutics, a series of nitric oxide (NO)-releasing diazeniumdiolates was synthesized and shown to release NO on reaction with GST and/or glutathione. Two diazeniumdiolates, JS-K [O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] and CB-3-100 [O(2)-(2,4-dinitrophenyl) 1-[4-(N,N-diethylcarboxamido)piperazin-1-yl]diazen-1-ium-1,2-diolate], were studied on their ability in reversing arsenic and cisplatin resistance in a rat liver cell line that is tumorigenic and shows acquired tolerance to arsenic and cisplatin, with overexpression of GSTs. The enhanced cytolethality produced by the NO donors was accompanied by increased accumulation of arsenic and platinum within cells and by enhanced activation of mitogen-activated protein kinase members c-jun-NH-kinase and extracellular signal-regulated kinase. Our data indicate that JS-K and CB-3-100 are promising lead compounds for the possible development of a novel class of adjuvant chemotherapeutic agents potentially capable of reversing arsenic and cisplatin resistance in certain tumor cells.

The nitric oxide donor, V-PYRRO/NO, protects against acetaminophen-induced nephrotoxicity in mice.

The nitric oxide (NO) donor, O(2)-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), is metabolized by P450 enzymes to release NO in the liver and possibly other tissues. V-PYRRO/NO has been shown to be hepatoprotective, but little is known about its effect in the kidney, another organ rich in P450s. Thus, mice were given V-PYRRO/NO (0.4-5.4 mg/ml, 8 microl/h) before and/or after a nephrotoxic dose of acetaminophen (APAP; 600 mg/kg, i.p.) to examine its nephroprotective effects. V-PYRRO/NO administration significantly reduced APAP-induced nephrotoxicity in a dose- and time-dependent manner, as evidenced by mitigation of increased blood urea nitrogen levels and by amelioration of renal pathology, specifically interstitial congestion, proximal tubular cell degeneration and necrosis. The best protection was observed at the highest dose (5.4 mg/ml) and with V-PYRRO/NO pretreatment (4-16 h). Implanting V-PYRRO/NO pumps simultaneously with APAP also attenuated APAP nephrotoxicity. The protection is probably not due to a decreased APAP toxication metabolism, as similar depletion of renal glutathione levels was observed regardless of V-PYRRO/NO treatment. APAP-induced renal lipid peroxidation was reduced by V-PYRRO/NO, as determined by the concentrations of hydroxynonenals and malondialdehyde. In summary, this study demonstrates that the NO donor V-PYRRO/NO is effective in blocking APAP-induced nephrotoxicity in mice. The protection is probably due to multiple mechanisms involving attenuation of APAP-induced congestion and lipid peroxidation in the kidney.

The collagenolytic effects of the traditional Chinese medicine preparation, Han-Dan-Gan-Le, contribute to reversal of chemical-induced liver fibrosis in rats.

Han-Dan-Gan-Le (HDGL), a Chinese herb preparation composed of Stephaniat tetrandra, Salvia miltorrhiza, Radix paeoniae, Astragalus membranaceus, and Ginkgo biloba, has been used to treat human liver fibrosis. This study was designed to examine the therapeutic effect of HDGL on chemical-induced liver fibrosis in adult Wistar rats. Liver fibrosis was produced in rats by carbon tetrachloride (1.2 ml CCl(4)/kg, 2 times/week, after an initial dose of 5.0 ml CCl(4)/kg, sc), plus a diet of 20% fat, 0.05% cholesterol (continuous) and 30% alcohol in the drinking water ad libitum (every other day) for 8 weeks. HDGL (0.5 and 1.0 g/kg, ig, daily for 6 weeks) was administered to rats 72 hrs after the last dose of CCl(4) to examine its therapeutic effects on chemical-induced liver fibrosis. Upon pathological examination, the HDGL treatment had significantly reversed chemical-induced liver fibrosis and other hepatic lesions. Hepatic collagen accumulation induced by CCl(4) was markedly reduced by HDGL treatment, as evidenced by hepatic collagen content and by immunohistochemical analysis of type-I collagen in liver. HDGL appeared to stimulate the collagenolytic process in the liver, as a 30-50% increase in urinary excretion of hydroxyproline was observed with HDGL treatment as compared to rats only given CCl(4). In conclusion, HDGL can effectively reverse chemically induced liver fibrosis, and this appears to be due, at least in part, to the stimulation of hepatic collagenolysis, resulting in a resolution of hepatic fibrosis.

Gene array analysis of the hepatic response to endotoxin in glutathione peroxidase-deficient mice.

Glutathione peroxidase-1 (Gpx1) is a major defense enzyme against peroxides. Gpx1-deficient mice (Gpx1-/-) are more susceptible than wild-type (WT) mice to neutrophil-induced oxidant stress and liver injury produced by 700 mg/kg galactosamine and 10 microg/kg endotoxin (Gal/ET). However, it is unclear if Gal/ET modulates redox-sensitive genes in Gpx1-/- mice before the injury. Hepatic RNA was isolated 1.5 and 6 h after Gal/ET administration and subjected to gene expression analysis using Clontech customer-designed mouse toxicology array (600-gene). Gal/ET induced a significant increase in the expression of genes encoding inflammatory response, oxidative stress, growth arrest and responses to DNA damage and/or its repair. In general, more marked alterations were seen in Gpx1-/- as compared with WT mice, supporting the role of Gpx1 in cellular defense against oxidant stress to cope with aberrant gene expression. However, comparison with previous functional studies indicated that not all changes of gene expression are relevant for the pathophysiology. Thus, only a combination of gene array analysis with functional studies allows valid conclusions regarding mechanisms of cell injury.

Effect of Maotai liquor in inducing metallothioneins and on hepatic stellate cells.

AIM: To explore the possible mechanism why drinking Maotai liquor dose not cause hepatic fibrosis. METHODS: After being fed with Maotai for 56 days consecutively, the male SD rats were decollated for detecting the biological indexes, and the livers were harvested to examine the liver indexes and the level of hepatic metallothioneins (MT). Hepatic stellate cells (HSC) proliferation and collagen generation were also observed. RESULTS: Hepatic MT contents were 216.0 ng.g(-1)+/-10.8 ng.g(-1) in the rats of Maotai group and 10.0 ng.g(-1)+/-2.8 ng.g(-1) in the normal control group, which was increased obviously in Maotain group (P<0.05). In the rats with grade CCL(2) poisoning induced by Maotai, hepatic MT content was 304.8 ng.g(-1)+/-12.1 ng.g(-1) whereas in the controls with grade CCL(4) poisoning, it was 126.4 ng.g(-1)+/-4.8 ng.g(-1) (P<0.05). MDA was 102.0 nmol.g(-1)+/-3.4 nmol.g(-1) in Maotai group and 150.8 nmol.g(-1)+/-6.7 nmol.g(-1) in the control group (P<0.05). When both of the groups were suffering from grade CCL(4) poisoning, hepatic MT contents was negatively correlated with MDA (r=-0.8023, n=20, P<0.01). The 570 nmA values of each tube with HSC regeneration at concentrations of 0, 10, 50, 100, and 200 g.L(-1) of Maotai were 0.818, 0.742, 0.736, 0.72, 0.682, and 0.604, respectively. From the concentration of 10 g.L(-1), Maotai began to show obvious inhibitory effects against HSC, and the inhibition was concentration-dependent (P<0.05, P<0.01). Type I collagen contents in HSC were 61.4, 59.9, 50.1, 49.2, 48.7, 34.4 microg.g(-1) at concentrations of 0, 10, 50, 100, and 200 g.L(-1) of Maotai. At the concentration of 100-200 g.L(-1), Maotai had obvious inhibitory effect against the secretion of type I collagen (P<0.05). Gene expression analysis was conducted on cells with Maotai concentrations of 0, 50, 100g.L(-1) respectively and the ash values of beta-actin gene expression were 0.88, 0.74, and 0.59, respectively,suggesting that at the concentration of 100g.L(-1), Maotai could obviously inhibit gene expression of type I procollagen (P<0.05), but the effect was not obvious at the concentration of 50 g.L(-1) (P>0.05). At the concentration of 10 g.L(-1), HSC growth in vitro inhibition rates were 16.4+/-2.3 in Maotai group and -8.4+/-2.3 in the control group (P<0.05). CONCLUSION: Maotai liquor can increase metallothioneins in the liver and inhibit the activation of HSC and the synthesis of collagen in many aspects, which might be the mechanism that Maotai liquor interferes in the hepatic fibrosis.

Epidemiological and histopathological study of relevance of Guizhou Maotai liquor and liver diseases.

AIM: To explore the relevance of Maotai liquor and liver diseases. METHODS: Epidemiological study was conducted on groups of subjects, each consisting of 3 subjects from the Maotai liquor group consisting of 99 individuals and one from the non-alcoholic control group consisting of 33 individuals. Liver biopsy was performed on 23 volunteers from Guizhou Maotai Distillery who had a constant and long history of drinking Maotai liquor. Experimental histopathological study was conducted as follows: sixty male Wistar rats were divided into 3 groups randomly and fed with Maotai liquor, ordinary white wine, and physiological saline respectively for a period of 8 and 12 weeks. The rats were sacrificed in batches, then serum ALT, AST, TBil, and AKP were measured. Rat livers were harvested to measure the liver indexes, GSH, and MDA. Histopathological examinations were also performed. Another eighty mice were randomly divided into 4 groups and fed with Maotai (at different dosages of 10 ml.kg(-1) and 20 ml.kg(-1)), ethanol, and physiological saline. The animals were sacrificed after 4 weeks and serum ALT was determined. Then the livers were harvested and liver indexes and MDA were measured. RESULTS: The incidence rate of hepatic symptoms, splenomegaly, liver function impairment, reversal of Albumin/Globulin and increased diameter of portal veins in the Maotai liquor group were 1.0% 1/99 , 1.0% 1/99 , 1.0% 1/99 , 1.0% 1/99 , 0 0/99 and 0 0/99 , 0 0/99 ,0 0/99 , 0 0/99 , 0 0/99 , respectively. There was no significant difference between the Maotai group and the non-alcoholic control group P>0.05 . Various degree of fatty infiltration of hepatocytes was found in the 23 volunteers receiving liver biopsy, but there was no obvious hepatic fibrosis or cirrhosis. A comparison was made between the Maotai liquor group and the ordinary white wine group. It was found that hepatic MDA in rats and mice were 0.33+/-0.10 and 0.49+/-0.23 respectively in Maotai group and 0.61+/-0.22 and 0.66+/-0.32 in the ordinary white wine group; MDA had an obvious decrease in the Maotai liquor group (P<0.05); hepatic GSH were 0.12 mg.g(-1)+/-0.06 mg.g(-1) in rats of the Maotai liquor group and (0.08+/-0.02)mg.g(-1) in white wine group, it was obviously increased in the Maotai liquor group (P<0.05). After the 20 rats had been fed with ordinary white wine for 8 weeks consecutively, disarranged hepatocyte cords, fatty infiltration of hepatocytes, and fibrous septa of varying widths due to hepatic connective tissues proliferation were observed; after 12 weeks, the fibrous tissue proliferation continued and early cirrhosis appeared. Compared with the ordinary white wine group, fatty infiltration was observed in the 8-week and 12-week groups, but no necrosis or fibrosis or cirrhosis was found in the Maotai liquor group (P<0.05). CONCLUSION: Maotai liquor may cause fatty liver but not hepatic fibrosis or cirrhosis, and it can strengthen lipid peroxidation in the liver.