西红柿汁抗垃圾渗滤液致紫露草微核突变的作用

目的研究垃圾渗滤液的致微核突变及西红柿对其的拮抗作用。方法选择健康有序的紫露草,分别用原液、75%原液、50%原液、25%原液上分别处理7h、15h、30h及设对照组;同时,用5%西红柿处理紫露草花粉母细胞,并设阳性与阴性对照组。结果垃圾渗滤液能显著诱发紫露草微核的形成,引起多种畸变,并呈明显的剂量效应和时间效应(P<0.01);在西红柿处理组中与对照组相比,其微核率显著降低。结论垃圾渗滤液对生物具有致微核突变的作用;适量的西红柿具有抗渗滤液的突变作用。     

盐藻β-胡萝卜素抗突变效应

目的：研究盐藻β胡萝卜素（βｃａｒｏｔｅｎｅｆｒｏｍＤｕｎａｌｉｅｌａｓａｌｉｎａ，βＣＤＳ）致突变及抗突变作用．方法：用体外人淋巴细胞微核和染色体畸变检测，研究了βＣＤＳ对γ射线和丝裂霉素（Ｍｉｔ）诱变作用的影响．结果：βＣＤＳ１－３０ｍｇ·Ｌ－１对人淋巴细胞无致突变性，但能抑制γ射线诱发的微核形成和Ｍｉｔ诱发的染色体畸变．当合成β胡萝卜素与天然β胡萝卜素油（βＣＤＳ成份之一）按８０∶２７５混合后，拮抗了前者的遗传毒性，并使两者的抗突变作用得到增强．结论：βＣＤＳ是一种抗突变成份     

几种药物抗重铬酸钾的诱变效应

以小鼠骨髓细胞微核率为指标,研究了维生素C、维生素E、亚硒酸钠、促排灵、依地酸二纳钙和二巯基丁二酸钠抗重铬酸钾的诱变效应。除二巯基丁二酸钠外,其他五种药物都使重络酸钾诱发的微核率明显降低,表明这些药物有抗重络酸钾诱变的效应。     

复方云芝胶对丝裂霉素C诱发突变及老年自发突变的抑制作用

采用体外培养人淋巴细胞微核检测法，探讨复方云芝胶囊抗突变作用。结果表明，复方云芝胶囊（１０ｍｇ／Ｌ￣５０ｍｇ／Ｌ）可显著抑制丝裂霉素Ｃ（ＭＭＣ）诱发的微核形成，并可拮抗老年人自发微核，增加细胞增殖活性。     

叶绿酸铜钠抗突变作用的实验研究

用小鼠骨髓细胞微核试验和小鼠睾丸染色体畸变试验探讨叶绿酸铜钠的抗突变作用。结果：叶绿酸铜钠能有效地抑制由环磷酰胺诱导的小鼠ＰＣＥ微核的发生;在睾丸染色体畸变试验中,表现为对环磷酰胺诱导的小鼠精母细胞染色体畸变的抑制作用,由此表明,叶绿酸铜钠是一种有效的抗突变物质。     

利用旋光化合物R—（＋）—α—甲基苄胺直接合成依托咪酯

以旋光化合物Ｒ－（＋）－α－甲基苄胺为起始原料经缩合，Ｎ、Ｃ－甲酰化，环合及脱硫直接合成依托咪酯，不需折分，工艺简便，总收率达４７％。     

xylE 转基因小鼠突变检测系统的建立

为了验证ｘｙｌＥ转基因小鼠能否用于体内基因突变检测,首先对从小鼠体内回收目的质粒的影响因素（电压,基因组ＤＮＡ浓度和Ｔ４连接酶浓度）进行了研究,结果发现用ＨｉｎｄⅢ酶切后的０．５μｇ组织ＤＮＡ在４００μＬ反应体系中以０．３ＵＴ４连接酶连接后,以１６ｋＶ,２００Ω,２５μＦ的参数用电穿孔法转化大肠杆菌ＤＨ１０Ｂ菌株是回收目的质粒效率最高的方法．在此基础上观察了致突变剂ｎ－甲基－ｎ′－硝基－ｎ－亚硝基胍（ＭＮＮＧ）对转基因小鼠（ｉｐ１０ｍｇｋｇ－１ｄ－１,连续４ｄ）外周血正染红细胞（ＮＣＥ）的微核率和肝组织中ｘｙｌＥ基因的自发和诱发突变率,并对突变的ｘｙｌＥ基因进行序列分析,结果ＭＮＮＧ使外周血ＮＣＥ的微核率从（２．２０±１．４８）‰上升为（６．８０±２．２８）‰（Ｐ＜０．０１）,ｘｙｌＥ基因的突变率从小于１／２２８４３增至４／１８６４１,表明ＭＮＮＧ可诱发转基因小鼠ＮＣＥ微核率和肝组织中ｘｙｌＥ基因突变率显著升高．序列分析显示ＭＮＮＧ诱发的ｘｙｌＥ基因突变主要是单碱基缺失．上述结果表明ｘｙｌＥ转基因小鼠是检测体内基因突变的有效模型．     

复方云芝胶囊对丝裂霉素C诱发突变及老年自发突变的抑制作用

采用体外培养人淋巴细胞微核检测法,探讨复方云芝胶囊抗突变作用。结果表明,复方云芝胶囊（１０ｍｇ／Ｌ～５０ｍｇ／Ｌ）可显著抑制丝裂霉素Ｃ（ＭＭＣ）诱发的微核形成,并可拮抗老年人自发微核,增加细胞增殖活性。     

中国软珊瑚Nephtha Crassica化学成分的研究

从采自中国南海西沙群岛的软珊瑚Ｎｅｐｔｈｅａ ｃｒａｓｓｉｃａ中分离到８种结晶物质。包括３β，７β，１９－三羟基，２４－亚甲基胆甾醇（ＮＣ－８），３β，５α，６β，１９－四羟基，２４－亚甲基胆甾醇（ＮＣ－４）。本研究首次运用二维核磁共振技术和一些别的光谱数据，推导出ＮＣ－８和ＮＣ－４的结构。     

参莲颗粒抗突变和抑瘤作用研究

目的:研究参莲颗粒的抗突变和抑瘤作用。方法:以小鼠骨髓细胞微核实验和睾丸染色体畸变实验观察参莲颗粒的抗突变作用;并观察参莲颗粒对S180和H22移植性肿瘤的抑制作用。结果:参莲颗粒对环磷酰胺诱发的小鼠骨髓细胞微核发生和丝裂霉素诱发的小鼠睾丸细胞染色体畸变均有显著的抑制效果;对S180和H22移植性肿瘤的生长有显著的抑制作用。结论:参莲颗粒对体细胞和生殖细胞的DNA损伤均有保护作用,对小鼠移植性肿瘤有较好的抑制作用。     

Sister chromatid exchanges and micronuclei formations induced by sorbic acid and sorbic acid-nitrite in vivo in mice

The in vivo induction of sister chromatid exchanges and micronuclei formations by acute treatment with different concentrations of sorbic acid and by nitrite, individually and in combination, was studied in bone marrow cells of mice. A significant increase in the frequency of sister chromatid exchanges was only observed with the three higher concentrations of sorbic acid when compared to a distilled water control. Sodium nitrite produced a significant increase at all doses tested. A combination of half the concentration of sorbic acid and of sodium nitrite gave an additive effect over that of sorbic acid or sodium nitrite alone. In the micronucleus assay, the highest dose of sorbic acid (150 mg/kg body weight) produced a significant increase in micronuclei formations compared to the distilled water control. Sodium nitrite alone induced significant numbers of micronuclei at all concentrations tested when compared to the negative control. However, a combination of half the concentration of sorbic acid and of sodium nitrite gave synergistic effects which could possibly be ascribed to the formation of certain genotoxic compounds in vivo.     

Nitric oxide donating compounds inhibit HCl-induced gastric mucosal lesions mainly via prostaglandin

Prostaglandin (PG) and nitric oxide (NO) have been known to inhibit the lesion formation induced by necrotic agents. However, no clear correlation between PG and NO has been shown in the gastroprotective action against necrotic agent-induced gastric mucosal lesions in rats. Thus, the present study was performed to clarify this correlation. Gastric mucosal lesions were induced by the oral administration of 0.6 M HCl in rats. 16,16-Dimethyl PGE2 (0.3-3 microg/kg, p.o.; dim-PGE2), sodium nitrite (0.3 and 1 mg/kg, s.c.) and sodium nitroprusside (30 and 100 microg/kg, i.v.; SNP) dose-dependently inhibited the lesion formation. Orally administered sodium nitrite or SNP (3 mg/kg) also significantly inhibited the lesion formation. The gastroprotective action by dim-PGE2 was not affected by the pre-treatment with N(G)-nitro-L-arginine methylester (10 mg/kg, i.v.). The gastroprotective effect by sodium nitrite or SNP was markedly attenuated by the pre-treatment with indomethacin (10 mg/kg, s.c.). These findings suggest that NO donating compounds inhibit the HCl-induced mucosal lesions mainly through prostaglandin, but dim-PGE2 directly inhibits the lesions without involvement of NO in rats.     

The protective potential of <Emphasis Type="Italic">Yucca schidigera</Emphasis> (Sarsaponin 30<Superscript>®</Superscript>) against nitrite-induced oxidative stress in rats

The present study was designed to determine the protective effects of Yucca schidigera (Ys) against oxidative damage induced by acute nitrite intoxication as well as the histopathological evaluation of Ys in rats. The rats were divided into three groups each containing 12 rats: control (C); nitrite intoxication (N); Ys + nitrite intoxication (NY). C and N groups were fed standard rat feed (SRF). The NY group was fed SRF + 100 ppm Ys powder for 4 weeks. Acute nitrite intoxication was induced by subcutaneous (s.c.) administration of sodium nitrite (60 mg/kg) 1 day after the feeding period. Fifty minutes after sodium nitrite administration, blood samples and tissues including lung, liver, and kidney were collected for clinical biochemistry and histopathological investigations. Ys treatment was found to decrease methemoglobin, blood and tissue malondialdehyde, and tissue nitric oxide concentrations, and to increase the glutathione in blood and various tissues. However, plasma nitric oxide, total antioxidant activity, β-carotene, and vitamin A did not differ between N and NY groups. While the N group rats showed distinct pathology in various tissues (compared with controls), the NY group had similar lung and liver pathology to the control. Only moderate or mild hemorrhage and hyperemia were seen in kidneys of NY group rats. Consequently, the natural compounds found in Ys, such as polyphenols, steroidal saponins, and other phytonutrients, could be used to substantially protect the organism from nitrite-induced oxidative damage and its complications.     

Cyanide intoxication: protection with chlorpromazine.

Protection against cyanide intoxication in mice can be enhanced by the administration of chlorpromazine, providing it is given with sodium thiosulfate, or the sodium thiosulfate-sodium nitrite antidotal combination. Protency ratios which were derived from the LD50 values were compared in groups of mice premedicated with chlorpromazine (10 mg/kg) and/or sodium thiosulfate (1 g/kg) and/or sodium nitrite (100 mg/kg). These results indicate that the administration of chlorpromazine alone provides no protection against the lethal effects of cyanide. Chlorpromazine also does not enhance the protective effect of sodium nitrite; however, it strikingly potentiates the effectiveness of sodium thiosulfate either alone or in combination with sodium nitrite.     

Sodium nitrite-induced cytotoxicity in cultured human gastric epithelial cells.

To investigate the effect of sodium nitrite on the viability of the human gastric adenocarcinoma epithelial cell line, AGS, cultured AGS cells were exposed to various concentrations of sodium nitrite for 24, 48 or 72 h. The cytotoxic response was assessed using a cell proliferation assay, and the extent of the response was evaluated on the basis of intracellular and extracellular levels of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), interleukin 8 (IL-8) and tumor necrosis factor (TNF-alpha). Both mRNA and protein levels were measured for each cytokine. Sodium nitrite had a significant effect on AGS cell proliferation after a 72-h exposure. At low sodium nitrite concentrations (up to 6.25 mM), cell proliferation increased in a dose-dependent manner; however, exposure to higher concentrations resulted in a dose-dependent decrease in cell proliferation. Sodium nitrite at a low concentration (6.25 mM) increased IL-8 release, whereas IL-1 beta, IL-6, and TNF-alpha release increased only after exposure to high sodium nitrite concentration (25 mM). Our data demonstrate that sodium nitrite can induce the release of these inflammatory cytokines and that high concentrations of sodium nitrite decrease AGS cell proliferation.     

Sodium Nitrite Prevents both Reductions in Circulating Nitric Oxide and Hypertension in 7‐Day Lead‐Treated Rats

Hypotensive effects of oral sodium nitrite have been reported as alternative sources of nitric oxide (NO) formation in animals and human beings. Reductions in NO bioavailability were observed in lead‐induced hypertension. However, no previous study has examined whether a single daily dose of sodium nitrite prevents the reductions in the NO bioavailability in lead‐induced hypertension. Then, we expanded previous reports and evaluated the effects of sodium nitrite in 7‐day lead‐treated rats. Wistar rats were divided into four experimental groups: Pb+sodium nitrite group received intraperitoneally (i.p.) 1st dose 8 µg/100 g of lead acetate and a subsequent dose of 0.1 µg/100 g, and daily treatment with sodium nitrite (45 mg/kg/day) or water (Pb group) by gavage for 7 days; Sodium nitrite group received i.p. 1st dose 8 µg/100 g of sodium acetate and a subsequent dose of 0.1 µg/100 g, and daily treatment with sodium nitrite (45 mg/kg/day) or water (saline group) by gavage for 7 days. Similar and higher whole‐blood lead levels (11.5 ± 1.2 and 13.2 ± 0.7 µg/dL) were found in lead‐exposed rats treated with either water or sodium nitrite (Pb or Pb+sodium nitrite, respectively; both p < 0.05 versus control groups). We found lower NO markers such as plasma nitrite and nitrite + nitrate (NOx) levels (both p < 0.05 versus controls) in lead‐exposed rats compared with normotensive (sodium acetate)‐treated controls (Pb group versus saline group; p < 0.05). Lead induced increases in systolic blood pressure (from 130 ± 2 to 164 ± 6 mmHg in Pb group; p < 0.05); however, both lead‐induced decreases in NO markers and hypertension (Pb+sodium nitrite group versus Pb group; both p < 0.05) were prevented by a single daily dose of sodium nitrite. In conclusion, these findings are consistent with the idea that impaired NO bioavailability contributes to the maintenance of elevated blood pressure in lead‐induced hypertension. Additionally, our results show that sodium nitrite exerts antihypertensive effects in lead‐induced hypertension and provide evidence that sodium nitrite prevents the impairment of NO, thus, reaffirming the relevance of nitrite as alternative source of recycling back to NO.     

Oxidation of cardiac myoglobin in vivo by sodium nitrite or hydroxylamine

A non-vascularized fish heart model was used to assess the oxidation of cardiac myoglobin in vivo by compounds known to cause methemoglobinemia. Buffalo sculpin (Enophrys bison) were cannulated from the afferent branchial artery to permit repeated blood sampling and injected intraperitoneally with sodium nitrite, hydroxylamine or aniline. Methemoglobin was formed by sublethal levels of sodium nitrite or hydroxylamine. For hydroxylamine, the time to peak effect was less than 1 h. For sodium nitrite, the onset was less rapid and the effect more prolonged. Aniline had no effect on hemoglobin at any concentration tested. Cardiac myoglobin, assayed at the time of peak effect on hemoglobin, was oxidized in a dosedependent manner by sodium nitrite or hydroxylamine. At high doses of sodium nitrite (50 and 100 mg/kg), the oxidation of myoglobin exceeded that of hemoglobin. The reverse was true of hydroxylamine at all concentrations tested. This study suggests the possibility that cardiac myoglobin is oxidized in occupational or other exposures to sodium nitrite, hydroxylamine and related compounds.     

Role of nitric oxide in histamine release from human basophils and rat peritoneal mast cells

The effects of a range of nitric oxide (NO)-related compounds on histamine release from human basophils and rat peritoneal mast cells were studied. Basal and immunologic histamine releases from human basophils were not affected by N(omega)-nitro-L-arginine, N(omega)-nitro-L-arginine methyl ester, aminoguanidine or methylene blue (all inhibitors of NO production), sodium nitroprusside (an NO donor), L-arginine (a substrate for NO synthase) or D-arginine (the inactive enantiomer of L-arginine). In rat peritoneal mast cells, NO donors such as sodium nitroprusside, sodium nitrite and sodium nitrate, and lipopolysaccharide (an inducer of NO synthase) had little effect on basal histamine release, while 3-morpholino-sydnonimine (SIN-1, an NO donor), L-arginine and D-arginine increased this release by up to threefold. None of the inhibitors of NO production had any striking effect on histamine release induced by anti-rat immunoglobulin E (IgE), compound 48/80, sodium fluoride, phospholipase C, 1,2-dioctanoyl-sn-glycerol or ionophore A23187. However, haemoglobin was found to inhibit histamine release by anti-rat IgE or A23187 by ca. 40%. Alone of the NO donors, low concentrations of L-arginine produced a mild inhibition of histamine release induced by anti-IgE, compound 48/80 and A23187, but not other ligands, while sodium nitroprusside dose-dependently inhibited (by a maximum of ca. 30%) histamine release by anti-rat IgE, sodium fluoride or A23187. Stimulation with a variety of secretagogues or treatment with L-arginine, D-arginine, lipopolysaccharide, SIN-1 or sodium nitroprusside had no effect on NO production. Similarly, L-arginine, D-arginine or sodium nitroprusside did not change intracellular cGMP levels. On the basis of these results, it is suggested that NO does not play a significant role in the modulation of histamine release from human basophils or rat peritoneal mast cells. The effects of L-arginine, D-arginine and sodium nitroprusside may involve mechanisms unrelated to NO.     

The inhibitory effect of 3-amino-1,2,4-triazole on relaxation induced by hydroxylamine and sodium azide but not hydrogen peroxide or glyceryl trinitrate in rat aorta.

1. In this study we investigated the role of catalase in relaxation induced by hydroxylamine, sodium azide, glyceryl trinitrate and hydrogen peroxide in isolated rings of rat aorta. 2. Hydrogen peroxide (1 microM-1 mM)-induced concentration-dependent relaxation of phenylephrine (PE)-induced tone in endothelium-containing rings. In endothelium-denuded rings, however, higher concentrations (30 microM-1 mM) of hydrogen peroxide were required to produce relaxation. The endothelium-dependent component of hydrogen peroxide-induced relaxation was abolished following pretreatment with N(O)-nitro-L-arginine methyl ester (L-NAME, 30 microM). L-NAME (30 microM) had no effect, however, on hydrogen peroxide-induced relaxation in endothelium-denuded rings. 3. Pretreatment of endothelium-denuded rings with catalase (1000 u ml-1) blocked relaxation induced by hydrogen peroxide (10 microM-1 mM). The ability of catalase to inhibit hydrogen peroxide-induced relaxation was partially blocked following incubation with 3-amino-1,2, 4-triazole (AT, 50 mM) for 30 min and completely blocked at 90 min. 4. Pretreatment of endothelium-denuded rings with methylene blue (MeB, 30 microM) inhibited relaxation induced by hydrogen peroxide (10 microM-1 mM), sodium azide (1-300 nM), hydroxylamine (1-300 nM) and glyceryl trinitrate (1-100 nM) suggesting that each acted by stimulation of soluble guanylate cyclase. 5. Pretreatment of endothelium-denuded rings with AT (1-50 mM, 90 min) to inhibit endogenous catalase blocked relaxation induced by sodium azide (1-300 nM) and hydroxylamine (1-300 nM) but had no effect on relaxation induced by hydrogen peroxide (10 microM-1 mM) or glyceryl trinitrate (1-100 nM). 6. In a cell-free system, incubation of sodium azide (10 microM-3 mM) and hydroxylamine (10 microM-30 mM) but not glyceryl trinitrate (10 microM-1 mM) with catalase (1000 u ml-1) in the presence of hydrogen peroxide (1 mM) led to production of nitrite, a major breakdown product of nitric oxide. AT (1-100 mM) inhibited, in a concentration-dependent manner, the formation of nitrite from azide in the presence of hydrogen peroxide. 7. These data suggest that metabolism by catalase plays an important role in the relaxation induced by hydroxylamine and sodium azide in isolated rings of rat aorta. Relaxation appears to be due to formation of nitric oxide and activation of soluble guanylate cyclase. In contrast, metabolism by catalase does not appear to be involved in the relaxant actions of hydrogen peroxide or glyceryl trinitrate.