DNA damage after acute and chronic treatment with malathion in rats

Malathion is an insecticide widely used in agriculture and in public health programs that when used indiscriminately in large amounts can cause environmental pollution and risk to human health. However, it is possible that during the metabolism of malathion, reactive oxygen species can be generated, and malathion may produce oxidative stress in intoxicated rats that can be responsible for alterations in DNA molecules related in some studies. As a result, the present study aimed to investigate the DNA damage of cerebral tissue and peripheral blood in rats after acute and chronic malathion exposure. We used single cell gel electrophoresis (Comet assay) to measure early damage in hippocampus and peripheral blood and the Micronucleus test in total erythrocytes samples. Malathion was administered intraperitoneally once a day for one day (acute) or for 28 days (chronic) protocols (in both protocols, malathion was administered at 25, 50, 100, and 150 mg/kg). Our results showed that malathion (100 and 150 mg/kg) increased the DNA damage index in the peripheral blood and in the hippocampus after both chronic and acute treatment. Malathion increased the frequency of micronuclei only in chronic treatment at 150 mg/kg dose, and induced a cytotoxic dose-dependent decrease in the frequency of polychromatic erythrocytes in the peripheral blood of rats. In conclusion, since malathion increased both the peripheral blood and hippocampus DNA damage index using the Comet assay and increased the frequency of micronuclei in the total peripheral blood, it can be regarded as a potential mutagen/carcinogenic agent.     

Disposition and metabolic profiling of bisphenol F in pregnant and nonpregnant rats

The distribution of bisphenol F (4,4'-dihydroxydiphenyl-methane, BPF) was studied in female Sprague-Dawley rats. Pregnant and nonpregnant animals were gavaged with a single dose of 7 or 100 mg/kg [3H]BPF and were kept for 96 h in metabolic cages. The excretion of BPF residues occurred mainly in urine (43-54% of the administered dose), which was found to contain at least six different metabolites, and to a lesser extent in feces (15-20% of the administered dose). Sulfatase treatment and subsequent high-performance liquid chromatography analyses suggest that the major urinary metabolite (more than 50% of the radioactivity present in urine) is a sulfate conjugate of BPF. At 96 h, BPF residues were detectable in all tissues examined with the largest amounts in the liver (0.5% of the dose). In pregnant rats dosed at day 17 of gestation, BPF residues were detected in the uterus, placenta, amniotic fluid, and fetuses (0.9-1.3% of the administered dose). Large amounts of radioactivity (8-10% of the dose) were still located in the digestive tract lumen at the end of the study. After administration of a single oral dose of [3H]BPF, 46% of the distributed radioactivity was excreted in bile over a 6 h period. In rats, BPF and/or its metabolites very likely undergo enterohepatic cycling, which could be responsible for the relatively high amounts of residues still excreted 4 days after BPF administration. This bisphenol is efficiently absorbed and distributed to the reproductive tract in female rats, and its residues pass the placental barrier at a late stage of gestation in rats.     

仿刺参肠多糖对免疫功能的影响及抗肿瘤研究

多糖能参与机体的免疫调节,具有抗肿瘤等多种功能。本实验采用灌胃不同剂量仿刺参(Apostichopus japonicus)肠多糖的方法,研究了多糖对小鼠(Mus musculus)免疫功能的影响及其对小鼠的抗肿瘤作用。结果显示,仿刺参肠多糖对接种的H22肿瘤具有剂量依赖性的抑制作用,高剂量组(400mg/kg/d)抑瘤效果最好;胸腺指数高剂量肿瘤组最高(P<0.05),而其他各组差异不明显,脾脏指数在肿瘤组内随着剂量的增大表现为先升高再降低,而空白组呈一直上升的趋势;高剂量多糖可以显著提高荷瘤小鼠和空白小鼠的白介素2(IL-2)含量(P<0.05),对荷瘤小鼠的肿瘤坏死因子(TNF-α)含量也具有显著提升作用(P<0.05),但对空白组小鼠的TNF-α含量影响不显著;荷瘤小鼠的自然杀伤(NK)细胞活力普遍低于空白小鼠,随灌胃剂量的提升空白小鼠NK细胞活力具有上升趋势,荷瘤小鼠的NK细胞活力在中剂量组达到最高后开始下降。实验表明,仿刺参肠多糖可以促进小鼠的免疫功能,并且对小鼠体内肿瘤在一定剂量范围内具有浓度依赖性的抑制作用。     

52-Week oral gavage chronic toxicity study with ubiquinone in rats with a 4-week recovery

Potential ubiquinone (CoQ10; a natural fermentation product) toxicity was assessed in rats administered CoQ(10) by oral gavage for 1 year at 100, 300, 600, and 1200 mg/(kg day). No adverse changes in mortality, clinical signs, body weight, food consumption, or clinical pathology results occurred. CoQ(10) had elimination half-lives ranging from 10.7 to 15.2 h. At 1200 mg/(kg day), a high incidence of orange, granular, lumenal exudate in nasal turbinates occurred; microscopically, findings similar to those in the turbinates were occasionally observed in small granulomas within lung alveoli. A dose-related increased incidence of vacuolated macrophages (mesenteric lymph nodes) and vacuolated hepatic periportal cells was noted. Neither were associated with tissue damage or organ dysfunction, so they were not considered to be adverse. The nasal turbinate and lung findings were probably secondary to incidental exposure to crystallized test material. Overall, CoQ(10) was well tolerated by male and female rats at dose levels up to 1200 mg/(kg day).     

Oxidative metabolites of the mammalian lignans enterodiol and enterolactone in rat bile and urine

Recent studies have shown that the mammalian lignans enterodiol (END) and enterolactone (ENL) are biotransformed in vitro by hepatic microsomes from rats and humans to various metabolites carrying one additional hydroxy group either at the aromatic or at the aliphatic moiety. To clarify whether these metabolites are also formed in vivo, each lignan was administered intraduodenally at a dose of 10 mg/kg of bw to bile duct-catheterized female Wistar rats and the 6 h bile analyzed by HPLC and GC-MS. With END-dosed rats, three products of aromatic and two of aliphatic monohydroxylation were found, whereas six aromatic and five aliphatic monohydroxylated biliary metabolites were detected after administration of ENL. The metabolites hydroxylated at the aromatic rings were unequivocally identified by comparison with synthetic reference compounds. The structures of the in vivo metabolites arising from aliphatic hydroxylation could not be completely elucidated; they were identical with some of the formerly reported microsomal products according to GC retention times and mass spectra. Significant amounts of most of the metabolites of the mammalian lignans identified in bile were also found in the urine of female rats after oral administration of 10 mg/kg of bw END or ENL and in the urine of female and male Wistar rats after they had been fed a diet containing 5% flaxseed. Thus, the mammalian lignans END and ENL give rise to several hydroxylated metabolites in vivo, which may contribute to the biological effects of these important food constituents.     

Anthocyanin extracted from black soybean reduces prostate weight and promotes apoptosis in the prostatic hyperplasia-induced rat model

Anthocyanin is a natural plant pigment and potent antioxidant. This study was designed to investigate the effects of anthocyanin extracted from black soybeans on a rat model of benign prostatic hyperplasia (BPH), a disease associated with the geriatric population. Thirty male rats were divided into five experimental groups: a control group, a BPH-induced group, and three BPH-induced groups that received oral doses of anthocyanin (40, 80, and 160 mg/kg). Prostate hyperplasia was induced by the administration of testosterone propionate for 4 weeks. Following BPH induction, the anthocyanin-treated groups received the compound for 4 weeks. After anthocyanin treatment, the prostates from the rats in all groups were removed, weighed, and subjected to histological examination. Apoptosis in the prostates was measured by the TUNEL assay. The mean prostate weight for the control animals was 674.17 ± 28.24 mg, whereas the BPH-induced rats had a mean prostate weight of 1098.33 ± 131.31 mg. The mean prostate weights for the rats receiving 40, 80, and 160 mg/kg anthocyanin were 323.00 ± 22.41, 324.00 ± 26.80, and 617.50 ± 31.08 mg, respectively. The average prostate weight in the BPH-induced group was significantly higher than in the control group (p < 0.05), whereas the prostate weights in the anthocyanin-administered groups were significantly lower than in the BPH-induced group (p < 0.05). Injected testosterone led to prostatic hyperplasia as observed histologically, but anthocyanin administration helped to prevent this change. Apoptotic body counts were significantly higher in groups receiving anthocyanin than in the BPH-induced group (p < 0.05). These results suggest that anthocyanin may be effective in decreasing the volume and suppressing the proliferation of the prostate. Further studies are needed to better understand the mechanisms and actions of anthocyanin, and these studies may lead to the clinical application of anthocyanin in treating BPH.     

Absorption, tissue distribution, excretion, and metabolism of clothianidin in rats

Absorption, distribution, excretion, and metabolism of clothianidin [(E)-1-(2-chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine] were investigated after a single oral administration of [nitroimino-(14)C]- or [thiazolyl-2-(14)C]clothianidin to male and female rats at a dose of 5 mg/kg of body weight (bw) (low dose) or 250 mg/kg of bw (high dose). The maximum concentration of carbon-14 in blood occurred 2 h after administration of the low oral dose for both labeled clothianidins, and then the concentration of carbon-14 in blood decreased with a half-life of 2.9-4.0 h. The orally administered carbon-14 was rapidly and extensively distributed to all tissues and organs within 2 h after administration, especially to the kidney and liver, but was rapidly and almost completely eliminated from all tissues and organs with no evidence of accumulation. The orally administered carbon-14 was almost completely excreted into urine and feces within 2 days after administration, and approximately 90% of the administered dose was excreted via urine. The major compound in excreta was clothianidin, accounting for >60% of the administered dose. The major metabolic reactions of clothianidin in rats were oxidative demethylation to form N-(2-chlorothiazol-5-ylmethyl)-N'-nitroguanidine and the cleavage of the carbon-nitrogen bond between the thiazolylmethyl moiety and the nitroguanidine moiety. The part of the molecule containing the nitroguanidine moiety was transformed mainly to N-methyl-N'-nitroguanidine, whereas the thiazol moiety was further metabolized to 2-(methylthio)thiazole-5-carboxylic acid. With the exception of the transiently delayed excretion of carbon-14 at the high-dose level, the rates of biokinetics, excretion, distribution, and metabolism of clothianidin were not markedly influenced by dose level and sex.     

Biodegradation of Monoethanolamine,Ethylene Glycol and Triethylene Glycol in Laboratory Bioreactors

The release of alkanolamines and glycols into the subsurface soils poses a potential hazard to the environment through impacted soil and groundwater. This study investigated aerobic and anaerobic biodegradability of monoethanolamine (MEA), ethylene glycol (MEG) and triethylene glycol (TEG). Significant levels of MEA (31 000 mg/kg), MEG (500 mg/kg) and TEG (2100 mg/kg) were successfully aerobically biodegraded in bioreactors. The aerobic slurry experiments suggested initial phosphate (P) limitation, as biodegradation rates increased by one order of magnitude after phosphate addition. Anaerobic decay of MEA, MEG and TEG was unaffected by P-addition. MEA, MEG and TEG degradation products such as acetate, ethanol and ammonium at about 75 000 mg/kg, 8100 mg/kg and 8800 mg/kg degraded completely and did not prevent aerobic biodegradation. This study confirms proposed biodegradation pathways of MEA, MEG, TEG and their breakdown products in natural soil and groundwater using indigenous microbes. Levels of contamination studied here are significantly higher than previously reported.     

Red mold dioscorea has greater hypolipidemic and antiatherosclerotic effect than traditional red mold rice and unfermented dioscorea in hamsters

Monascus-fermented red mold dioscorea (RMD) was proven to produce higher monacolin K levels than red mold rice (RMR) in our previous study. The goal of this study is to investigate whether the novel RMD had more hypolipidemic and antiatherosclerotic effect than traditional red mold rice. The daily dose of RMR for adults was recommended as 1 g, which corresponded to 96 mg/kg/day for hamsters. Therefore, high cholesterol diet-induced hyperlipidemic hamsters were daily administrated with a 0.5-fold (48 mg/kg/day), a 1-fold (96 mg/kg/day), or a 5-fold dose (480 mg/kg/day) of RMD for 8 weeks. Furthermore, a 1-fold dose of RMR (96 mg/kg/day) and unfermented dioscorea (96 mg/kg/day) were also respectively used to evaluate the effect of hypolipidemic and antiarteriosclerosis. The results indicated that only needing a 0.5-fold dose of RMD was able to significantly lower total cholesterol (by 13.78%, p<0.001), triglyceride (by 38.74%, p<0.01), and low-density lipoprotein cholesterol levels (by 43.11%, p<0.05) as well as maintain a high-density lipoprotein cholesterol level, as compared to the hyperlipidemic group. RMD including a higher monacolin K level and a dioscorea substrate was able to exhibit a more significant difference in the hypolipidemic effect than RMR or unfermented dioscorea. Both RMR and dioscorea exhibited potent in vitro antioxidative ability and in vivo protection against hypolipidemia-induced oxidative stress. Therefore, the antioxidative ability of RMD provided by Monascus metabolites (dimerumic acid, tannin, phenol, etc.) as well as dioscorea was able to perform more antiatherosclerotic effects on increasing total antioxidant status, catalase, and superoxide dismutase activity and repressing lipid peroxidation and atherosclerotic plaque than RMR and dioscorea.     

Behavioral responses of rats exposed to long-term dietary vinclozolin

Vinclozolin is a fungicide used on food crops with human exposure estimated at approximately 2 microg/kg/day from ingestion; occupational exposure, however, may be greater. The metabolites of vinclozolin have been reported to act as antiandrogens and have adverse effects on reproductive physiology and behavior in animals. Here, pregnant rats were fed soy-free diets containing 0, 10, 150, or 750 ppm of vinclozolin (approximately 0, 0.8, 12, and 60 mg/kg/day for an adult) beginning on gestational day 7, and offspring were continued on these diets through sacrifice at postnatal day 77. Male and female offspring were assessed for changes in several nonreproductive sexually dimorphic behaviors: open field and running wheel locomotor activity, play behavior, and consumption of saccharin- and sodium chloride-flavored solutions. There was a significant interaction of sex with vinclozolin exposure on running wheel activity, which indicated that females in the high-dose exposure group were hypoactive compared to same-sex controls. There was a significant overall effect of vinclozolin exposure on fluid consumption, and high-dose animals showed increased intake of the saccharin solution and decreased intake of plain water while saccharin was available. Effects were more pronounced in females, which drank 40.8% more saccharin than control females, whereas males drank 6.2% more than control males. There were no effects of vinclozolin treatment on play behavior or sodium solution intake. Gestational duration, total and live pups per litter, litter sex ratios, and birth weight were also not significantly affected, nor were body weight and food intake for dams and offspring. These results indicate that long-term dietary exposure to vinclozolin does not have severe toxicological consequences on the nonreproductive behaviors measured here. However, exposure may cause subtle alterations in locomotor activity and consumption of saccharin-flavored solution.     

Effects of water-soluble hemicellulose from soybean hull on serum antibody levels and activation of macrophages in rats

Effects of soybean hull water-soluble hemicellulose (WSHC) on serum immunoglobulin (Ig) concentration and production of NO and IL-1beta from peritoneal macrophages were examined and compared with those of Agaricus blazei in the rat system. WSHC consisted of arabinose, galactose, xylose, glucose, and rhamnose, and the molecular weight was approximately 500000. Rats were ip administrated each sample at a dose of 0.67, 13.4, or 26.9 mg/kg/day for 14 days. The administration of WSHC resulted in significantly higher productions of IgM (p < 0.01 on day 6, p < 0.05 on day 14) and IgG (p < 0.05 on day 6) than those in other groups. When peritoneal macrophages were stimulated with various concentrations of sample (0.67, 13.4, or 26.9 mg/mL), WSHC significantly increased both NO and IL-1beta productions only at the concentration of 13.4 (mg/mL) compared with those of a saline group. These findings demonstrate that WSHC enhances humoral immunity and activation of macrophages, thereby leading to the augmentation of immune responses in rats.     

Effects of hydroxytyrosol and hydroxytyrosol acetate administration to rats on platelet function compared to acetylsalicylic acid

Virgin olive oil (VOO) contains the polyphenols hydroxytyrosol (HT) and hydroxytyrosol acetate (HT-AC). This study investigated the antiplatelet effect of HT and HT-AC in healthy rats and compared their effects to acetylsalicylic acid (ASA). All compounds were administered orally for 7 days. HT and HT-AC inhibited platelet aggregation in whole blood, with a 50% inhibitory dose (ID50) of 48.25 mg/kg per day for HT, 16.05 mg/kg per day for HT-AC, and 2.42 mg/kg per day for ASA. Platelet synthesis of thromboxane B2 was inhibited by up to 30% by HT and 37% by HT-AC; the ID50 of this effect for ASA was 1.09 mg/kg per day. Vascular prostacyclin production was inhibited by up to 27.5% by HT and 32% by HT-AC; the ID50 of this effect for ASA was 6.75 mg/kg per day. Vascular nitric oxide production was increased by up to 34.2% by HT, 66% by HT-AC, and 64% by ASA. We conclude that HT and HT-AC administered orally inhibited platelet aggregation in rats and that a decrease in thromboxane synthesis along with an increase in nitric oxide production contributed to this effect.     

Oral administration of Trapa taiwanensis Nakai fruit skin extracts conferring hepatoprotection from CCl4-caused injury

As a folk medicine, the hot-water infusion of water caltrop fruits has been used to protect the liver. In this study, the outer skins of mature water caltrop fruits ( Trapa taiwanensis Nakai) were removed, forced-air-dried, pulverized, and subjected to extraction with hot water, and the infusion was lyophilized and pulverized to prepare a hot water extract of T. taiwanensis (HWETT). HWETT was subjected to assays of α,α-diphenyl-β-picrylhydrazyl scavenging activity, reducing power, Trolox equivalent antioxidant capacity, and antioxidative potency, and all determinations showed HWETT to be a potent antioxidant. As further analyzed with LC-MS, two major HPLC-detected components were elucidated as gallic acid and ellagic acid. Hepatoprotective activity of HWETT was assessed with Sprague-Dawley male rats by oral administration. Six groups of rats (n = 8 for each) were respectively treated, namely, control, CCl(4) (20% CCl(4)/olive oil by 2.0 mL/kg bw), CCl(4) and Silymarin (200 mg/kg bw), CCl(4) and low HWETT dose (12.5 mg/kg bw), CCl(4) and medium HWETT dose (25 mg/kg bw), and CCl(4) and high HWETT dose (125 mg/kg bw). After 8 weeks, all animals were fasted for an additional day and sacrificed to collect blood, liver, and kidney for analyses. Histopathological examinations showed that oral administrations with Silymarin and HWETT were effective in protecting the liver from CCl(4)-caused fatty change. Oral administration of HWETT at 125 mg/kg bw was more effective than was Silymarin at 200 mg/kg bw. On biochemical analyses, oral administrations with HWETT at medium and high doses were effective (p < 0.05) in lowering CCl(4)-caused increases of alanine aminotransferase and aspartate aminotransferase activities. It is of merit to demonstrate HWETT as a potent source of antioxidants and hepatoprotective agents.     

Nephrocalcinosis formation by soy isoflavones in male rats

Isoflavones (IFs), found in the form of both aglycones and glucosides in soybean foods, induce weak estrogenic activities. Although IFs have a number of health benefits, it was previously reported that IFs cause nephrocalcinosis (NC) in the kidney of male Fischer 344 (F344) rats. The present study aims to elucidate the safety of IFs by focusing on IF-induced NC formation in rats. Fermented soybean extract (FSE) containing 420 mg/g isoflavone aglycones was orally administered to male F344 and Sprague-Dawley (SD) rats for 28 days. FSE induced NC formation in the kidney of F344 rats, but not in SD rats. However, absorption of IFs did not differ between F344 and SD rats. NC formation and its severity of FSE were histologically compared with those of soybean extract (SE) containing 518 mg/g isoflavone glucosides in F344 rats. There were no differences in the number of NC formations and the extent of calcium deposit between FSE and SE groups. To examine the dose effect of FSE on NC formation, doses of 20, 140, or 1000 mg/kg FSE were administered to F344 rats for 90 days. NC formation was observed in the 140 and 1000 mg/kg groups. These results indicated that a high dose of oral administration of IFs induced NC formation depending on the strain of rat.     

Improvement of mitochondrial function in muscle of genetically obese rats after chronic supplementation with proanthocyanidins

The aim of this study was to determine the effect of chronic dietary supplementation of a grape seed proanthocyanidin extract (GSPE) at a dose of 35 mg/kg body weight on energy metabolism and mitochondrial function in the skeletal muscle of Zucker obese rats. Three groups of 10 animals each were used: lean Fa/fa lean group (LG) rats, a control fa/fa obese group (OG) of rats, and an obese supplemented fa/fa proanthocyanidins obese group (POG) of rats, which were supplemented with a dose of 35 mg GSPE/kg of body weight/day during the 68 days of experimentation. Skeletal muscle energy metabolism was evaluated by determining enzyme activities, key metabolic gene expression, and immunoblotting of oxidative phosphorylation complexes. Mitochondrial function was analyzed by high-resolution respirometry using both a glycosidic and a lipid substrate. In muscle, chronic GSPE administration decreased citrate synthase activity, the amount of oxidative phosphorylation complexes I and II, and Nrf1 gene expression, without any effects on the mitochondrial oxidative capacity. This situation was associated with lower reactive oxygen species (ROS) generation. Additionally, GSPE administration enhanced the ability to oxidize pyruvate, and it also increased the activity of enzymes involved in oxidative phosphorylation including cytochrome c oxidase. There is strong evidence to suggest that GSPE administration stimulates mitochondrial function in skeletal muscle specifically by increasing the capacity to oxidize pyruvate and contributes to reduced muscle ROS generation in obese Zucker rats.     

Protection by petaslignolide A, a major neuroprotective compound in the butanol extract of Petasites japonicus leaves, against oxidative damage in the brains of mice challenged with kainic acid

The neuroprotective effect of petaslignolide A (PA), a furfuran lignan isolated from butanol fraction of Petasites japonicus (Sieb. et Zucc.) Maxim. (Compositae) leaves, on the oxidative damage in the brain of mice challenged with kainic acid was examined using behavioral signs and biochemical parameters of oxidative stress. PA (40 mg/kg) was administered to ICR male mice through a gavage for 4 days consecutively, and on the final day, kainic acid (50 mg/kg) was administered intraperitoneally. During the 4-day treatment with PA, the body weight gain was not significantly different from that of vehicle-treated control animals. PA (40 mg/kg) alleviated the behavioral signs of kainic acid neurotoxicity and reduced the mortality (50%) by kainic acid to 12.5%. Moreover, the administration of PA restored the levels of glutathione and thiobarbituric acid-reactive substances as well as GSH-peroxidase activity in the brains of mice administered kainic acid to control levels (P < 0.05). In comparison, PA (40 mg/kg) was approximately comparable to the butanol fraction (200 mg/kg) of P. japonicus extract in reducing kainic acid neurotoxicity. On the basis of these results, PA is suggested to be a major neuroprotective agent primarily responsible for the protective action of the butanol fraction of P. japonicus extract against kainic acid-induced neurotoxicity in the brains of mice.     

Excretion of (14)C-fumonisin B(1), (14)C-hydrolyzed fumonisin B(1), and (14)C-fumonisin B(1)-fructose in rats.

14C-Fumonisin B(1) (FB(1)) was produced by Fusarium proliferatum M-5991 in modified Myro liquid medium and purified to >95% purity with a specific activity of 1.7 mCi/mmol. Nine male and nine female F344/N rats were each dosed by gavage with 0.69 micromol of (14)C-FB(1), (14)C-hydrolyzed FB(1), or (14)C-FB(1)-fructose/kg body weight. Urinary excretion of (14)C-FB(1) and (14)C-FB(1)-fructose was 0.5% and 4.4% of the total dose, respectively, and was similar between male and female rats. Urinary excretion of (14)C-hydrolyzed HFB(1) was significantly greater (P > 0.05) in female rats as compared with male rats (17.3% vs 12.8% of the total dose, respectively). There were no significant (P > 0.05) differences in biliary excretion of the three fumonisin compounds with a mean of 1. 4% of the dose excreted at 4 h after dosing. Lesser amounts continued to be excreted up to 9.25 h after dosing. Although biliary excretion of the (14)C-FB(1), (14)C-hydrolyzed FB(1), and (14)C-FB(1)-fructose was similar, increased urinary excretion of the (14)C-hydrolyzed FB(1) as compared to (14)C-FB(1) and (14)C-FB(1)-fructose indicated a greater absorption of the hydrolyzed form.     

The metabolic fate of purified glucoraphanin in F344 rats

Dietary broccoli is commonly eaten cooked, exposing individuals to intact glucoraphanin rather than to its hydrolysis product, the anticarcinogenic isothiocyanate sulforaphane, since cooking destroys the hydrolyzing enzyme myrosinase. There is little information on the absorption and metabolism of glucoraphanin, due partly to the lack of purified compound. In this study, glucoraphanin was purified from broccoli seed and 150 mumol/kg was administered to male F344 rats. Glucoraphanin (5% of an oral dose) was recovered intact in urine, showing that it is absorbed intact, and no glucoraphanin or metabolites were found in feces. Total urinary products accounted for 20 and 45% of oral and intraperitonneal doses, respectively, including sulforaphane N-acetyl cysteine conjugate (12.5 and 2%), free sulforaphane (0.65 and 0.77%), sulforaphane nitrile (2 and 1.4%), and erucin (0.1 and 0.1%), respectively. Both glucoraphanin and its reduced form glucoerucin were identified in bile following intravenous glucoraphanin administration. We conclude that orally administered glucoraphanin is absorbed intact, undergoes enterohepatic circulation, and is hydrolyzed in the gut in F344 rats.     

Neuroprotective effect of rough aster butanol fraction against oxidative stress in the brain of mice challenged with kainic acid

The neuroprotective effect of the butanol fraction from the methanol extract of Aster scaber Thunb. (rough aster butanol fraction) on oxidative damage in the brain of mice challenged with kainic acid was examined using behavioral signs and biochemical parameters of oxidative stress. The rough aster butanol fraction (0.4-1.0 g/kg) was administered to ICR male mice, 6-8 weeks, through a gavage for 4 days consecutively, and on the third day, kainic acid (50 mg/kg) was ip administered. When compared to the vehicle-treated control, no significant changes in body and brain weight were observed in mice administered the rough aster butanol fraction. Administration of kainic acid only, causing a lethality of approximately 54%, resulted in a significant decrease of total glutathione level and an increase of the thiobarbituric acid-reactive substances (TBARS) value in brain tissue. When the rough aster butanol fraction was examined for neuroprotective action, the rough aster butanol fraction (0.4 g/kg) alleviated the lethality (25%) of kainic acid and the behavioral sign of its neurotoxicity. Moreover, administration of the rough aster butanol fraction at a dose of 0.4 g/kg restored the glutathione level in the cytosolic portion of brain homogenate to approximately 80% (p < 0.05). Also, the rough aster butanol fraction (0.4 g/kg) led to a significant reduction of kainic acid-induced increase of TBARS value. In addition, the glutathione peroxidase activity was restored significantly (p < 0.05) in the cytosolic portion of brain homogenate, whereas glutathione reductase activity was not. On the basis of these results, the rough aster butanol fraction is suggested to contain a functional agent to prevent oxidative stress in the brain of mice.     

Effect of garlic oil on neutrophil infiltration in the small intestine of endotoxin-injected rats and its association with levels of soluble and cellular adhesion molecules

Garlic ( Allium sativum ) possesses anti-inflammatory effects. This study investigated the effects of garlic oil on endotoxin-induced neutrophil infiltration in the small intestine. Wistar rats received by gavage 10, 50, or 100 mg/kg body wt garlic oil (GO) or the vehicle (corn oil; 2 mL/kg body wt) every other day for 2 weeks before being injected with endotoxin (ip, 5 mg/kg body wt). Control rats were administered corn oil and injected with sterile saline. Blood samples for the measurement of soluble adhesion molecules were collected at various time points after injection, and all other samples were collected 18 h after injection. The 10 and 50 mg/kg doses suppressed endotoxin-induced neutrophilia, serum levels of sL-selectin and sICAM-1, cellular CD11b on neutrophils, intestinal ICAM-1 content, and neutrophil infiltration (P < 0.05). The 100 mg/kg dose significantly lowered local ICAM-1 and cellular CD11b on neutrophils (P < 0.05) but did not have a beneficial effect on neutrophil infiltration. In addition, 100 mg/kg of GO worsened the elevation of the local TNF-α level and neutrophilia. Appropriate doses of garlic oil have a preventive effect on endotoxin-induced neutrophil infiltration and damage to the small intestine.