The effects of selenium on GPX4-mediated lipid peroxidation and apoptosis in germ cells

Emerging evidence suggests that selenium plays an essential role in sperm maturation. However, the specific signaling pathway by which selenium exerts effect has not been elucidated. To evaluate the effect of selenium on GPX4-mediated lipid peroxidation and apoptosis in germ cells, selenium deficiency was modeled by culturing GC2-spd cells in serum-free medium. Treatment with 0.5-μM sodium selenite (NaSe) or 5.0-μM selenomethionine (SeMet) significantly improved the proliferation rate and GPX4 protein expression after selenium deficiency. Moreover, NaSe and SeMet decreased the MDA content and lipid peroxidation. When adenovirus was used to knockdown the expression of the GPX4 gene (shRNA-GPX4), the early apoptosis rate of the shRNA-GPX4 cells was significantly higher than that of the EGFP cells. Increased expression of Caspase3 and Bax, as well as MDA content were observed in the shRNA-GPX4 cells compared with EGFP cells. In further, overexpression of the GPX4 gene (ORF-GPX4) cells exhibited increased cell proliferation and decreased MDA content. However, there was no significant difference in 12/15-lox expression both in ORF-GPX4 cells and shRNA-GPX4 cells. Conclusively, GPX4 was involved in the regulation of lipid peroxidation and apoptosis in GC2-spd cells. Selenium played a role in promoting cell proliferation by mediating GPX4. The regulation of GPX4 may occur independently of 12/15-Lox. These findings confirmed the effect of selenium on spermatogenesis and offered a potential target for treating abnormal semen quality in men.     

Alcoholic myopathy: lack of effect of zinc supplementation.

A chronic form of myopathy has been described in alcoholics, characterized by atrophy of type II fibers, due both to reduced protein synthesis and increased protein breakdown. Increased production of reactive oxygen species could probably play a role in increased protein breakdown. In addition, treatment with zinc might be beneficial, since it acts as a cofactor of several enzymes involved in the synthesis of proteins and antioxidants as copper-zinc-superoxidedismutase (SOD) and selenium dependent glutathione peroxidase (GPX). Based on these facts, we analyze the relative and combined effects of ethanol, protein malnutrition and treatment with zinc, 227 mg/l in form of zinc sulphate, on muscle changes in 8 groups of adult Sprague-Dawley rats fed following the Lieber-de Carli model during 5 weeks. We also study the association between muscle histological changes and the activity of GPX, SOD and lipid peroxidation products (MDA), with hormones such as IGF-1, and with trace elements involved in antioxidant systems and/or in lipid peroxidation, such as selenium, copper, zinc, and iron. We found type IIa and IIb fiber atrophy in the alcoholic animals, especially in the low-protein fed ones. This effect was mainly due to protein deficiency. Zinc played no role at all. Muscle iron increased in ethanol, low protein fed rats, either with or without zinc, and was directly related with muscle MDA levels, which in turn were related with muscle atrophy, as was also found for serum IGF-1 levels. Ethanol was the main responsible for all these changes, although protein undernutrition also played an independent role in MDA levels. A positive interaction between ethanol and protein deficiency on serum IGF-1 was also detected. These results suggest that both protein deficiency and ethanol contribute to muscle atrophy observed in alcoholized rats; this atrophy is associated with increased lipid peroxidation and muscle iron overload. Treatment with zinc sulphate confers no benefit.     

穿心莲内酯对大鼠非酒精性脂肪肝炎的防治作用

目的研究穿心莲内酯对非酒精性脂肪性肝炎大鼠（Nonalcoholic steatohepatitis,NASH）的防治作用。方法SD大鼠40只,雌雄各半,随机分为对照组、模型组、异甘草酸镁组（Magnesium isoglycyrrhizinate,MgIG）（10mg·kg^-1）及穿心莲内酯组（andrographolide,AGH）（100mg·kg^-1）。除对照组给予生理盐水外,其余各组每天上午给予脂肪乳剂灌胃;每天下午除给生理盐水外,其它组分别腹腔注射相应药物。3周后处死动物,测定血清甘油三酯（TG）、总胆固醇（TC）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、丙二醛（MDA）、超氧化物歧化酶（SOD）、肿瘤坏死因子-α（TNF-α）和肝匀浆TG、TC、MDA、SOD,并行肝脏病理学检查。结果模型组大鼠出现NASH,MgIG组及AGH组血清和肝脏TG、MDA、TNF—α均显著降低,肝组织SOD活性明显降低;肝脂肪变性和炎症程度明显减轻。结论穿心莲内酯对脂肪乳剂诱导的NASH大鼠具有防治作用。     

The effects of zinc deficiency and supplementation on lipid peroxidation in bone tissue of ovariectomized rats

This study aims at investigating how zinc deficiency and zinc application affect lipid peroxidation in bone tissue of ovariectomized rats. The study included 40 adult female rats of Sprague-Dawley species. Group 1 (n = 10): control group were fed with normal diet. Group 2 (n = 10): the group fed with normal diet after being ovariectomized. Group 3 (n = 10): the group fed with zinc-deficient diet for 6 weeks after ovariectomy. Group 4 (n = 10): the group which was given intraperitoneal zinc (3 mg/kg day zinc) in addition to normal diet for 6 weeks after ovariectomy. Malondialdehyde (MDA) and glutathione (GSH) levels were determined in erythrocyte, plasma and bone tissue. Group 3 had the highest plasma MDA levels compared to Groups 1, 2 and 4 (P < 0.05). These values were higher in Group 2 than in Groups 1 and 4 (P < 0.05). Bone and plasma MDA levels in Groups 1 and 4 were not different. Bone and erythrocyte GSH levels in Group 4 were higher than those in all other groups (P < 0.05). The lowest levels of bone and erythrocyte GSH levels were observed in Group 3 (P < 0.05). These values were higher in Group 2 when compared to those in Groups 1 and 3 (P < 0.05). This study demonstrate that zinc deficiency increased bone tissue damage in ovariectomized rats and that zinc supplementation prevented this damage.     

Role of Oxidative Stress in the Selective Toxicity of Dieldrin in the Mouse Liver

Dieldrin, an organochlorine insecticide, induces hepatic tumors in mice but not in rats. Although the mechanism(s) responsible for this species specificity is not fully understood, accumulating evidence indicates that oxidative stress may be involved. This study examined the association of dieldrin-induced hepatic DNA synthesis with the modulation of biomarkers of oxidative damage to lipids (malondialdehyde [MDA]) and DNA (8-hydroxy-2-deoxyguanosine [oh8dG]), in male B6C3F1 mice and F344 rats fed dieldrin (0.1, 1.0, or 10 mg/kg diet) for 7, 14, 28, and 90 days. The nonenzymatic components of the antioxidant defense system (ascorbic acid, glutathione, and α-tocopherol) were also examined. Increased urinary MDA was observed in mice fed 0.1, 1.0, or 10 mg dieldrin/kg diet for 7, 14, 28, and 90 days; while increased hepatic MDA was seen only after 7 days in mice fed 0.1, 1.0, or 10 mg dieldrin/kg diet and after 14 days in mice fed 10 mg/kg diet. In rats, dieldrin had no effect on either hepatic MDA or urine MDA levels after 7, 14, and 28 days of treatment. A dose-dependent increase in urinary MDA was observed in rats at the 90-day sampling time. The only significant elevation in urinary or hepatic oh8dG content was limited to urinary oh8dG in mice fed 10 mg/kg dieldrin diet for 14 days. Dietary dieldrin produced sustained decreases in hepatic and serum α-tocopherol and sustained elevations in hepatic ascorbic acid in both mice and rats. Rats, however, possessed a three- to four-fold higher content of endogenous or basal (control) hepatic α-tocopherol; and, even when fed 10 mg dieldrin/kg diet, the levels of hepatic α-tocopherol were maintained at higher levels than those of mice fed control diet. In both rats and mice fed dieldrin, transient (14 and 28 days on diet) elevations in hepatic glutathione were observed. These data support the hypothesis that the species specificity of dieldrin-induced hepatotoxicity may be related to dieldrin's ability to induce oxidative stress in the liver of mice, but not in rats. Only in mice fed dieldrin was a temporal association of increases in hepatic MDA content and hepatic DNA synthesis seen, suggesting that oxidative damage (shown by increased lipid peroxidation) may be involved in early events in dieldrin-induced hepatocarcinogenesis. Rats may be protected from dieldrin-induced oxidative stress by a more effective antioxidant defense system, characterized by higher basal levels of hepatic α-tocopherol and ascorbic acid than that seen in the mouse.     

大鼠实验性高脂血症和高脂血症性脂肪肝模型研究

目的　建立高脂血症和高脂血症性脂肪肝实验动物模型。方法　采用SD大鼠 30只 ,随机分为对照组 (n =10 )和模型组 (n =2 0 )。对照组喂普通饲料 ,模型组喂普通饲料并给予脂肪乳剂灌胃 (10ml·kg-1)。动态观察一般情况和血清TG、TC、ALT、AST、MDA、SOD和肝脏TG、TC、MDA、SOD的变化 ,并行病理检查。结果　 1wk后 ,模型组血清TG和TC明显高于正常组 ,形成了高脂血症模型。 2wk后 ,随机处死模型中的 10只 ,与正常组相比 ,发现血清TG、TC、ALT和肝脏MDA均明显升高 ,而肝脏SOD则明显降低 ,病理显示有 2只轻度脂肪变性。在第 3wk处死剩余动物 ,发现肝指数、血清脂质、ALT、AST、MDA和肝脏TG、MDA与对照组相比显著升高 ,而SOD则明显降低 ;光镜下所见模型组均出现弥漫性肝细胞脂肪变性 ,并有炎症病灶。结论　通过 1wk脂肪乳剂的喂养 ,形成了高脂血症模型 ;继续给予脂肪乳剂 ,2wk后形成高脂血症性脂肪肝模型。     

Apricot attenuates oxidative stress and modulates of Bax,Bcl-2, caspases,NFκ-B,AP-1, CREB expression of rats bearing DMBA-induced liver damage and treated with a combination of radiotherapy

We evaluated the ability of apricot to attenuate apoptosis and oxidative stress developed during the process of 7,12-dimethylbenz[a]anthracene (DMBA) and radiotherapy in the liver of rats bearing liver damage. Fifty female Wistar rats were divided into 7 groups; (i) normal control rats; (ii) rats fed with standard diet with apricot (20%), (ii) rats fed with standard diet and administrated 6 gray radiotherapy with Co 60 device applied to a single fraction, (iv) rats fed with standard diet and administered intraperitoneally DMBA (20 mg/kg), (v) rats fed with standard diet and administered DMBA and 6 gray radiotherapy, (vi) rats fed with standard rat diet and administered DMBA and supplemented apricot, (vii) rats fed with standard diet supplemented apricot administered DMBA and radiotherapy (RT) for 6 weeks. Expression of Bax, caspase 3, and glutathione activity decreased in the liver but liver expression of NF-κB, AP-1, CREB, Bcl-2 and ALT, AST, 5′NT, MDA, NO levels increased in DMBA-induced liver damage rats. In conclusion, the results suggest that apricot supplementation and irradiation given in combination, offer maximum protection against DMBA-induced hepatic carcinogenesis.     

豹皮樟总黄酮对大鼠非酒精性脂肪性肝炎的防治作用

目的研究豹皮樟总黄酮(TFLC)对大鼠非酒精性脂肪性肝炎(NASH)的防治作用。方法SD大鼠48只,随机分为6组(n=8):对照组、模型组、烟酸组及TFLC组(50、100、200 mg.kg-1)。除对照组外,其余各组每天给予脂肪乳剂和相应药物。实验开始后3 d收集72 h的粪便,测定粪便中脂质;于1 wk后断尾取血,测定血清脂质;3 wk后处死动物,测定血清甘油三酯(TG)、总胆固醇(TC)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、丙二醛(MDA)、超氧化物歧化酶(SOD)和肝匀浆TG、TC、MDA、SOD,并行肝脏病理学检查。结果模型组大鼠出现NASH,烟酸组及TFLC组(100、200 mg.kg-1)均能降低血清和肝脏TG,肝脂肪变性程度和炎症均明显减轻;TFLC组(200 mg.kg-1)还能降低血清和肝MDA,提高肝组织SOD活性。结论TFLC可以降低大鼠血和肝组织TG,且能改善NASH大鼠脂肪变,减轻炎症反应。其机制可能是:TFLC抑制TG在肠道的吸收,同时减轻脂质过氧化。     

护肝宁片治疗非酒精性脂肪性肝炎的实验研究

目的探讨护肝宁片对大鼠非酒精性脂肪性肝炎的治疗作用及机制。方法雄性SD大鼠39只,正常喂养1周后按体质量层次随机分为正常对照组（n=9）和实验组（n=30）,正常对照组予标准饮食,实验组予高脂饮食。11周末验证造模成功后,将余下25只实验组大鼠再分为：高脂组、饮食治疗组,及护肝宁高剂量组、中剂量组、低剂量组。分别给予高剂量、中剂量、低剂量护肝宁片灌胃及标准饮食。16周末处死大鼠,检测肝指数、体脂比、血清ALT、AST、TC、TG、LDL．C、血糖、超氧化物歧化酶（SOD）、丙二醛,并行肝组织病理检查及肝匀浆TC,TG,LDL—C和丙二醛测定。结果护肝宁中剂量组、护肝宁低剂量组体脂比[分别为（3．08±0．49）％与（3．07±0．82）％]较饮食治疗组及高脂组降低（P〈0．05）;护肝宁高剂量组血清AST水平、TC水平、血糖水平及肝匀浆11c水平[分别为（119．8±14．7）U／L、（1．59±0．38）mmo]／L、（5．44±0．44）mmol／L及（0．34±0．07）mmol／L]明显低于饮食治疗组,护肝宁高剂量组血清SOD水平[（47．38±5．72）％]明显高于饮食治疗组（P〈0．05）;护肝宁高剂量组较饮食治疗组及高脂组肝组织的脂肪变程度、炎症程度和纤维化程度均明显减轻（P〈0．05）。结论护肝宁片可有效治疗大鼠非酒精性脂肪性肝炎。     

Protein deficiency and muscle damage in carbon tetrachloride induced liver cirrhosis

Protein undernutrition, alterations of hormones such as IGF-1, testosterone and cortisol, and increased lipid peroxidation—which may be related with deranged metabolism of some elements such as iron (Fe), zinc (Zn), manganese (Mn), selenium (Se) or copper (Cu)—may contribute to muscle damage in non alcoholic cirrhosis. Here, we analyse the effect of protein deficiency on muscle Cu, Fe, Zn, Mn and Se in carbon-tetrachloride (CCl₄) induced liver cirrhosis. We also study the association between protein undernutrition and these trace elements with the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and lipid peroxidation products, and how all these are related with muscle morphological changes in 40 male adult Sprague-Dawley rats. Liver cirrhosis was induced by intraperitoneal injection of CCl₄ to 10 rats fed a 2% protein diet, and to another 10 fed a 18% protein control diet. Two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. After sacrifice (6 weeks later), we found type IIa fibre atrophy in the cirrhotic animals, especially in the low-protein fed ones and this was due to protein deficiency. Muscle Fe increased in low protein fed cirrhotic rats. No relationship was found between muscle changes and any of the hormones, enzymes and trace elements analysed, or with liver fibrosis. These results suggest that muscle atrophy observed in CCl₄-induced cirrhosis is related with protein deficiency, but not with cirrhosis itself.     

大豆异黄酮对2型糖尿病大鼠血清中SOD MDA GSH及NO的影响

目的研究大豆异黄酮对2型糖尿病大鼠血清中超氧化物歧化酶(SOD)、丙二醛(MDA)、还原型谷胱甘肽(GSH)及一氧化氮(NO)的影响。方法以高脂饲料喂养后的雄性SD大鼠腹腔注射小剂量链脲佐菌素(STZ)诱导2型糖尿病模型。将实验动物随机分为普食对照组、糖尿病对照组、大豆异黄酮250mg/kg、50mg/kg剂量干预组。检测各组喂养6周、10周的血糖水平,检测第10周后大鼠血清中SOD、MDA、GSH及NO的变化。结果与糖尿病对照组相比,大豆异黄酮250mg/kg剂量干预组大鼠血清中的SOD明显升高(P<0.05),MDA与NO明显下降(P<0.05);大豆异黄酮50mg/kg剂量干预组大鼠血清中GSH明显升高(P<0.05)。结论大豆异黄酮能改善2型糖尿病大鼠的抗氧化能力。     

生长期膳食缺锌小鼠肾细胞凋亡及机制研究

目的 观察膳食缺锌条件下生长期小鼠肾细胞凋亡情况、 氧化应激情况及凋亡相关因子 Bcl-2 和 Bax 的表达变化, 探讨锌缺乏诱发肾细胞凋亡的机制。方法 将刚断乳雄性小白鼠 30 只随机分为缺锌组和足锌组, 每组15 只。缺锌组喂饲缺锌饲料(0.85 mg/kg), 足锌组喂饲足锌饲料 （30 mg/kg）。应用 TUNEL 法观察小鼠肾细胞凋亡情况, 计算凋亡指数; 分别应用黄嘌呤氧化酶法和硫代巴比妥酸法测定肾超氧化物歧化酶 （SOD） 和丙二醛(MDA)含量;应用蛋白印迹技术检测肾组织中 Bcl-2、 Bax 蛋白表达变化。结果 与足锌组比较, 缺锌组小鼠肾可见 TUNEL 阳性细胞增多, 细胞凋亡指数明显增加; 抗氧化酶 SOD 活性下降, MDA 增加, 氧化应激反应增强; 凋亡相关因子 Bcl-2 蛋白表达量明显下降, Bax 蛋白表达量明显上调, Bcl-2/Bax 比值下降。结论 生长期膳食缺锌导致肾细胞抗氧化酶活性降低, 氧化应激反应增强及细胞凋亡相关因子 Bcl-2和 Bax 蛋白表达改变, 最终导致肾细胞发生凋亡。     

银杏叶提取物对局灶性脑缺血再灌注后线粒体损伤的保护作用

目的研究杏花雨注射液对大鼠局灶性脑缺血再灌注后脑线粒体中SOD、ATPase、MDA的影响，探讨其抗脑缺血作用的机制。方法雄性SD大鼠63只，随机分为9组（n=7）。假手术组、4个缺血对照组（缺血2h分别再灌注0．5、1、2、4h组，其中缺血2h再灌注4h设为模型组），3个杏花雨注射液（A）治疗组（高、中、低剂量组），金纳多注射液（B）治疗对照组。治疗组分别于术后立即舌下静脉注射A5、10、20mg／kg，B10mg／kg。测定脑线粒体中SOD、ATPase活性和MDA含量、基质游离钙浓度。结果局灶性脑缺血再灌注后脑线粒体中MDA含量、基质游离钙浓度明显升高（P〈0．01），SOD、ATPase活性明显下降（P〈0．01）；A与B均能明显提高脑线粒体中SOD、ATPase活性（P〈0．01），减少MDA、游离钙（P〈0．01）；两种注射液同等剂量差异无显著意义（P〉0．05）。结论局灶性脑缺血再灌注后线粒体钙超载，自由基生成增加。杏花雨注射液可提高缺血再灌注大鼠脑线粒体总抗氧化活力，降低MDA、游离钙含量，保护缺血再灌注引起的神经元损伤。     

Acute and subchronic toxicological evaluation of Mequindox in Wistar rats

We studied an acute and subchronic oral toxicity of Mequindox (MEQ), a quinoxaline 1,4-dioxide antimicrobial promoter, in Wistar rats according to OECD guidelines. For acute toxicity study, single doses of MEQ at 175, 550 and 2000 mg/kg b.w. were administered to rats by oral gavage. The calculated LD₅₀ was 550 mg/kg b.w. In subchronic study, rats were fed diets containing 0, 55, 110 or 275 mg MEQ/kg. There was a reduction in body weight of rats fed 275 mg MEQ/kg diet. At 90 days autopsy, a significant decrease in the kidney weight was observed in males while an increase in relative liver and adrenal weights were observed in females fed 275 mg MEQ/kg diet. There was a significant increased in alanineaminotransferase (ALT) and malondialdehyde (MDA) concentrations in males, superoxide dismutase (SOD) activities in females, and aspartateaminotransferase (AST) levels in serum of both genders fed 275 mg MEQ/kg diet. Other toxic effects of 275 mg MEQ/kg diet included significant decrease in sodium and significant increase in potassium concentrations in serum in both genders. We may conclude that MEQ can induce hepatic and adrenal histological changes as well as leaking of different serum constituents in Wistar rats.     

大蒜素对高脂饮食诱发大鼠非酒精性脂肪肝的保护作用

目的：观察大蒜素对大鼠非酒精性脂肪肝（NAFLD）的保护作用,并初步探讨相关机制。方法：SD大鼠50只,随机平均分成5组,每组10只：正常组、模型组、大蒜素高、中、低剂量组（30、20、10 mg/kg）。实验12周后观察各组大鼠肝功能酶学、血浆内毒素的含量、肝组织中血清丙二醛（MDA）含量、过氧化物歧化酶（SOD）活性、肝组织谷胱甘肽（GSH）含量、脂质代谢、血清游离脂肪酸（FFA）等水平,以及病理组织学的特点。结果：大蒜素高、中、低剂量组大鼠血脂和血浆内毒素水平与模型组相比差异均有统计学意义（P〈0.01或P〈0.05） ,各用药组大鼠血清SOD活性、MDA含量和FFA水平,以及肝组织SOD活性、MDA含量、GSH含量与模型组相比差异均有统计学意义（P〈0.01或P〈0.05） ,组织学观察表明高、中剂量大蒜素均能明显减轻肝细胞脂肪变性（P〈0.05）。结论：大蒜素对大鼠NAFLD具有很好的保护作用,并有一定的量效关系,其机制可能与对抗脂质过氧化反应和降低血浆内毒素水平有关。     

Sex differences in biochemical manifestations of selenium deficiency in rat liver with special reference to heme metabolism

In addition to its well-known effect on glutathione peroxidase, selenium deficiency causes: (1) a defect in hepatic heme metabolism characterized by a phenobarbital-mediated increase in microsomal heme oxygenase activity, and (2) an increase in hepatic glutathione S-transferase activity. Since these effects were reported in selenium-deficient male rats, and since female rats have a lower selenium requirement than males, we examined whether these effects were sex-dependent. Weanling male rats, female rats, castrated male rats, and testosterone-treated female rats were fed either a selenium-deficient or a control diet. After 8 weeks, selenium-dependent hepatic glutathione peroxidase activity was 1 per cent of respective control values in each of the selenium-deficient groups. Hepatic glutathione,S-transferase activity was doubled by selenium deficiency in normal, unoperated males but was unaffected in the other groups. In control diet fed rats phenobarbital given as a single injection caused either no significant change or a decrease in the activity of hepatic microsomal heme oxygenase, the rate-limiting enzyme in heme degradation. In contrast, microsomal heme oxygenase activity was stimulated by phenobarbital in all selenium-deficient rats. The stimulation was greatest in males and least in females with intermediate values in castrated males and testosterone-treated females. These results demonstrate a marked effect of sex, castration of males, and testosterone treatment of females on the response of hepatic heme metabolism to phenobarbital and on glutathione S-transferase activity in selenium deficiency even though glutathione peroxidase was reduced to the same extent by selenium deficiency in all groups.     

Dynamic oxidative stress and DNA damage induced by oestrogen deficiency and protective effects of puerarin and 17β-oestradiol in ovariectomized rats

Oxidative stress plays an essential role in the pathogenesis of cardiovascular diseases and osteoporosis resulting from oestrogen deficiency in the postmenopausal period. In this report, we observed a dynamic change of oxidative stress and DNA damage after ovariectomy in female rats. We then compared phytoestrogen puerarin and 17β‐oestradiol (E₂) in their effects on oestrogen deficiency‐induced oxidative stress and DNA damage. Serum total antioxidant capacity (TAC), malondialdehyde (MDA) and lymphocytes DNA damage (comet%) were measured. There was a gradual increase in oxidative stress in the ovariectomized (OVX) rats over time after ovariectomy, as compared to rats receiving sham operation. OVX rats that were on puerarin and E₂ showed increased TAC and decreased MDA in the serum, as well as decreased lymphocytes comet%. Puerarin appeared to have a more powerful protective effect on DNA oxidative damage than E₂. The study indicates that postmenopausal women may benefit from phytoestrogen puerarin.     

High nitrate intake impairs liver functions and morphology in rats; protective effects of α-tocopherol

The aim of this study was to determine the effect of high dose nitrate ingested in drinking water, on liver enzymes and histopathology, liver weight/body weight (lw/bw) ratio, serum and liver malondialdehyde (MDA) levels and osmotic fragility in Sprague-Dawley rats. These parameters were compared on 40 rats divided into four groups; control animals (group A) drank filtered tap water containing maximum 10mg/L nitrate while treatment groups drank 200mg/L (group B), 400mg/L (group C) and α-tocopherol plus 400mg/L (group D) nitrate containing water ad libitum for 60 days. As a result, lw/bw ratio increased significantly (p<0.05) among rats that consumed water with 400mg/L nitrate. Osmotic fragility increased significantly in treatment groups (p<0.05 versus control). Liver but not serum MDA levels increased in group C (p<0.05 versus control). Group A showed normal hepatic lobular architecture and histology. After nitrate administration, there was hepatocellular degeneration with increased intercellular space of the liver cells in groups B and C. Liver MDA, osmotic fragility and liver histology have returned to nearly normal in group D. These findings show clearly that high nitrate ingestion can cause pathological changes in liver histology and functions. Moreover, α-tocopherol can prevent these effects, possibly through antioxidant properties.     

Effects of maternal vitamin B6 deficiency and over-supplementation on DNA damage and oxidative stress in rat dams and their offspring

Vitamin B₆ is a cofactor for more than 140 essential enzymes and plays an important role in maternal health and fetal development. The goal of this study was to investigate the effects of maternal vitamin B₆ on DNA damage and oxidative stress status in rat dams and their offspring. Female Wistar rats were randomly assigned to three dietary groups fed a standard diet (control diet), a diet supplemented with 30 mg/kg of vitamin B₆, or a deficient diet (0 mg/kg of vitamin B₆) for 10 weeks before and during mating, pregnancy and lactation. The dams were euthanized at weaning, and their male pups were euthanized either 10 days or 100 days after birth. We found that maternal vitamin B₆ deficiency increased the micronucleus frequency in peripheral blood and bone marrow cells and also increased the concentration of hepatic TBARS (thiobarbituric acid reactive substances) in newborn pups (10 days old). In conclusion, maternal 5- to 6-fold over-supplementation of vitamin B₆ had no adverse effects, however its deficiency may induce chromosomal damage and hepatic lipid peroxidation in the offspring.     

选择性线粒体分裂抑制剂对大鼠急性脊髓损伤后神经细胞的保护作用及其机制

【摘要】目的 检测选择性线粒体分裂抑制剂-1（Mdivi-1）对大鼠急性脊髓损伤（ASCI）后神经细胞线粒体中丙二醛（MDA）、谷胱甘肽（GSH）、细胞色素C（Cyt-C）及神经细胞凋亡的影响。方法成年雌性SD大鼠36只,体质量 250~300g,随机分为假手术组（Sham组）、单纯脊髓损伤组（SCI组）、Mdivi-1预处理组（1.20mg/kg,Mdivi-1组）,各12 只。Sham组只暴露脊髓,不打击。SCI组和Mdivi-1组采用Allen’s方法制备脊髓损伤模型。Mdivi-1组在脊髓打击之前15min尾静脉给予Mdivi-1,而SCI组给予等量二甲基亚砜（DMSO）。Sham组在暴露脊髓8h后立即处死,SCI组和Mdivi-1组均于脊髓损伤后8h处死;然后取出脊髓节段T9~T11,用分光光度计检测各组脊髓组织线粒体中MDA 和GSH的含量,Western Blot法检测线粒体及胞浆内Cyt-C表达情况,荧光TUNEL法观察神经细胞凋亡情况。结果与Sham组相比,SCI组线粒体中Cyt-C和GSH明显减少,但线粒体中的MDA,胞浆中Cyt-C及神经细胞凋亡数目明显增多（P<0.01）;与SCI组相比,Mdivi-1组线粒体中Cyt-C和GSH明显增多,但线粒体中MDA,胞浆中Cyt-C以及神经细胞凋亡数目明显减少（P<0.01）。结论Mdivi-1具有减轻ASCI后神经细胞线粒体氧化损伤,抑制线粒体中Cyt-C 的释放及神经细胞凋亡的作用,促进了脊髓功能恢复。