关木通对大鼠的急性肾毒性作用的初步研究

关木通是一味常用中药,具有清热利湿功用,但关木通含有马兜铃酸,对肾脏有较强的毒性,用量过大,可引起急性肾功能衰竭,甚至死亡。本实验通过对SD大鼠灌胃关木通,观察到了不同剂量的关木通对大鼠的肾脏毒性的作用及大鼠肾脏组织形态学特点,并为此后的近一步毒性实验的剂量的设置提供依据。     

小檗碱对2型糖尿病大鼠肾组织PPARα/δ/γ表达的影响

目的:观察2型糖尿痛大鼠肾组织PPARα/δ/γ蛋白的表达及小檗碱对它们的影响.方法:小剂量注射链脲菌素(35 mg·kg-1,ip)加高糖高脂饲料饲养16周建立2型糖尿病大鼠模型,随后16周每天分别给予低中高剂量小檗碱75、150、300mg·kg-1、非诺贝特100mg·kg1 和罗格列酮4mg·kg-1,处死大鼠后用免疫组化技术检测肾脏组织中PPARα/δ/γ的表达.结果:糖尿病大鼠肾脏中PPARα和PPARδ蛋白表较正常对照大鼠明显降低(P＜0.01),PPARγ表达则较正常对照大鼠明显升高(P＜0.01).中高剂量小檗碱和非诺贝特都能促进糖尿病大鼠肾组织中PPARα和PPARδ的表达(P＜0.01),中高剂量小檗碱和罗格列酮能明显降低PPARγ表达(P＜0.01).结论:糖尿病大鼠肾脏组织中PPARα/δ/γ的表达失常,小檗碱能恢复其表达至接近正常大鼠水平.     

石菖蒲不同部位对戊四唑点燃大鼠神经肽Y含量的影响

目的:研究石菖蒲不同部位对戊四唑点燃癫痫模型大鼠神经肽Y含量的影响.方法:SD大鼠80只,腹腔注射戊四唑(PTZ)溶液35mg·kg1体重,隔天1次,共14次.点燃成功的大鼠,分8组,每天灌胃1次,分别给予石菖蒲挥发油50mg·kg-1体重、石菖蒲去油水提液高剂量28g·kg-1体重、中剂量14·kg-1体重、低剂量7g·kg-1体重、β-细辛醚100mg·kg-1体重、α-细辛醚70mg·kg-1体重,阳性对照组给予丙戊酸钠(VPA)126mg·kg-1体重治疗,模型组给予同量生理盐水.另设正常组5只,正常喂养,不作任何处理.治疗36天后注射同剂量戊四唑点燃测试药效,断头取脑,分取海马用放免法测定神经肤Y(NPY)含量.结果:与正常组比较,治疗后造模的各组大鼠海马神经肽Y含量升高,石菖蒲去油水提液低剂量组、阳性组有统计学意义(P<0.01),模型组与正常组比较有统计学意义(P<0.05).结论:治疗后造模各组大鼠海马神经肤Y含量升高,起抗癫痫作用.     

硫酸软骨素对慢性酒精中毒氧化损伤的保护作用(英文)

目的:研究硫酸软骨素对慢性酒精中毒氧化损伤的保护作用。方法:60只Wistar大鼠随机分成六个组:空白组给予蒸馏水,酒精模型组给予50%的酒精8ml·kg-1·d-1灌胃,纳洛酮组在给予酒精三十分钟后腹腔注射纳洛酮0.08mgkg-1·d-1,硫酸软骨素低、中、高剂量组在酒精模型组的基础上分别给予硫酸软骨素50,100和150mg·kg-·1d-1。两周后酒精的剂量增加到12mg·kg-1d-1。在第八周末,分离大鼠脑组织,观察大鼠神经细胞。用生物方法测定大鼠脑组织中GSH-PX、SOD、MDA以及Ache的活性。结果:模型组大鼠大脑皮质和海马区神经细胞的数量明显减少并且排列紊乱;和酒精模型组相比较,硫酸软骨素中剂量组大脑皮质和海马区神经细胞排列较整齐,酒精+Chondroitin组脑组织中MDA的含量和Ache降低(P<0.01),GSH-PX的含量和SOD的活力均明显增加(P<0.01)。结论:硫酸软骨素对慢性酒精中毒氧化损伤具有保护作用。     

藏药小檗皮对糖尿病模型小鼠血糖水平影响的初步研究

目的:观察藏药小檗皮对糖尿病小鼠模型及正常小鼠血糖的影响,并以血糖为指标确定其治疗糖尿病及其并发症的有效剂量范围.方法:以6.72 9·kg-1、3.36 9·kg-1、1.68 g·kg-1、0.84 9·kg-1、0.42 g.· kg-1剂量的小檗皮浸膏灌胃四氧嘧啶糖尿病小鼠10d,GOD-CE-PAP法测定小鼠血糖水平,以确定小檗皮的有效降糖剂量范围;6.72 g·kg-1、1.68 g·kg-1、0.84 g·kg-1剂量的小檗皮浸膏灌胃正常小鼠7d,GOD-CE-PAP法测定小鼠血糖水平,观察小檗皮对正常小鼠血糖的影响.结果:与模型对照组相比,盐酸二甲双胍、盐酸小檗碱、生物碱复配及6.72 g·kg-1、1.68 9·k-1、0.84 9·kg-1、3.36 g·kg-1、0.42 g·kg-1的小檗皮浸膏均有较好的降糖作用,5个剂量的小檗皮浸膏降糖作用依次为:6.72 9·kg-1＞ 1.689·kg-1＞ 0.849·kg-1＞3.36 g·kg-1＞0.429·kg-1;盐酸二甲双胍、羟苯磺酸钙、盐酸小檗碱、复配生物碱及6.72 9·kg-1、1.68 g·kg-1、0.849·kg-1剂量的小檗皮浸膏对正常小鼠血糖无明显作用.结论:藏药小檗皮对四氧嘧啶所致糖尿病模型小鼠血糖有明显降糖作用,对正常小鼠血糖无明显作用.     

硫酸软骨素对慢性酒精中毒氧化损伤的保护作用

目的:研究硫酸软骨素时慢性酒精中毒氧化损伤的保护作用.方法:60只Wistar大鼠随机分成六个组:空白组给予蒸馏水,酒精模型组给予50%的酒精8 ml·kg-1·d-1灌胃,纳洛酮组在给予酒精三十分钟后腹腔注射纳洛酮0.08mgkg-1·d-1,硫酸软骨素低、中、高剂量组在酒精模型组的基础上分别给予硫酸软骨素50,100和150mg·kg-1·d-1.两周后酒精的剂量增加到12mg·kg-1d-1.在第八周末,分离大鼠脑组织,观察大鼠神经细胞.用生物方法测定大鼠脑组织中GSH-PX、SOD、MDA以及Ache的活性.结果:模型组大鼠大脑皮质和海马区神经细胞的数量明显减少并且排列紊乱;和酒精模型组相比较,硫酸软骨素中剂量组大脑皮质和海马区神经细胞排列较整齐,酒精+Chondroitin组脑组织中MDA的含量和Ache降低(P＜0.01),GSH-PX的含量和SOD的活力均明显增加(P＜0.01).结论:硫酸软骨素时慢性酒精中毒氧化损伤具有保护作用.     

孕期大鼠暴露PFOS对胎鼠肝脏毒性的影响

目的:研究在孕期暴露PFOS对胎鼠的肝脏毒性的影响.方法:将孕期为12天的16只SD雌性大鼠,随机分为4组给予不同剂量的PFOS[0(对照),5,10,20 mg·kg-1],连续灌胃7天,在GD19天时对母鼠和胎鼠的体重、胎鼠肝脏的生化指标、母鼠血清的生化指标进行了相应的检测.结果:与对照组相比,母鼠体重在20 mg·kg-1组显著下降(P＜0.001);胎鼠的体重和体长在20mg·kg-1组显著下降(P＜0.001);胎鼠的肝脏重量降低,呈剂量依赖性,并伴有肝细胞浊肿、变性甚至坏死;10 mg· kg-1组胎鼠肝脏中的酶活性(ALT、AST、GGT和ALP等)显著升高(P＜0.001);母鼠血清的大部分生化指标未发生明显变化.结论:孕期大鼠暴露在PFOS的环境下会严重损伤胎鼠的肝脏功能.     

三聚氰胺泌尿系统结石大鼠模型的研究

目的观察工业原料三聚氰胺连续给药诱发SD大鼠尿结石的成模情况。方法60日龄SPF级SD大鼠130只,雌雄各半,体质量（200＋24）g,随机分为给药5个组和空白对照组各20只,溶媒对照组10只。给药组分别给予三聚氰胺0．05、0．1、0．2、0．3、0．4g／（kg·d）连续灌胃;溶媒对照组灌胃10g／L甲基纤维素蒸馏水2mL／（只·d）,空白对照组灌胃无菌水2mL/（只·d）。采用体视显微镜观察大鼠肾脏、输尿管和膀胱形态改变,比较各组肾脏、膀胱的质量和脏器指数,观察大鼠CREA、BUN、UA、Ca、P、Mg含量变化。结果0．4g／kg组给药20d,0．2、0．4g／kg组给药30d,肌酐高于空白对照组;0．4g/kg组给药30d,尿素氮、尿酸高于空白对照组。给药20d各组血钙、磷、镁均偏低。给药30d,0．05、0．2、0．3、0．4g／kg组左肾质量比空白对照组增加。各组肾脏大小、颜色均与正常对照组比较接近,未见结石和明显黄色沉淀物,但有部份肾脏在皮、髓质交界处有点状或片状出血灶。输尿管未见结石。部分膀胱粘膜充血,部分雄性大鼠出现膀胱结石,其中给药20d各组雄性大鼠出现率为52％（13／25）,30d各组出现率为56％（14／25）,膀胱结石颜色多为淡黄色混合白色、白色。结论（0．05～0．4）g/kg三聚氰胺连续给药30d,对肾脏损害轻微,可诱发雄性大鼠产生膀胱结石。     

苯污染对大鼠脑组织环核苷酸与相关蛋白水平的影响

为了探索苯污染对人类健康损伤作用的因素,选用SPF级Wistar大鼠为实验对象,分为4组:低剂量组灌胃苯0.19 g·kg-1,中剂量组灌胃苯0.38 g·kg-1,高剂量组灌胃苯0.76 g·kg-1,对照组灌胃菜籽油2 mL·kg-1;用酶联免疫吸附法(ELISA)检测脑组织中环核苷酸和相关蛋白的水平.结果发现,连...     

硫酸软骨素对慢性酒精中毒大鼠脑损伤的保护作用

目的:探讨硫酸软骨素对慢性酒精中毒脑损伤的作用及可能机制.方法:雄性 Wistar 大鼠60只随机分为6组,酒精模型组以剂量为8ml·kg-1·d-150%的酒精每天灌胃一次,纳洛酮药物组给予乙醇半小时后腹腔注射纳洛酮0.08mg·k-1·d-1,硫酸软骨素低、中、高剂量干预组在酒精模型组的基础上分别给予硫酸软骨素50、100、150mg·kg-1·d-1,空白对照组给予等体积的蒸馏水,持续2周;第三周把50%的酒精的剂量递增为12mg·kg-1·d-1,持续灌胃6周.在第八周末实验结束后取血,分离血清,留取脑组织.HE染色观察各组大鼠神经细胞的变化.生化测定各组大鼠血清及脑组织匀浆中谷胱甘肽过氧化物酶(GSH-PX)和超氧化物歧化酶(SOD)的活性以及脂质过氧物终未产物丙二醛(MDA);并测定脑皮质中β-内啡肽含量(β-EP).结果:模型组大鼠大脑皮质和海马区神经元数量明显减少,神经细胞排列紊乱.硫酸软骨素中剂量组大鼠大脑皮质和海马区神经细胞排列层次较清晰.与酒精组相比较,硫酸软骨素中剂量组大鼠血清和脑组织匀浆中MDA含量明显降低(P<0.01),脑皮质中β-内啡肽含量明显降低(P<0.01);GSH-PX含量及SOD活性显著升高(P<0.01).结论:硫酸软骨素对大鼠慢性酒精中毒脑损伤具有保护作用.     

Protection against diethylnitrosoamine-induced hepatocarcinogenesis by an indigenous medicine comprised of Nigella sativa, Hemidesmus indicus and Smilax glabra: a preliminary study

BACKGROUND: A decoction comprised of Nigella sativa seeds, Hemidesmus indicus root and Smilax glabra rhizome is used to treat cancer patients in Sri Lanka. However, the anti-carcinogenic properties of this decoction have not been experimentally confirmed. The purpose of this study was to determine whether the above decoction could protect against chemically induce hepatocarcinogenesis. METHODS: The effects of this decoction on diethylnitrosamine (DEN) induced hepatocarcinogenesis were examined in male Wistar rats using the medium term bioassay system of Ito, based on a 2-step model of hepatocarcinogenesis. Rats were randomly divided into 6 groups of 10 each. Groups 1 to 4 were injected with DEN (200 mg/kg) to initiate carcinogenesis. Twenty-four hours later groups 1 and 2 were administered the decoction at 4 g/kg body weight/day (dose 1) and 6 g/kg body weight/day (dose 2), respectively. Group 3 and group 4 were given distilled water instead of the decoction and a suspension of garlic powder (20 g/kg body weight/day) in distilled water (positive control), respectively. Group 5 and 6 were injected with normal saline and twenty-four hours later group 5 was given distilled water (normal control) while group 6 was given decoction dose 2 (decoction control). Oral feeding continued for two weeks after which all rats were subjected to 2/3 partial hepatectomy to promote carcinogenesis. Oral feeding continued for eight more weeks. At the end of the 10th week, rats were sacrificed and samples of livers taken for immunohistochemical studies.Carcinogenic potential was scored by comparing the number, area and staining intensity of glutathione S-transferase placental form (GST-P) positive foci and the number of cells/cm2 of the positive foci in the livers of the six groups of rats. RESULTS: The number and area of DEN-mediated GST-P positive foci, number of cells/cm2 of foci and staining intensity of the foci were significantly (P > 0.001) reduced by the decoction and garlic in the order dose 2 = garlic >dose 1. CONCLUSION: Overall results indicate that the decoction comprised of N. sativa, S. glabra and H. indicus has the potential to protect rat liver against DEN induced hepatocarcinogenesis     

达格列净对2型糖尿病大鼠肾脏葡萄糖转运蛋白2及葡萄糖转运蛋白4基因表达的影响*

目的:探讨达格列净对2型糖尿病大鼠肾脏葡萄糖转运蛋白2(GLUT2)和葡萄糖转运蛋白4(GLUT4)基因表达的影响。方法:使用高脂饲料和一次性注射40 mg/kg链脲佐菌素(STZ)建立2型糖尿病大鼠模型,造模大鼠以空腹血糖(FBG)含量≥16.7 mmol/L时视为造模成功。造模成功后随机分为模型组(B组,生理盐水)、达格列净低剂量组(C组,0.75 mg/kg)、达格列净中剂量组(D组,1.5 mg/kg)、达格列净高剂量组(E组,3.0 mg/kg),每组6只;另选取6只健康的SD大鼠作为正常对照组(A组,生理盐水)。各组均为灌胃给药,每天1次,连续7周。灌胃给药7周后测定大鼠的体重以及血清FBG、糖化血红蛋白(HbA1c)、血尿素氮(BUN)、血肌酐(Scr)的变化;采用酶联免疫吸附测定血清及肾组织丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px);采用HE观察肾脏病理学变化;采用Western blot检测肾脏组织中GLUT2、GLUT4蛋白表达;RT-qPCR检测肾脏组织中GLUT2、GLUT4 mRNA相对表达量。结果: 与A组比较,各组大鼠的体重及SOD、GSH-PX水平明显降低(P＜ 0.05),FBG、HbA1c、BUN、Scr、MDA水平明显升高(P＜0.05),肾脏病理损伤严重,肾组织GLUT2、GLUT4 mRNA相对表达量和蛋白表达均明显降低(P均＜0.05)。与B组比较,C组、D组和E组大鼠的体重、SOD、GSH-PX水平和肾组织GLUT2、GLUT4 mRNA相对表达量明显升高(P＜0.05),FBG、HbA1c、BUN、Scr、MDA水平明显降低(P＜ 0.05);D组和E组肾脏病理损伤明显减轻,肾组织GLUT2、GLUT4蛋白表达均明显升高(P均＜0.05)。结论:达格列净可缓解2型糖尿病模型大鼠的病情,并上调肾脏GLUT2及GLUT4基因的表达。     

Melatonin attenuates methotrexate‐induced oxidative stress and renal damage in rats

Nephrotoxicity is an adverse side effect of methotrexate (MTX) chemotherapy. The present study verifies whether melatonin, an endogenous antioxidant prevents MTX‐induced renal damage. Adult rats were administered 7 mg/kg body weight MTX intraperitoneally for 3 days. In the melatonin pretreated rats, 40 mg/ kg body weight melatonin was administered daily intraperitoneally 1 h before the administration of MTX. The rats were killed 12 h after the final dose of MTX/vehicle. The kidneys were used for light microscopic and biochemical studies. The markers of oxidative stress were measured along with the activities of the antioxidant enzymes and myeloperoxidase activity in the kidney homogenates. Pretreatment with melatonin reduced MTX induced renal damage both histologically and biochemically as revealed by normal plasma creatinine levels. Melatonin pretreatment reduced MTX induced oxidative stress, alteration in the activity of antioxidant enzymes as well as elevation in myeloperoxidase activity. The results suggest that melatonin has the potential to reduce MTX induced oxidative stress, neutrophil infiltration as well as renal damage. As melatonin is an endogenous antioxidant and is non‐toxic even in high doses it is suggested that melatonin may be beneficial in minimizing MTX induced renal damage in humans. Copyright © 2010 John Wiley & Sons, Ltd.     

Effect of crude sulphated polysaccharide from brown algae against acetaminophen-induced toxicity in rats

This study was conducted to examine the protective role of crude polysaccharide from brown seaweed Sargassum polycystum against acetaminophen-induced abnormality in blood glucose, serum albumin/globulin ratio, and liver glycogen, lactate, and pyruvate. Liver and renal tissue histology was performed to confirm the efficacy of Sargassum polysaccharide. A toxic dose of acetaminophen (800 mg/kg body weight intraperitoneally) induced severe abnormality in all basic parameters with apparent toxicity in liver (enlargement of hepatocytes, loss of cytoplasmic content with disruption in the hepatic plates and sinusoidal dilation) and renal tissue (glomerular damage with congestion of tubules). The isolated liver cells were stained with acridine orange and examined under fluorescence microscope, which revealed that the acetaminophen induced significant damage. In contrast, the rats pretreated with Sargassum polysaccharide (200 mg/kg body weight) daily for 3 weeks did not show liver and renal tissue with these severe aberrations induced by acetaminophen. Histology results were also consistent with analyzed basic biochemical parameters, which confirmed the effectiveness of the crude polysaccharide against acetaminophen-induced abnormality in rats.     

Dose-dependent effect of galangin on fructose-mediated insulin resistance and oxidative events in rat kidney

Galangin is an antioxidant flavonol present in high concentrations in the rhizome of Alpinia galanga. We investigated the effect of galangin on whole-body insulin resistance and kidney oxidative stress in a fructose-induced rat model of metabolic syndrome. Male albino Wistar rats were divided into 6 groups containing six animals each. Groups I and VI received a starch-based control diet, while groups II, III, IV and V were fed a high fructose diet (60 g/100 g). Groups III, IV and V additionally received galangin (50, 100 and 200 μg/kg body weight, respectively) while group VI received 200 μg galangin/kg body weight. At the end of 60 days, fructose-fed rats exhibited insulin resistance, increased levels of peroxidation end products and diminished antioxidant status. galangin, dose-dependently normalized blood glucose and insulin levels. The minimum effective dose was 100 μg galangin/kg body weight. At this dose, galangin also prevented the development of insulin resistance and the exaggerated the response to oral glucose challenge. The oxidant-antioxidant balance was maintained by galangin. Micro-albuminuria and tubular and glomerular changes observed in fructose-treated rats were significantly prevented by galangin (100 μg/kg body weight). These findings imply that galangin potentiates insulin sensitivity and antioxidant capacity and reduces renal damage in this dietary model of metabolic syndrome.     

海藻溴酚化合物对糖尿病大鼠抗氧化水平的影响

目的:本研究通过建立糖尿病大鼠动物模型,观察海藻溴酚化合物A、B对糖尿病大鼠机体抗氧化水平的影响。方法:采用STZ注射法制作糖尿病(DM)大鼠模型,随机分为空白对照组、糖尿病模型组、化合物A低剂量组及高剂量组、化合物B低剂量组及高剂量组,灌胃给药12周。12周末处死大鼠,测肾匀浆中谷胱甘肽过氧物酶(GSH-Px)的活力及丙二醛(MDA)的含量;并采用透射电镜观察大鼠肾组织的病理改变。结果:与空白对照组相比,糖尿病模型组肾组织匀浆中GSH-Px活力下降,MDA含量升高,差异有统计学意义(P<0.05)。各干预组中GSH-Px的活力较糖尿病模型组有升高的趋势,MDA含量有下降趋势。电镜下各干预组肾小球及肾小管病变较糖尿病组减轻,且高剂量组优于低剂量组。结论:溴酚化合物A、B能提高糖尿病大鼠机体抗氧化水平,并能一定程度的改善肾脏病理改化,但其具体机制有待进一步探讨。     

Isogenic mesenchymal stem cells transplantation improves a rat model of chronic aristolochic acid nephropathy via upregulation of hepatic growth factor and downregulation of transforming growth factor β1

Chronic aristolochic acid (AA) nephropathy (CAAN) caused by intake of AA-containing herbs is difficult to treat. We evaluated the therapeutic effect of bone marrow (BM) mesenchymal stem cells (MSCs) on a rat model of CAAN. Female Wistar rats were fed with decoction of Caulis Aristolochia manshuriensis by intragastric administration. MSCs were prepared from BM of male Wistar rats and injected into female CAAN rats through tail vein. Body weight, renal function, and urinary excretion of these CAAN rats were monitored before killing at the end of the 20th week. Blood, urine, and tissue samples were collected from experimental (MSC and non-MSC) and normal control groups. All animals developed renal fibrosis after 12 weeks of intake of AA-containing decoction. Fibrosis in the MSC groups was significantly reduced as examined with light and electron microscopy. Blood urea nitrogen, serum creatinine, and urine protein levels were significantly reduced and hemoglobin levels were improved in the MSC group as compared with the non-MSC group (p < 0.01). The expression of TGF-β1 mRNA and protein was reduced but hepatic growth factor (HGF) was increased in the MSC group compared with the non-MSC group, but still higher than the normal control level as measured by immunochemical, RT-PCR, and western blotting assays (p < 0.01). The renal fibrosis of CAAN could be protected by isogenic MSC transplantation, probably via upregulation of HGF and downregulation of TGF-β1.     

Dose-dependent effect of galangin on fructose-mediated insulin resistance and oxidative events in rat kidney

Abstract

Galangin is an antioxidant flavonol present in high concentrations in the rhizome of Alpinia galanga. We investigated the effect of galangin on whole-body insulin resistance and kidney oxidative stress in a fructose-induced rat model of metabolic syndrome. Male albino Wistar rats were divided into 6 groups containing six animals each. Groups I and VI received a starch-based control diet, while groups II, III, IV and V were fed a high fructose diet (60 g/100 g). Groups III, IV and V additionally received galangin (50, 100 and 200 μg/kg body weight, respectively) while group VI received 200 μg galangin/kg body weight. At the end of 60 days, fructose-fed rats exhibited insulin resistance, increased levels of peroxidation end products and diminished antioxidant status. galangin, dose-dependently normalized blood glucose and insulin levels. The minimum effective dose was 100 μg galangin/kg body weight. At this dose, galangin also prevented the development of insulin resistance and the exaggerated the response to oral glucose challenge. The oxidant–antioxidant balance was maintained by galangin. Micro-albuminuria and tubular and glomerular changes observed in fructose-treated rats were significantly prevented by galangin (100 μg/kg body weight). These findings imply that galangin potentiates insulin sensitivity and antioxidant capacity and reduces renal damage in this dietary model of metabolic syndrome.     

Antioxidant effects of Emblica officinalis and Zingiber officinalis on arsenic and lead induced toxicity on Albino rats

It is of interest to document the effect of Emblica officinalis (E. officinalis) and Zingiber officinalae (Z. officinalae) leaf extract on reactive oxygen species, antioxidant potential changes in arsenic and lead-induced toxicity in male rats. We used 8 groups of adult male Wistar rats with 1 control group for this study. The animals were divided into Group I: Control and Group II: Lead and sodium arsenite induced rats (animals were induced for metal toxicity by the combined administration of arsenic (13.8 mg/ kg body weight) and lead (116.4 mg/kg body weight). These doses were administered by gastric intubation during 14 consecutive days using known standard procedures. Arsenic and lead induced rats treated with ethanolic extract of Emblica officinalis (60 mg/kg body weight/day, orally for 45 days) are group III rats. Group IV animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis (120 mg/kg body weight/day for 45 days). Group V animals are arsenic and lead induced rats treated orally with ethanolic extracts of Z. officinalae (60 mg/kg body weight/day for 45 days). Group VI animals are arsenic and lead induced rats orally treated with ethanolic extracts of Zingiber officinalis (120 mg/kg body weight/day for 45 days). Group VII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (60 + 60 mg/kg body weight/day for 45 days). Group VIII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day, orally for 45 days). Normal Control animals were treated orally with ethanolic extracts of E. officinalis (120mg/kg body weight) + Z. officinalae (120mg/kg body weight) for 45 days. The control and experimental animals were then subjected to analysis for oxidative stress markers such as H2O2, *OH, and lipid peroxidation (LPO), antioxidant enzymes in addition to liver and kidney function markers. Results: Arsenic and lead induced rats showed a significant increase in the levels of reactive oxygen species (H2O2, OH* and LPO) with concomitant alterations in the renal and liver tissues. However, enzymic and non-enzymic antioxidant levels were decreased. Nevertheless, an oral effective dose of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day increased the antioxidant enzymes and retrieved the altered levels of ROS and LPO that were induced by arsenic and lead. Thus, we show that E. officinalis and Z. officinalae leaf extract exhibits nephroprotective and hepatoprotective role through the restoration of reactive oxygen species and antioxidant enzymes in the kidney and liver tissue of Arsenic and Lead-induced nephrotoxicity and hepatotoxicity in rats. Hence, E. officinalis and Z. officinalae leaf extract are potential therapeutic options for the treatment of metal toxicity-induced kidney and liver diseases.     

Dietary supplementation of vitamin A, C and E prevents p-dimethylaminoazobenzene induced hepatic DNA damage in rats

The preventive effect of antioxidant vitamins A, C, E and their analogues against DNA damage induced by a hepatocarcinogen p-dimethylaminoazobenzene (DAB) was assessed by comet assay. For genotoxicity (DNA damage) study, male albino rats were divided into 11 groups, consisting of four rats each. Group I served as control. Group II to VII received 1, 10, 100, 200, 300 and 400 mg per kg body wt of DAB respectively; group VIII to XI received 500 mg/kg body wt of DAB. They were sacrificed by cervical decapitation 3, 6, 12 and 24 h after treatment; livers were excised immediately and subjected to comet assay to measure DNA damage. To study the effect of vitamins, experiments were conducted on a group of 275 rats divided into 3 sets of 25 rats each. First set served as control; second set received 0.06% DAB and third set received 0.06% DAB, along with analogues of vitamins A, C and E. Rats fed with 0.06% DAB were provided water ad libitum for a period of 4 months, followed by a normal (basal) diet for further 2 months. Vitamins A (10,000-50,000 IU), C (75-1000 mg) and E (50-500 mg) and their analogues were given (per kg body wt) to the third set of rats by gavage route once in a week for a period of 6 months. The DAB induced DNA damage only at the highest tested dose of 500 mg/kg body wt. Administration of high doses of vitamin A acid, L-ascorbic acid and vit. E succinate individually prevented the DNA damage. However, administration of a mixture of these vitamins at low doses prevented the DAB-induced DNA damage, which may be due to their synergistic effect. The results indicate that there is a significant advantage in mixed vitamins therapy at low dose over the treatment with individual vitamins.