Human xanthine dehydrogenase cDNA sequence and protein in an atypical case of type I xanthinuria in comparison with normal subjects

To investigate the properties of xanthine dehydrogenase/xanthine oxidase (XDH/XO) deficiency in a patient with atypical type I xanthinuria, as indicated by oxypurine data, a cDNA sequence encoding XDH, XDH/XO immunoblot analysis and a competitive PCR assay were performed, and the results were compared with those of normal subjects. The xanthine dehydrogenase cDNA sequence of the patient was consistent with the controls, while immunologically reactive 150 kD XDH/XO protein was not present in the xanthinuric duodenal mucosa, unlike the control duodenal mucosa. In addition, a decrease in XDH/XO messenger RNA was found by competitive PCR. These results suggest that atypical type I xanthinuria is due to a decrease in messenger RNA of XDH/XO. Furthermore, it was considered that this decrease could explain the normal plasma level and near normal urinary excretion of hypoxanthine seen in this case of xanthinuria, though XDH/XO activity and protein were not detected spectrophotometrically and immunologically, respectively.     

Chronic cold exposure affects the antioxidant defense system in various rat tissues

BACKGROUND: Chronic exposure to stress alters the normal body homeostasis and, hence, leads to the development of various human pathologies, which might involve alterations in the antioxidant defense system. We studied the effect of chronic cold exposure on oxidative stress and antioxidant defense system in various rat tissues. METHODS: Male albino rats (Wistar strain), 2-3 months old, were exposed to 3 weeks of cold treatment. Antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) were measured in addition to the antioxidants, ascorbic acid (AsA) and glutathione (GSH), and the prooxidants, lipid peroxides (LPO) and xanthine oxidase (XOD), in brain, heart, kidney, liver and small intestine using standard protocols. RESULTS: Chronic cold exposure resulted in a significant increase in LPO in all the tissues studied while XOD was increased in the brain and intestine. Total SOD activity was significantly decreased in all the tissues, whereas CAT activity was significantly increased in the kidney and decreased in heart, liver and intestine in the animals exposed to cold. GPx activity was increased only in the brain and intestine of stressed rats. Chronic cold exposure resulted in significant decrease in GR activity in heart, liver and intestine. GST activity was increased (except heart) and GSH was significantly decreased in all the tissues in treated rats. AsA was increased in kidney and intestine but decreased in heart of stressed animals. CONCLUSIONS: The observed changes in the antioxidant defense system are tissue specific, but it is evident that chronic exposure to cold leads to oxidative stress by displacing the prooxidant-antioxidant balance of this defense system by increasing the prooxidants while depleting the antioxidant capacities.     

Red Cabbage (Brassica oleracea) Ameliorates Diabetic Nephropathy in Rats

The protective action against oxidative stress of red cabbage (Brassica oleracea) extract was investigated. Diabetes was induced in male Wistar rats using streptozotocin (60 mg/kg body weight). Throughout the experimental period (60 days), diabetic rats exhibited many symptoms including loss of body weight, hyperglycemia, polyuria, polydipsia, renal enlargement and renal dysfunction. Significant increase in malondialdehyde, a lipid peroxidation marker, was observed in diabetic kidney. This was accompanied by a significant increase in reduced glutathione and superoxide dismutase activity and a decrease in catalase activity and in the total antioxidant capacity of the kidneys. Daily oral ingestion (1 g/kg body weight) of B. oleracea extract for 60 days reversed the adverse effect of diabetes in rats. B. oleracea extract lowered blood glucose levels and restored renal function and body weight loss. In addition, B. oleracea extract attenuated the adverse effect of diabetes on malondialdehyde, glutathione and superoxide dismutase activity as well as catalase activity and total antioxidant capacity of diabetic kidneys. In conclusion, the antioxidant and antihyperglycemic properties of B. oleracea extract may offer a potential therapeutic source for the treatment of diabetes.     

Effects of caffeic acid phenethyl ester on lipid peroxidation and antioxidant enzymes in diabetic rat heart

OBJECTIVES: The risk for cardiovascular disease is significantly high in diabetes mellitus. Experimental evidence suggests that oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. Caffeic acid phenethyl ester (CAPE), an active component of propolis, has several biological and pharmacological properties, including antioxidant, anti-inflammatory, anti-carcinogenic, antiviral, and immunomodulatory activities. In light of the antioxidant ability of CAPE, the effects of CAPE on the antioxidative status of cardiac tissue were investigated in streptozotocin (STZ)-induced diabetic rats. DESIGN AND METHODS: Twenty-six rats were randomly divided into three groups: group I, control, nondiabetic rats (n = 9); group II, STZ-induced, untreated diabetic rats (n = 7); and group III, STZ-induced, CAPE-treated diabetic rats (n = 10). In groups II and III, diabetes developed 3 days after intraperitoneal (ip) administration of a single 35 mg kg(-1) dose of STZ. Thereafter, while the rats in group II received no treatment, the rats in group III began to receive a 10 mumol kg(-1) ip dose of CAPE per day. After 8 weeks, the levels of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the cardiac tissues of all groups were analyzed. RESULTS: In untreated diabetic rats, MDA markedly increased in the cardiac tissue compared with the control rats (P < 0.05). However, MDA levels were reduced to the control level by CAPE. The activities of SOD and CAT in the untreated diabetic group and the CAPE-treated diabetic group were higher than those of the control group (P < 0.05). Rats in the CAPE-treated diabetic group had reduced activities of SOD and CAT in comparison with the rats in the untreated diabetic group (P < 0.05). There were no significant differences in the activity of GSH-Px between the rats in the untreated diabetic group and the control group. However, the activity of GSH-Px was increased in CAPE-treated diabetic rats compared with the control and untreated diabetic rats (P < 0.05). CONCLUSION: These results reveal that diabetes mellitus increases oxidative stress in cardiac tissue and CAPE has an ameliorating effect on the oxidative stress via its antioxidant property.     

Normothermic liver ischemia in rats: xanthine oxidase is not the main source of oxygen free radicals

We studied the effect of allopurinol (ALL) on the activity of xanthine dehydrogenase (XDH), xanthine oxidase (XOX), superoxide dismutase (SOD), and catalase (CAT) in rat liver during ischemia followed by 60 min of reperfusion. We induced 60-min ischemia in the median and left lobes by clamping the hepatic artery and portal branches. The percentage XOX relative to total oxidase activity increased significantly in the control group, from 10% during the stabilization period to 18% after 60 min of reperfusion. The XDH activity decreased during reperfusion. Activity of both XDH and XOX was almost completely blocked by ALL. The activity of SOD and CAT did not differ significantly between the ALL group and controls after 60 min of reperfusion. ALL treatment did not affect liver injury parameters, as concentrations of lactate dehydrogenase (LDH) and alanine transferase (ALT) increased in plasma after ischemia, both in controls and in the ALL-treated group. We concluded that ischemia promotes conversion of XDH to XOX during reperfusion. XOX may not be the main source of free radical production, since intracellular scavengers (SOD and CAT) did not differ significantly between controls and the ALL-treated group, despite the fact that ALL blocked XOX activity completely.     

黄连素对实验性2型糖尿病大鼠黄嘌呤氧化酶的影响

目的观察黄连素对实验性2型糖尿病大鼠血清、肾脏中黄嘌呤氧化酶(XOD)活性的影响及肾脏组织学改变。方法采用小剂量链脲佐菌素加高糖高脂饲料喂养的方法建立Wistar大鼠2型糖尿病模型,成模后给予黄连素0.1g.kg-1.d-1灌胃治疗8周,检测大鼠空腹血糖(FPG)的变化,血清和肾脏中黄嘌呤氧化酶(XOD)活性的变化,观察肾脏组织学改变。结果与糖尿病组相比,黄连素治疗组血清和肾组织黄嘌呤氧化酶(XOD)活性明显降低(P<0.01)。黄连素组大鼠肾脏组织仅见内皮细胞数目稍有增加,较糖尿病组大鼠有所改善。结论黄连素可降低大鼠体内黄嘌呤氧化酶活性、延缓DM肾脏的发生和发展。     

Insulin and losartan reduce proteinuria and renal hypertrophy in the pregnant diabetic rat

This study was designed to investigate the effect of hyperglycemia and angiotensin II (AngII) on renal hypertrophy and proteinuria in the pregnant diabetic rat. Secondary objectives were to evaluate changes in components of the renin-angiotensin axis and the effects of administration of losartan on pregnancy outcome. Fifty-three pregnant rats were allocated to 6 groups (1) nondiabetic controls (n = 12), (2) nondiabetic controls administered losartan (70-80 mg/kg/day; n = 10), (3) rats in which intravenous streptozotocin (STZ) was used to induce diabetes (55 mg/kg on day 10 of pregnancy; n = 10), (4) diabetic rats treated with losartan (n = 7), (5) diabetic rats treated with insulin (4 U/day; n = 7), and (6) diabetic rats treated with insulin and losartan (n = 7). Urinary protein excretion measured 4 days after STZ was 4 times greater in the rats with STZ-induced diabetes and significantly less in diabetic rats given losartan, insulin, or both. Postpartum kidney weight was greater in the rats with STZ-induced diabetes (2.04 +/- 0.21 g) than in the controls (1.37 +/- 0.14 g; P <.05) and reduced in the diabetic rats given losartan, insulin, or both (1.57 +/- 0.22, 1.73 +/- 0.13, and 1.51 +/- 0.14 g, respectively; P <.05). Plasma levels of angiotensin II in rats given losartan were more than 3.5 times greater than those in controls (749 +/- 436, 596 +/- 323, 567 +/- 349, and 159 +/- 28 pg/mL; P <.001). Postpartum activity of angiotensin-converting enzyme was increased in the untreated diabetic rats compared with that in control rats (162 +/- 12 vs 117 +/- 16 nmol/mL/min; P <.05). This increase was abolished by treatment with losartan or insulin. The number of newborns and mean weight of each newborn was similar in all groups. In summary, administration of losartan or insulin prevented, in part, kidney hypertrophy and protein excretion in the diabetic pregnant rat. Losartan did not affect the number or weight of newborns. Because angiotensin II receptor-blockers are contraindicated in pregnancy, good control of diabetes through the use of insulin should be advantageous.     

Monotherapy with metformin: does it improve hypoxia in type 2 diabetic patients?

Metformin reduces blood glucose levels predominantly by inhibiting hepatic gluconeogenesis, although it also may enhance insulin receptor number or activity. The full effects of metformin are still poorly understood. In this study the effects of metformin on plasma xanthine oxidase (XO) activity, thiobarbituric acid-reactive substance (TBARS), lactate and fructosamine concentration as well as erythrocyte antioxidant enzyme activities were investigated in 46 patients with type 2 diabetes mellitus. All parameters were measured simultaneously just before metformin therapy (T0), 1 month (T1) and 2 months (T2) later. Results were compared with placebo and control group. We noted significant decrease in XO activity and in TBARS concentration (p<0.001) during monotherapy with metformin vs. placebo and T0 group. A significant correlation was observed between the activity of XO and the concentration of fructosamine (p<0.001). Erythrocyte glutathione peroxidase showed significantly lower activity in T2 group in comparison with T0 group (p<0.01). It is known that diabetic patients produce more TBARS as a result of enhanced free radical generation the source of which may also be the large amounts of XO produced following the conversion of xanthine dehydrogenase in hypoxic diabetic tissues. Thus, our results indirectly suggest that metformin can reduce toxic tissue damage through the inhibition on XO activity.     

嘌呤核苷酸补偿对海洛因依赖大鼠嘌呤核苷酸代谢相关酶基因表达的影响

目的探讨外源性补偿嘌呤核苷酸对海洛因依赖大鼠嘌呤核苷酸代谢酶的影响。方法将50只雄性Wis-tar大鼠随机分为对照组、海洛因组、海洛因+AMP+GMP组、海洛因+AMP组、海洛因+GMP组。采用real-timePCR的方法检测大鼠脑皮质中腺苷脱氨酶(ADA)、黄嘌呤氧化酶(XO)、次黄嘌呤-鸟嘌呤磷酸核糖转移酶(HGPRT)、腺嘌呤磷酸核糖转移酶(APRT)和腺苷激酶(AK)mRNA的表达水平。结果海洛因组ADA、XO的mRNA比对照组明显升高(P0.05),而海洛因+AMP+GMP组、海洛因+AMP组、海洛因+GMP组与海洛因组相比明显降低(P0.05)。海洛因组HGPRT、APRT和AK的mRNA比对照组明显降低(P0.05),而海洛因+AMP+GMP组、海洛因+AMP组、海洛因+GMP组与海洛因组相比有不同程度升高,以HGPRT的升高程度尤为显著(P0.05)。海洛因+AMP+GMP组、海洛因+AMP组、海洛因+GMP组的各项指标差异无显著性。结论海洛因在大鼠基因水平上促进嘌呤核苷酸的分解代谢,降低合成代谢,而补偿嘌呤核苷酸可以抑制或拮抗海洛因的上述作用。     

Antioxidant role of mulberry (Morus indica L. cv. Anantha) leaves in streptozotocin-diabetic rats

BACKGROUND: The antihyperglycemic and antioxidant role of mulberry (Morus indica L.) leaves were investigated. METHODS: Streptozotocin (STZ)-induced diabetic male Wistar rats were used as experimental models; one group was given 25% dry mulberry leaf powder mixed with the standard diet and another group was given standard diet for a period of 8 weeks. The antihyperglycemic and antioxidant role of mulberry was assessed by determining its effect on blood glucose, lipid peroxidation, reduced glutathione (GSH) concentrations and on the activity of glucose-6-phosphate dehydrogenase (G6PDH) and various antioxidant enzymes in erythrocytes and compared with that of controls. RESULTS: Mulberry-treated diabetic rats showed a significant decrease in fasting blood glucose concentrations indicating a good glycemic control. Increased lipid peroxidation and the activity of catalase (CAT) in erythrocytes observed in diabetic controls were significantly decreased by mulberry leaves (48% and 33%, respectively). Decreased GSH concentrations and the activity of glucose-6-phosphate dehydrogenase and antioxidant enzymes viz., glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and superoxide dismutase (SOD) observed in uncontrolled diabetes were improved (52%, 69%, 151%, 95%, 24% and 106%) by mulberry treatment very efficiently. CONCLUSION: Mulberry leaves possess antihyperglycemic and antioxidant properties.     

Effect of macrocyclic binuclear oxovanadium complex on tissue defense system in streptozotocin-induced diabetic rats

BACKGROUND: Oxidative stress plays an important role in chronic complications of diabetes mellitus and hence the regulation of free radicals is essential in the treatment of diabetes. The protective effect of a new macrocyclic binuclear oxovanadium complex on antioxidant defense systems of liver and kidney was examined in streptozotocin-induced experimental diabetes in rats. METHODS: The levels of lipid peroxides, glutathione and the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase were assayed according to standard procedures in the liver and kidney of control and experimental groups of rats. RESULTS: A significant decrease (p < 0.05) was observed in both the glutathione content and in the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase and a concomitant increase in the level of lipid peroxides in diabetic rats. The observed alterations in the antioxidant status of tissues reverted back to near normal levels after the oral administration of macrocyclic vanadium complex at a dose of 5 mg/kg body weight/rat/day for a period of 30 days. CONCLUSION: The normoglycemic efficacy of the vanadium complex alleviates oxidative stress in streptozotocin-induced diabetes in rats.     

葡萄糖-6-磷酸脱氢酶缺乏的红细胞抗氧化能力的研究

本文探讨了正常和葡萄糖-6-磷酸脱氢酶(G-6-PD)缺乏的红细胞抗氧化能力的不同。结果显示,G-6-PD缺乏的红细胞还原型辅酶Ⅱ(NADPH)含量显著低于正常红细胞;正常红细胞受过氧化刺激后,其过氧化氢酶(Cat)、谷胱甘肽过氧化物酶(GSHpx)活性及NADPH含量均呈现先升后降的变化;G-6-PD缺乏的红细胞的Cat,GSHpx活性及NADPH含量则持续下降。揭示了G-6-PD缺乏的红细胞抗氧化能力不足。本文还对NADPH在红细胞抗氧化中所起的作用进行了探讨。     

应用心肌自发荧光评估存活心肌线粒体氧化代谢状态

目的：应用心肌自发荧光（AF）研究心肌线粒体氧化代谢状态,监测线粒体功能改变的早期信号。方法：烟酰胺腺嘌呤（磷酸）二核苷酸ENAD（P）HI作为荧光探针,用光谱分辨的时间相关单光子计数（TCSPC）记录375nm紫外激光激发的心肌AF光谱和荧光寿命,测试影响线粒体呼吸时AF动态衰减。结果：在420～560nm光谱区域,至少需用3个荧光寿命池0．4～0．7ns,1．2～1．9ns和8．0～13．0ns描述细胞AF。线粒体呼吸阻断剂鱼藤酮可显著增加AF强度,缩短平均荧光寿命。氧化磷酸化解偶联剂二硝基酚可显著降低AF强度,在520nm处增宽荧光光谱,延长平均荧光寿命。这些结果和NADH荧光动力学离体实验（invitro）有可比性。结论：光谱分辨的荧光寿命技术测定心肌NAD（P）H荧光有很好的重复性,在细胞水平上增加了心肌氧化代谢或线粒体功能障碍的知识,为临床诊断和治疗线粒体功能障碍开拓了新视野。     

All-trans Arachidonic acid generates reactive oxygen species via xanthine dehydrogenase/xanthine oxidase interconversion in the rat liver cytosol in vitro

We previously reported that the all-cis isomer of arachidonic acid, the most naturally occurring isoform of this fatty acid, reduced cuprous copper ion-induced conversion of xanthine dehydrogenase into its reactive oxygen species generating form, xanthine oxidase. In the present study, the effects of all-trans isomer of arachidonic acid, in comparison with cis isomer of arachidonic acid, on the xanthine dehydrogenase/xanthine oxidase interconversion were explored. cis isomer of arachidonic acid alone did not have any significant effect on the activities of xanthine dehydrogenase and xanthine oxidase, but it inhibited the cuprous copper ion-induced conversion of xanthine dehydrogenase to xanthine oxidase in rat liver cytosol in vitro. In contrast, trans isomer of arachidonic acid elicited an increase in xanthine oxidase activity concomitant with a decrease in xanthine dehydrogenase activity, and further potentiated the cuprous copper ion-induced xanthine dehydrogenase/xanthine oxidase interconversion. In primary rat hepatocyte cultures, trans isomer of arachidonic acid increased 2',7'-dichlorofluorescein-fluorescence intensity in the cytosolic fraction from 2',7'-dichlorodihydrofluorescein, an indicator of reactive oxygen species generation. The pretreatment of allopurinol, an xanthine oxidase inhibitor, diminished the trans isomer of arachidonic acid-induced increase in the 2',7'-dichlorofluorescein-fluorescence intensity, indicating the role of xanthine dehydrogenase/xanthine oxidase in mediating trans isomer of arachidonic acid-induced reactive oxygen species generation. These observations suggest that, in contrast to all-cis arachidonic acid, all-trans arachidonic acid has the potential to enhance reactive oxygen species generation via xanthine dehydrogenase/xanthine oxidase interconversion in the liver cytosol in vitro.     

Anti-oxidant and Anti-hypercholesterolemic Activities of Wasabia japonica

The effects of Wasabia japonica (WJ) were investigated in vitro and in vivo for their anti-oxidant and anti-hypercholesterolemic activities. It was found that the aqueous extracts of WJ leaves (WJL) had strong scavenging activities towards 1,1-Diphenyl-2-picryhydrazyl (DPPH) and nitric oxide (NO) free radicals in cell free systems. WJL also inhibited NO production and the expressions of inducible NO synthase (iNOS) mRNA and enzyme protein, determined by Griess reactions, RT-PCR or Western blotting respectively in Lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages cells. The anti-hypercholesterolemic effects of WJ diet were investigated in hypercholesterolemia rats. Sprague-Dawley rats were divided into four groups and were fed with either normal diet (Group 1), or diet containing 1%(w/w) cholesterol (Groups 2, 3 and 4). After 4 weeks, Group 2 was changed to normal diet, Groups 3 and 4 were changed to the diet containing 5% WJ leaf and or 5% WJ root, respectively. 3 weeks after WJ diets, Serum HDL-cholesterol levels were significantly increased in WJ diet groups compared with the normal diet hypercholesterolemia rats. In contrast, the serum LDL-cholesterol levels and liver xanthine oxidase (XO) activity in WJ diet groups were significantly decreased. The results indicate that the WJ extracts have significant anti-oxidant activities, and the WJ diet exhibited anti-hypercholesterolemic action in high cholesterol diet rats, which was companied with modulations of cholesterol metabolism and decrease in liver XO activity.     

Decrease of ischaemia-reperfusion related lung oedema by continuous ventilation and allopurinol in rat perfusion lung model

Okuda M, Furuhashi K, Nakai Y, Muneyuki M. Decrease of ischaemia-reperfusion related lung oedema by continuous ventilation and allopurinol in rat perfusion lung model. Scand J Clin Lab Invest 1993; 53: 625-631.

Using isolated perfusion rat lung model, we studied the effect of continuous ventilation without perfusion and allopurinol on the development of ischaemia-reperfusion lung injury. Ischaemia was induced by stopping the perfusion. Nor-mothermic ischaemia for 90 min without ventilation caused significant lung oedema. Continuous ventilation during ischaemia with 21 % O2 decreased lung oedema significantly after 60 min of reperfusion. The same protection could be achieved by 100% N₂ ventilation during 90 min of ischaemia, suggesting that xanthine oxidase (XO) is unlikely to cause the ischaemia-reperfusion lung injury. On the other hand allopurinol, XO inhibitor, equally inhibited lung oedema after 90 min of ischaemia and 60 min of reperfusion. These results indicate that mechanical movement of alveoli provides successful preservation of ischaemic lung, and allopurinol has some protective effect other than XO inhibition.     

结缔组织生长因子在糖尿病大鼠肾脏中的表达

目的 通过观察结缔组织生长因子（CTGF）在糖尿病大鼠肾脏中表达的动态改变,探讨CTGF在糖尿病肾病发生发展中的作用。方法 尾静脉内注射链脲佐菌素（STZ）诱导糖尿病大鼠模型。采用RT-PCR和Western blot检测1个月、3个月和6个月时糖尿病大鼠肾脏组织中CTGF的mRNA和蛋白的表达。光镜下观察糖尿病大鼠不同时期肾脏组织形态学的改变。结果 糖尿病大鼠1个月、3个月和6个月与同期对照大鼠相比,肾脏CTGF的mRNA表达上调,分别为对照组的1.56倍、2.05倍和3.74倍（P〈0.01）;同时蛋白表达亦上调,分别为对照组的2.48倍、2.93倍和5.82倍（P〈0.01）;此外,糖尿病6个月大鼠的CTGF mRNA和蛋白的表达明显高于糖尿病1个月和3个月大鼠的表达水平（P〈0.01）。组织形态学观察表明,糖尿病大鼠3个月时肾脏出现基膜增厚、肾小球扩张等糖尿病肾病早期的病理改变,随着病程的延长,病理改变越严重;6个月时出现肾小球硬化、肾间质纤维化等晚期的改变。结论 糖尿病大鼠早期肾脏已存在CTGF基因表达上调,在糖尿病肾病的发展过程中,CTGF基因表达上调仍持续存在。因此,CTGF基因表达上调在糖尿病肾病的发生发展中起着重要作用。     

Decreasing effects of iron toxicosis on selenium and glutathione peroxidase activity

Heart failure due to chronic iron overload is a leading cause of cardiovascular mortality in the second and third decades of life worldwide, but its mechanism is not known. Deficiencies of selenium have been shown to result in damage to the myocardium and to the development of various cardiomyopathies. In the current investigation, the dose-dependent effects of chronic iron toxicosis on heart tissue concentrations of selenium and the protective antioxidant enzyme glutathione peroxidase (GPx) were investigated in a murine model of iron-overload cardiomyopathy (n = 20). Significant dose-dependent decreases in heart tissue selenium concentrations (r = -0.95, p < 0.001) and selenium-dependent GPx activity (r = -0.93, p < 0.001) were observed in chronically iron-loaded mice in comparison with placebo controls. These results suggest that dietary supplementation with selenium may be beneficial in the clinical management of disorders of iron metabolism.     

Antioxidant Activity and Lipid-Lowering Effect of Essential Oils Extracted from Ocimum sanctum L. Leaves in Rats Fed with a High Cholesterol Diet

It has been reported that Ocimum sanctum L. (OS) leaves decrease serum lipid profile in normal and diabetic animals. No experimental evidences support the anti-hyperlipidemic and antioxidative actions against hypercholesterolemia. Moreover the identity of the specific chemical ingredients in OS leaves responsible for these pharmacological effects are unknown. Since OS leaves are rich in essential oil (EO). Therefore the present study was conducted to investigate the anti-hyperlipidemic and antioxidative activities of EO extracted from OS leaves in rats fed with high cholesterol (HC) diet. EO was extracted by the hydrodistillation method and the chemical constituents were then identified by Gas Chromatography-Mass Spectrometry. The experiment was performed in Male Wistar rats fed with 2.5 g%(w/w) of cholesterol diet for seven weeks. During the last 3 weeks, rats were daily fed with EO. The results showed that phenyl propanoid compounds including eugenol and methyl eugenol were the major constituents of EO. EO suppressed the high serum lipid profile and atherogenic index as well as serum lactate dehydrogenase and creatine kinase MB subunit without significant effect on high serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in rats fed with HC diet. In addition, EO was found to decrease the high levels of thiobarbituric acid reactive substances (TBARS), glutathione peroxidase (GPx) and superoxide dismutase (SOD) without impacting catalase (CAT) in the cardiac tissue while in the liver, it decreased high level of TBARS without significantly effecting GPx, SOD and CAT. Histopathological results confirmed that EO preserved the myocardial tissue. It can be concluded that EO extracted from OS leaves has lipid-lowering and antioxidative effects that protect the heart against hypercholesterolemia. Eugenol that is contained in EO likely contribute to these pharmacological effects.