Protective effect of testosterone on early apoptotic damage induced by streptozotocin in rat pancreas

Beta-cell apoptosis is responsible for the development of insulin-dependent diabetes mellitus in the streptozotocin (STZ) rat model. It has been demonstrated that steroid hormones possess antioxidant and protective antiapoptotic effects in many tissues. The aim of the present study was to investigate the early apoptotic damage induced by STZ in rat pancreas, and the effect of testosterone in preventing apoptosis of pancreatic beta cells. Intact and castrated adult male Wistar rats were subjected to a unique injection of STZ 60 mg/kg (body weight) in citrate buffer, and the kinetics of apoptosis in beta cells was assessed. Insulin and glucose were measured by RIA and a glucometer respectively, and in pancreatic tissue by immunohistochemistry. At 6 h after STZ injection, a marked increase in apoptotic beta cells was detected; however, glucose and insulin serum levels were not significantly different from the controls. The castrated animals presented higher percentages of apoptotic beta cells (65.75 +/- 5.42%) than intact males (20.6 +/- 4.38%) and castrated, testosterone-substituted males (30.66 +/- 1.38%). The decrease in apoptotic beta cells induced by testosterone was reversed by the antiandrogen flutamide (67.69 +/- 3.45%). The overall results indicate that early apoptotic damage produced by STZ in castrated animals was reversed by testosterone, suggesting that this hormone exerts a natural protective effect in rat pancreas. This effect could help to explain some sexual differences in diabetes mellitus incidence in man, reinforcing the idea that new approaches in steroid hormone therapies should be considered for treatment of this disease.     

Nicorandil improves diabetes and rat islet beta-cell damage induced by streptozotocin in vivo and in vitro

OBJECTIVE: N-(2-hydroxyethyl)-nicotinamide nitrate (nicorandil) is a unique anti-anginal agent, reported to act as both an ATP-sensitive K(+) channel opener (PCO) and a nitric oxide donor. It also has an anti-oxidant action. We examined the effects of nicorandil on streptozotocin (STZ)-induced islet beta-cell damage both in vivo and in vitro. DESIGN AND METHODS: STZ-induced diabetic Brown Norway rats (STZ-DM) were fed with nicorandil-containing chow from day 2 (STZ-DM-N48), 3 (STZ-DM-N72), and 4 (STZ-DM-N96) to day 30. Body weight, blood glucose, and plasma insulin were measured every week. For the in vitro assay, neonatal rat islet-rich cultures were performed and cells were treated with nicorandil from 1 h before to 2 h after exposure to STZ for 30 min. Insulin secretion from islet cells was assayed after an additional 24 h of culture. We also observed the effect of nicorandil on the generation of reactive oxygen species (ROS) from rat inslinoma cells (RINm5F). RESULTS: Body weight loss and blood glucose levels of STZ-DM-N48 rats were significantly lower than those of STZ-DM rats. Immunohistochemical staining of insulin showed preservation of insulin-secreting islet beta-cells in STZ-DM-N48 rats. Nicorandil also dose-dependently recovered the insulin release from neonatal rat islet cells treated with STZ in in vitro experiments. Nicorandil did not act as a PCO on neonatal rat islet beta-cells or RINm5F cells, and did not show an inhibitory effect on poly(ADP-ribose) polymerase-1. However, the drug inhibited the production of ROS stimulated by high glucose (22.0 mmol/l) in RINm5F cells. CONCLUSIONS: These results suggested that nicorandil improves diabetes and rat islet beta-cell damage induced by STZ in vivo and in vitro. It protects islet beta-cells, at least partly, via a radical scavenging effect.     

Effect of oxidative stress-associated damage to the lung tissue caused by different body mass index in the rat models

正Objective To investigate the influence of different diets on serum protein expression levels of 4-hydroxynonenal(4-HNE),thioredoxin(Trx),thioredoxin reductase(TrxR)and the sctivities of Trx and TrxR,and to explore the effect of damage to the lung tissue and the underlying mechanisms of different body mass index caused by different diets in the rat models.Methods Healthy     

Melatonin protects against oxidative mitochondrial damage induced in rat placenta by ischemia and reperfusion

We assessed the effects of melatonin, a powerful scavenger of oxygen free radicals, on ischemia/reperfusion-induced oxidative damage to mitochondria in the rat placenta. In Wistar rats at day 19 of pregnancy, feto-placental ischemia was induced by occluding both utero-ovarian arteries for 20 min. Reperfusion was achieved by releasing the occlusion and restoring circulation for 30 min. Melatonin solution or the vehicle alone was injected intraperitoneally at dose of 10 mg/kg 1 hr before occlusion. Sham-ischemic animals were treated with vehicle. Each group consisted of 10 pregnant rats. We measured placental mitochondrial respiratory control index (RCI; a marker of mitochondrial respiratory activity), the ratio of the added adenosine 5-diphosphate (ADP) concentration to consumption of oxygen during state 3 respiration (ADP/O), and the concentration of thiobarbituric acid reactive substances (TBARS) in each group. RCI and ADP/O were significantly decreased by ischemia/reperfusion, while TBARS were increased. Melatonin prevented these changes. These results indicate that exogenous melatonin protects against ischemia/reperfusion-induced oxidative damage to mitochondria in rat placenta. Melatonin could be useful in treating preeclampsia and possibly other clinical states involving excess free radical production, such as fetal growth restriction and fetal hypoxia.     

香烟烟雾提取物对大鼠股四头肌细胞氧化损伤的研究

目的 研究经香烟烟雾提取物（CSE）刺激后大鼠股四头肌细胞8-羟基脱氧鸟苷（8-OHdG）含量的变化以及细胞内活性氧（ROS）水平和8-羟基鸟嘌呤DNA糖苷酶1（OGG1）表达对8-OHdG含量变化的影响.方法 用不同浓度CSE分别刺激大鼠股四头肌细胞24 h、48 h和72 h后,采用高效液相色谱-电化学法（HPLC-ECD）检测大鼠股四头肌细胞8-OHdG的含量,流式细胞术检测大鼠股四头肌细胞ROS水平,实时定量PCR（Realtime PCR）检测OGG1 mRNA水平,用Western blot检测OGG1蛋白水平.结果 经相同CSE浓度分别刺激大鼠股四头肌细胞24 h、48 h和72 h后,大鼠股四头肌细胞中8-OHdG含量、ROS水平及OGG1 mRNA和蛋白水平差异均无统计学意义.但经不同浓度CSE刺激相同时间后,10.00％ CSE和20.00％CSE刺激组大鼠股四头肌细胞8-OHdG含量明显高于对照组和5.00％ CSE刺激组（P＜0.05）;大鼠股四头肌细胞内ROS水平、OGG1 mRNA和蛋白水平较对照组均明显升高（P＜0.05）;大鼠股四头肌细胞8-OHdG含量与其ROS水平呈明显正相关（r=0.746,P＝0.000）;经CSE刺激后,大鼠股四头肌细胞OGG1 mRNA和蛋白水平均高于对照组（P＜0.05）,但大鼠股四头肌细胞8-OHdG含量与其OGG1 mRNA和蛋白水平无明显相关（r=0.392,P＝0.536;r=0.297,P=0.426）.结论 CSE刺激可引起大鼠股四头肌细胞8-OHdG升高,8-OHdG含量与ROS水平有关,但与其修复酶OGG1表达水平无明显相关.     

The rat models of non-insulin dependent diabetes induced by neonatal streptozotocin

This review is intended to describe the characteristics of the rat models of non-insulin-dependent diabetes induced by neonatal streptozotocin administration (n-STZ models), to sum-up the information so far collected and to highlight the potential of these models for diabetes research. The n-STZ models can now be recognized as adequate tools for the elucidation of the mechanisms leading to: 1) regeneration of the beta cells, 2) the functional "exhaustion" of the beta cells, 3) the emergence of defects in insulin action. They appear well-suited to study the effects of the modulating factors involved in the appearance and/or deterioration of non-insulin-dependent diabetes (obesity, gestation, content of the diet). They are potentially appropriate for investigations in diabetes pharmacotherapy.     

不同浓度地黄对大鼠肾组织抗氧化作用的研究

目的观察不同浓度地黄对肾脏组织抗氧化作用的影响,探讨地黄在治疗肾病时的适宜剂量。方法将患者分为6组,其中空白组不给任何药物,模型对照组单纯造模而不给药物,阳性对照组给予维生素E,高、中、低浓度给药组（分别给予地黄6.5 mg/ml,3.25 mg/ml和1.625 mg/ml）。分别测定各组处理后H2O2诱导的大鼠肾匀浆脂质过氧化、大鼠肾匀浆产生自发性脂质过氧化产物丙二醛（MDA）的含量以计算MDA抑制率,及对诱导红细胞溶血的溶血率。结果阳性对照组、高、中、低浓度给药组MDA抑制率均较模型对照组高（P均〈0.05）,而高、低浓度给药组MDA抑制率较中浓度给药组低（P均〈0.05）,且中浓度给药组MDA抑制率与阳性对照组无统计学差异（P〉0.05）;阳性对照组、高、中、低浓度给药组溶血率均较模型组低（P〈0.05）,而高、低浓度给药组溶血率较中浓度给药组高（P均〈0.05）,且中浓度给药组溶血率与阳性对照组无统计学差异（P〉0.05）。结论不同浓度的地黄均有明显的抗氧化作用,且抗氧化作用与剂量相关。在治疗肾脏疾病的复方配伍中,地黄宜用中等量。     

茶多酚对饮茶型氟中毒大鼠关节软骨氧化损伤的保护作用

目的 探讨茶多酚对饮茶型氟中毒大鼠关节软骨的氧化应激损伤的保护作用.方法 120只雄性Wistar大鼠按体质量随机分为6组:对照组、加氟组、氟+茶多酚组、氟+铝组、氟+铝+茶多酚组和砖茶组.加氟组每日饮用含氟(F-)100.00 mg/L的氟化钠(NaF)水溶液;氟+茶多酚组每日饮用含F-100 mg/L、茶多酚10.0 g/L的水溶液;氟+铝组每日饮用含F-100.00 mg/L、铝(Al3+)200.00 mg/L的水溶液;氟+铝+茶多酚组同时饮用含有上述3种物质的水溶液:砖茶组饮用砖茶沏制而成的砖茶水(F- 100.00 mg/L、Al3+215.00mg/L、9.2 g/L);对照组饮用自来水(F- 0.33 mg/L).连续饲养3个月,处死动物,检测血清中超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)、戊二醛(MDA)、一氧化氮(NO)和细胞因子白介素1β(IL-1β)、白介素6(IL-6)的水平;RT-PCR和免疫组化法检测关节软骨中诱生型一氧化氮合酶(iNOS)mRNA及蛋白表达.结果 氟 +铝+茶多酚组SOD水平[(664.009±29.589)kU/L]与加氟组、氟+销组[(625.328±27.199)、(652.282±13.926)kU/L]比较有升高趋势,但是差异无统计学意义(P均>0.05);氟+茶多酚组、氟+铝+茶多酚组、砖茶组T-AOC水平[(10.874±0.721)、(11.871±0.941)、(10.380±2.747)kU/L]与加氟组、氟+铝组[(8.849±1.887)(8.210±1.740)kU/L]比较,差异有统计学意义(P均<0.05);氟+铝+茶多酚组血清中MDA水平[(3.235±0.446)μmol/L]与加氟组、氟+铝组[(3.889±0.387)、(4.580±0.474)μmol/L]比较,差异有统计学意义(P均<0.05);氟+茶多酚组、氟+铝+茶多酚组、砖茶组血清中NO水平[(23.278±2.386),(20.643±2.623)、(24.367±6.072)μmol/L]与加氟组、氟+铝组[(32μ962±8.268)、(34.909±6.288)μmol/L]比较,差异有统计学意义(P均<0.05):加氟组、氟+销组、氟+茶多酚组、氟+铝+茶多酚组、砖茶组血清IL-1β水平分别为(4.728±0.297)、(4.412±0.229)、(4.432±0.285)、(4.516±0.351)、(4.614±0.2270)ng/L,组间比较,差异无统计学意义(F=2.314,P>0.05);氟+铝+茶多酚组、砖茶组IL-6水平[(7.231±0.596)、(7.325±0.290)ng/L]与氟+铝组[(8.256±0.635)ng/L]比较,差异有统计学意义(P均<0.05).氟+茶多酚组、氟+铝+茶多酚组、砖茶组iNOS mRNA相对表达量(0.482±0.021、0.447±0.021、0.491±0.022)与加氟组、氟+铝组(0.562±0.025、0.591±0.020)比较,差异有统计学意义(P均<0.05);对照组iNOS蛋白表达阳性细胞主要分布在关节表层,各实验组iNOS阳性细胞在关节面表层、中层均有分布.结论 茶多酚能通过清除氧自由基、提高机体总抗氧化能力、减少脂质过氧化产物等抗氧化作用减轻饮茶型氟中毒引起的大鼠氧化应激损伤,对饮茶型氟中毒有一定的保护作用.     

Fine structure of rat islet cell tumors induced by streptozotocin and nicotinamide

Summary Young male Holtzman rats were injected intravenously with 50 mg/kg of Streptozotocin, preceded and followed by a single intraperitoneal injection of 350 mg/kg of nicotinamide, according to the method of Rakieten et al. [16]. After 245 to 323 days, 27 pancreatic islet cell tumors measuring up to 0.6 cm were demonstrable in 20 of 41 rats so treated; they were solitary in 15 and multiple (two or three neoplasms each) in five animals. It was not possible to distinguish between tumor-bearing and tumor-free rats on the basis of periodic blood sugar determinations and serum insulin assays. Mean insulin concentration in grossly tumor-free pancreatic specimens was 0.661 units of insulin/g of wet tissue, but amounted to 5.385 units/g in specimens containing tumor. The islet cell tumors were rounded and well delineated. They were located in all parts of the pancreas. In general, their cells stained deeply with aldehyde-fuchsin. Ultra-structurally, most tumors consisted of well granulated B cells. A or D cells were not encountered while occasional EC cells were identified. Nucleoli were frequently prominent. Some necrotic B cells and others with few or unusually small secretory granules were present. Extravasated erythrocytes as well as hemosiderin deposits were seen in many tumors, and tumor cell particles were occasionally noted within the lumina of capillaries. Distant metastases were not demonstrable in this group of animals.Supported by a grant from the National Institutes of health, No. A.2203Presented at the Eighth Congress of the International Diabetes Federation, Brussels, Belgium, June, 1973     

Mitochondrial oxidative damage and apoptosis induced by high glucose through Rho kinase signal pathway in renal tubular epithelial cells

Objective: To investigate the role of oxidative stress in human renal tubular epithelial cells(HK-2) induced by high glucose and the underlying signal pathway in vitro.Methods:MYPT1,pro-caspase-3,PGC-1α,and Drpl protein expressions were measured by Western blot.MnSOD2,Drp1 and PGC-1α mRNA expressions were detected by real time PCR.Results: Results showed that high glucose significantly up-regulated the protein expressions of MYPT1,pro-caspase-3 and the mRNA expression of MnSOD2 in HK-2 cells; while Rho kinase inhibitor fasudil and ROCK1 siRNA inhibited protein expressions of pro-caspase-3 and the mRNA expression of MnSOD2 in HK-2 cells induced by high glucose.Importantly,fasudil and ROCK1 siRNA markedly inhibited the expressions of mitochondrial motor proteins Drp1 and mitochondrial gene PGC-la in HK-2 cell=s induced by high glucose.Conclusions: Our findings suggest that Rho kinase signal pathway is involved in mitochondrial oxidative damage and apoptosis in high glucose-induced renal tubular epithelial cells by regulating mitochondrial motor proteins Drp1 and mitochondrial gene PGC-1α.Targeting Rho kinase signal pathway might be a potential strategy for the treatment of diabetic nephropathy.     

N-acetylcysteine attenuates renal alterations induced by senescence in the rat

The aim of this study was to evaluate the effects of N-acetylcysteine (NAC) on renal function, as well as on sodium and water transporters, in the kidneys of aged rats. Normal, 8-month-old male Wistar rats were treated (n = 6) or not (n = 6) with NAC (600 mg/L in drinking water) and followed for 16 months. At the end of the follow-up period, we determined inulin clearance, serum thiobarbituric acid reactive substances (TBARS), serum cholesterol, and urinary phosphate excretion. In addition, we performed immunohistochemical staining for p53 and for ED-1-positive cells (macrophages/monocytes), together with Western blotting of kidney tissue for NKCC2, aquaporin 2 (AQP2), urea transporter A1 (UT-A1) and Klotho protein. At baseline, the two groups were similar in terms of creatinine clearance, proteinuria, cholesterol, and TBARS. At the end of the follow-up period, NAC-treated rats presented greater inulin clearance and reduced proteinuria, as well as lower serum cholesterol, serum TBARS, and urinary phosphate excretion, in comparison with untreated rats. In addition, NAC-treated rats showed upregulated expression of NKCC2, AQP2, and UT-A1; elevated Klotho protein expression, low p53 expression, and few ED-1 positive cells. In conclusion, we attribute these beneficial effects of NAC (the significant improvements in inulin clearance and in the expression of NKCC2, AQP2, and UT-A1) to its ability to decrease oxidative stress, inhibit p53 expression, minimize kidney inflammation, and stimulate Klotho expression.     

猪胰岛与大鼠睾丸支持细胞共同移植对糖尿病大鼠胰岛生长的影响

目的　研究胰岛异种移植的方法。　方法　用SD大鼠睾丸支持细胞 (Sertoli细胞 )与新生猪胰岛样细胞团 (ICCs)共同培养后进行异种移植。　结果　对照组胰岛细胞存活率及存活时间分别为 (63 .6%± 4.2 %和 3 .4d± 1.2d) ,较共同培养组 (87.2 %± 2 .7%和 13 .5d± 4.6d)显著为低(P <0 .0 1) ;对照组大部分胰岛细胞超微结构破坏 ,而共同培养组胰岛细胞超微结构基本正常 ;对照组胰岛素 2 4h累积分泌量和对葡萄糖刺激的反应性下降 ,共同培养组胰岛素分泌量始终处于高水平状态 (P <0 .0 1)。　结论　猪胰岛细胞与Sertoli细胞共同培养移植可以促进胰岛生长 ,明显延长胰岛移植物的存活时间     

Melatonin protects against endosulfan-induced oxidative tissue damage in rats

Abstract:  Endosulfan is a chlorinated cyclodiene insecticide which induces oxidative stress. In this study, we investigated the possible protective effect of melatonin, an antioxidant agent, against endosulfan (Endo)-induced toxicity in rats. Wistar albino rats (n = 8) were administered endosulfan (22 mg/kg/day orally) followed by either saline (Endo group) or melatonin (10 mg/kg/day, Endo + Mel group) for 5 days. In other rats, saline (control group) or melatonin (10 mg/kg/day, Mel group) was injected for 5 days, following corn oil administration (vehicle of endosulfan). Measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content were performed in liver and kidney. Furthermore, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine levels, lactate dehydrogenase (LDH) activity were measured in the serum samples, while tumor necrosis factor-α (TNF-α), interleukin-β (IL-β) and total antioxidant capacity (AOC) were assayed in plasma samples. Endosulfan administration caused a significant decrease in tissue GSH and plasma AOC, which was accompanied with significant rises in tissue MDA and collagen levels and MPO activity. Moreover, the proinflammatory mediators (TNF-α and IL-β), LDH activity, AST, ALT, creatinine and BUN levels were significantly elevated in the endosulfan-treated rats. On the other hand, melatonin treatment reversed all these biochemical alterations induced by endosulfan. Our results suggest that oxidative mechanisms play an important role in endosulfan-induced tissue damage and melatonin, by inhibiting neutrophil infiltration, balancing oxidant–antioxidant status and regulating the generation of inflammatory mediators, ameliorates oxidative organ injury as a result of endosulfan toxicity.     

Microcirculatory responses to estradiol benzoate in chronic liver damage induced by carbon tetrachloride in the rat

Microcirculatory responses to estradiol benzoate (ES) under condition of chronic liver damage induced by long-term administration of carbon tetrachloride (CCl4) was investigated in the rat. One hundred and five male rats were divided into the following groups receiving 0.1 mg/100 g body weight ES injected intraperitoneally 5 times per week: controls, exposed to CCl4 alone; rats treated with ES from the fourth week of CCl4 exposure; animals treated with ES from the 11th week of CCl4 exposure. In rats receiving CCl4 alone, liver cirrhosis was induced by 10 consecutive weeks of exposure. Microangiograms of the liver demonstrated conspicuous rarefaction of the vascular tree. On the other hand, animals treated with ES had neither atrophic liver nor rarefaction of the intrahepatic vascular tree. ES produced also intrahepatic neovascular proliferation in the cirrhotic liver. After long-term CCl4 administration, ES treated rats had extremely enlarged nodules with tumor-stain like findings, giving rise to a structure differing from hepatocellular carcinoma which latter generally displays a broom-swept appearance. It is concluded that in providing potent angiogenesis in the liver, ES protects the liver against microcirculatory dearangement and parenchymal damage induced by CCl4.     

Failure of carboxymethylglucan to inhibit oxidative DNA damage induced by hydroxyl radicals or singlet oxygen

The ability of carboxymethylglucan (CMG), a high molecular water-soluble derivative of glucan, was evaluated to act as a scavenger of reactive oxygen species. Hydrogen peroxide and methylene blue plus visible light, well-defined oxidant factors, were used as a model agents for induction ofoxidative DNA damage in CaCo-2 cells. Both hydrogen peroxide and visible light gave rise to dose-dependent increase of DNA damage mediated by hydroxyl radicals (*OH) or singlet oxygen (1O2), respectively. While DNA lesions generated by hydrogen peroxide dominated by strand breakage, exposure of CaCo-2 cells to visible light led mainly to base modifications sensitive to formamidopyrimidine DNA-glycosylase (Fpg). Neither CMG nor ascorbic acid, a known antioxidant, induced any DNA damage in CaCo-2 cells. Pretreatment of cells with ascorbic acid prior to H2O2 or visible light exposure resulted into statistically significant reduction of DNA lesions induced by particular agent. However, pretreatment of CaCo-2 cells with CMG in concentration range from 0.01 microM to 1 microM reduced neither the level of strand breaks induced by hydrogen peroxide nor the number of Fpg-sensitive base modifications generated by visible light.     

Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away

A central tenet in understanding the biological effects of ionizing radiation has been that the initially affected cells were directly damaged by the radiation. By contrast, evidence has emerged concerning "bystander" responses involving damage to nearby cells that were not themselves directly traversed by the radiation. These long-range effects are of interest both mechanistically and for assessing risks from low-dose exposures, where only a small proportion of cells are directly hit. Bystander effects have been observed largely by using single-cell in vitro systems that do not have realistic multicellular morphology; no studies have as yet been reported in three-dimensional, normal human tissue. Given that the bystander phenomenon must involve cell-to-cell interactions, the relevance of such single-cell in vitro studies is questionable, and thus the significance of bystander responses for human health has remained unclear. Here, we describe bystander responses in a three-dimensional, normal human-tissue system. Endpoints were induction of micronucleated and apoptotic cells. A charged-particle microbeam was used, allowing irradiation of cells in defined locations in the tissue yet guaranteeing that no cells located more than a few micrometers away receive any radiation exposure. Unirradiated cells up to 1 mm distant from irradiated cells showed a significant enhancement in effect over background, with an average increase in effect of 1.7-fold for micronuclei and 2.8-fold for apoptosis. The surprisingly long range of bystander signals in human tissue suggests that bystander responses may be important in extrapolating radiation risk estimates from epidemiologically accessible doses down to very low doses where nonhit bystander cells will predominate.     

Melatonin ameliorates oxidative organ damage induced by acute intra-abdominal compartment syndrome in rats

Acutely increased intra-abdominal pressure (IAP) can lead to multiple organ failure. As blood flow to intra-abdominal organs is reduced by high venous resistance, ischemia-reperfusion (I/R) injury plays an important role in the pathogenesis of abdominal compartment syndrome (ACS) following IAP. Melatonin, a secretory product of the pineal gland, is known to have free radical scavenging and antioxidative properties in several oxidative processes. The objective of this study was to examine the potential protective properties of melatonin on the oxidative organ damage in a rat model of ACS. Under ketamine anesthesia, an arterial catheter was inserted intraperioneally (i.p.) and using an aneroid manometer connected to the catheter, IAP was kept at 20 mmHg (ischemia group; I) for 1 hr. In the ischemia/reperfusion (I/R) group, pressure applied for an hour was decompressed and a 1-hr reperfusion period was allowed. In another IR group, melatonin was administered (10 mg/kg, i.p.) immediately before the decompression of IAP. The results demonstrate that tissue levels of malondialdehyde (MDA) and myeloperoxidase activity (MPO; index of tissue neutrophil infiltration) were elevated, while glutathione (GSH; a key to antioxidant) levels were reduced in both I and I/R groups (P < 0.05-0.001). Melatonin treatment in I/R rats reversed these changes (P < 0.01-0.001). Moreover, melatonin given to the I/R group reduced the elevations in serum aspartate aminotransferase, alanine aminotransferase and blood urea nitrogen levels and abolished the increase in serum creatinine levels. Our results indicate that melatonin, because of antioxidant and free radical scavenging properties, ameliorates reperfusion-induced oxidative organ damage. In conclusion, the results of the present study suggest that the therapeutic value of melatonin as a 'reperfusion injury-limiting' agent must be considered in ACS.     

A phytochemical approach to experimental metabolic syndrome-associated renal damage and oxidative stress

The aim of this study was to evaluate the effect of DTS-phytocompound on oxidant-antioxidant balance and protein damage in the kidneys of rats administered high doses of fructose. Adult male Wistar rats were divided into four groups. Group A received a control diet, whereas groups B and C were fed a high-fructose diet (60 g/100 g), the latter with additional DTS (50 mg/kg per day) for 60 days. Lipo- and nitro-peroxidation together with α-smooth muscle actin (α-SMA) expression in the glomerular and interstitial tissue of the kidneys were measured after 60 days. Fructose-fed rats showed significantly higher lipoperoxidation, 2,4-dinitrophenol and 3-nitrotyrosine protein adducts, and upregulation of α-SMA in the kidney. DTS significantly decreased such redox unbalance in renal tissue, while partially downregulating α-SMA (p<0.01). These data suggest the potential clinical benefit of DTS in protecting the kidneys from metabolic syndrome-associated changes; gender-related analysis is under way.