Vitamin C protects rat cerebellum and encephalon from oxidative stress following exposure to radiofrequency wave generated by a BTS antenna model

Radio frequency wave (RFW) generated by base transceiver station has been reported to produce deleterious effects on the central nervous system function, possibly through oxidative stress. This study was conducted to evaluate the effect of RFW-induced oxidative stress in the cerebellum and encephalon and the prophylactic effect of vitamin C on theses tissues by measuring the antioxidant enzymes activity, including: glutathione peroxidase, superoxide dismutase, catalase, and malondialdehyde (MDA). Thirty-two adult male Sprague-Dawley rats were randomly divided into four equal groups. The control group; the control-vitamin C group received L-ascorbic acid (200?mg/kg of body weight/day by gavage) for 45 days. The RFW group was exposed to RFW and the RFW+ vitamin C group was exposed to RFW and received vitamin C. At the end of the experiment, all groups were killed and encephalon and cerebellum of all rats were removed and stored at ?70?°C for measurement of antioxidant enzymes activity and MDA. The results indicate that exposure to RFW in the test group decreased antioxidant enzymes activity and increased MDA compared with the control groups (p?p?相似文献   

Vitamin C coadministration augments bisphenol A,nonylphenol, and octylphenol induced oxidative damage on kidney of rats

The aim of this study was to investigate whether bisphenol A (BPA), nonylphenol (NP), and octylphenol (OP) induce oxidative stress on the kidney tissue of male rats and whether coadministration of vitamin C, an antioxidant, can prevent any possible oxidative stress. The Wistar male rats were divided into seven groups, including control, BPA, NP, OP, BPA+C, NP + C, OP +C. BPA, NP, and OP (25 mg/kg/day) was administered alone; vitamin C (60 mg/kg/day) was administered along with BPA, OP, and NP to the rats for 50 days. There was a decrease in serum concentration of blood urea nitrogen (BUN) in NP and OP groups compared with control group. Vitamin C coadministration with BPA, NP, and OP did not produce significant increase in BUN concentration in BPA +C, NP+ C, and OP + C group as compared with BPA, NP, and OP groups, respectively. The lowest serum creatinine activity and the highest lactate dehydrogenase (LDH) activity was present in kidney of BPA+C, NP+C and OP+C groups compared with BPA, NP, and OP groups. The malondialdehyde (MDA) levels were significantly higher while glutathione (GSH) levels were lower in treatment groups than controls. Furthermore, an increase was observed in MDA levels whereas a decrease was observed in GSH levels in BPA+ C, NP + C, and OP+ C groups compared with BPA, NP, and OP groups, respectively. These finding are in accordance with immunohistochemical staining of MDA and GSH. Histopathological examination of the kidneys of rats in BPA, OP, NP, BPA+ C, NP + C, and OP+ C groups revealed necrotic lesions, congestion, and mononuclear cell infiltration. In conclusion BPA, NP, and OP might induce oxidative damage in kidney of rats. In addition, coadministration of vitamin C with BPA, NP, and OP to male rats augments this damage in the kidney of male rats. © 2009 Wiley Periodicals, Inc. Environ Toxicol, 2011.     

Protective effects of vitamins C and E against endometrial damage and oxidative stress in fluoride intoxication

1. Fluoride (F) is an essential trace element that has protective effects against bone mineral loss. However, it becomes toxic at higher doses and induces some adverse effects on a number of physiological functions, including reproduction. The aims of this study were to examine F-induced oxidative stress that promotes production of reactive oxygen species (ROS) and to investigate the role of vitamins C and E against possible F-induced endometrial impairment in rats. 2. Rats were divided into three groups: control, F and F plus vitamins. The F group was given 100 mg/L orally for 60 days. Combined vitamins were also administered orally. Fluoride administration to control rats significantly increased endometrial malondialdehyde (MDA) but decreased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities. Endometrial glandular and stromal apoptosis were investigated by DNA nick end-labelling (TUNEL) method on each sample and the mean endometrial apoptotic index (AI) was calculated. 3. Vitamin administration with F treatment caused endometrial MDA to decrease, but SOD, GSH-Px and CAT activities to increase, all to significant levels. Vitamins showed a histopathological protection against F-induced endometrial damage. There was a significant difference in the AI between the groups. Lymphocyte and eosinophil infiltration in stroma in F-treated rats were more than those in the control and F + Vit groups. 4. It can be concluded that oxidative endometrial damage plays an important role in F-induced endometrial toxicity, and the modulation of oxidative stress with vitamins reduces F-induced endometrial damage both at the biochemical and histological levels.     

镉所致肾毒性及氧化性损害机制的研究

目的探讨氯化镉(CdCl2)引起肾脏毒性的氧化性损害机制,为防制镉危害提供实验依据。方法雄性SD大鼠随机分为4组,每组4只,体重200～260g。对照组腹腔内注射生理盐水,染镉组连续3d分别腹腔注射1.25、2.5和5mg/kg的CdCl2溶液。测定体重变化、肾脏系数、血清尿素氮(BUN)和肾皮质脂质过氧化产物丙二醛(MDA)含量,苏木素-伊红(HE)染色观察肾组织形态学,免疫组化的方法检测肾组织中8-羟基脱氧鸟苷(8-OhdG)的表达。结果CdCl2(2.5mg/kg,5mg/kg)可引起明显的肾脏毒性。表现为体重降低,BUN水平升高,肾脏系数升高;组织形态学观察可见肾毒性急性肾小管损害表现。肾皮质匀浆MDA水平升高(P<0.05)。免疫组化结果显示各实验组大鼠肾组织中可检出氧化损伤标志物8-OhdG。结论CdCl2所致大鼠氧化性损伤可能是其肾脏毒性的机制之一。     

维生素 C 联合维生素 E 对 COPD 患者氧化应激的影响

目的：探讨维生素C联合维生素 E对COPD患者氧化应激的影响。方法从贵阳医学院附属医院2011年6月6日至2014年3月20日住院患者中选择符合条件的30例COPD患者将其作为实验组,在予以COPD常规治疗方法的基础上加用维生素C及维生素E治疗10 d（维生素C注射液2．0 g＋NS 250 mL ,1次／d静滴,疗程10 d;维生素E胶丸100 mg ,1次／d口服,疗程10 d）。另外30例患者作为对照组仅予以COPD常规治疗,观察并比较两组在治疗前后体内SOD与MDA变化。结果无论实验组还是对照组在治疗前血清MDA及SOD水平均差异均有统计学意义,实验组在使用维生素C、E治疗后体内SOD及MDA水平与未使用维C及维E的对照组治疗后体内SOD及MDA水平比较均有差异性,且差异有统计学意义（P＜0．05）。结论维生素C联合维生素E治疗能显著改善慢性阻塞性肺疾病患者体内氧化应激水平,维持体内氧化／抗氧化水平的平衡。     

维生素C对顺铂所致大鼠肾损伤的保护作用

目的研究维生素C（Vit C）对顺铂所致肾损伤的保护作用,并探讨其可能的机制。方法将40只成年雌性SD大鼠按体重分成5组,分别为正常对照组（A组,生理盐水）、Vit C对照组（B组,500mg／kg）、顺铂化疗模型组（C组,6mg／kg）、顺铂（6mg／kg）＋Vit C（50mg／kg或500mg／kg）干预组（D1组及D2组）。腹腔注射Vit C进行前、中、后期全程保护,并于顺铂给药5d后采血处死动物,测定血清尿素氮（BUN）、肌酐（Cr）、肾皮质匀浆丙二醛（MDA）含量及谷胱甘肽过氧化物酶（GSH—Px）、超氧化物歧化酶（SOD）活力的变化。结果与C组相比,D1组及D2组的血清Cr及BUN、肾皮质匀浆MDA含量明显下降（P〈0．01或P〈0．05）,GSH—Px和SOD活力略有增加。结论Vit C可以减轻顺铂所致肾损伤,作用机制可能与其抗氧化作用和清除自由基活性密切相关。     

Fipronil induced oxidative stress involves alterations in SOD1 and catalase gene expression in male mice liver: Protection by vitamins E and C

In the present investigation, hepatic oxidative stress induced by fipronil was evaluated in male mice. We also investigated whether pretreatment with antioxidant vitamins E and C could protect mice against these effects. Several studies conducted in cell lines have shown fipronil as a potent oxidant; however, no information is available regarding its oxidative stress inducing potential in an animal model. Out of 8 mice groups, fipronil was administered to three groups at low, medium, and high dose based on its oral LD₅₀ (2.5, 5, and 10 mg/kg)_. All three doses of fipronil caused a significant increase in the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) level with concomitant increase in the absolute and relative weight of liver. High dose of fipronil caused significant down‐regulation in the hepatic mRNA expression of superoxide dismutase 1 (SOD1) and catalase (0.412 ± 0.01 and 0.376 ± 0.05‐fold, respectively) as well as an increase in the lipid peroxidation (LPO). Also, decrease in the activity of antioxidant enzymes; SOD, catalase, and glutathione‐S‐transferase (GST) and the content of nonantioxidant enzymes; glutathione and total thiol were recorded. Histopathological examination of liver revealed dose dependant changes such as severe fatty degeneration and vacuolation leading to hepatocellular necrosis. Prior administration of vitamin E or vitamin C against fipronil high dose caused decrease in lipid peroxidation and increased activity of antioxidant enzymes. Severe reduction observed in functional activities of antioxidant enzymes was aptly substantiated by down‐regulation seen in their relative mRNA expression. Thus results of the present study imply that liver is an important target organ for fipronil and similar to in vitro reports, it induces oxidative stress in the mice liver, which in turn could be responsible for its hepatotoxic nature. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1147–1158, 2016.     

Hepatotoxicity and nephrotoxicity in rats induced by carbon tetrachloride and the protective effects of Teucrium polium and vitamin C

This work investigated the protective effects of Teucrium polium (T. polium) and vitamin C (Vit C) against carbon tetrachloride (CCl₄) induced hepatotoxicity and nephrotoxicity in rats. T. polium reduced the Fer reduced antioxidant power (FRAP) (IC₅₀?=?0.89?mg/ml) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) (IC₅₀?=?0.049 µg/ml) than Vit C, FRAP (IC₅₀?=?0.71?mg/ml) and DPPH (IC₅₀?=?0.029 µg/ml). Male albino Wistar rats were divided into six groups: Group I was used as controls, Group II received CCl₄ in olive oil (0.5?ml/kg) by gavage, Group III received CCl₄ in olive oil (0.5?ml/kg) by gavage after 3 d of receiving T. polium (5?g/l), orally, Group IV received T. polium (5?g/l) alone, by gavage, for 7 d, Group V received CCl₄ in olive oil (0.5?ml/kg) by gavage after 3 d of receiving Vit C (250?mg/kg) by gavage and Group VI received Vit C (250?mg/kg) alone by gavage. CCl₄ showed an increase of serum hepatic and renal markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine. Moreover, we noted an increase of lipid peroxidations and a decrease in antioxidants enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) of CCl₄ rats compared to controls. The pretreatment with (200?mg/kg) of T. polium and with Vit C (250?mg/kg) by gavage, for 7 d, displayed their ability to protect against oxidative damage and biochemical changes induced by CCl₄. Our results were in accordance with histopathological observations.     

高效液相法测定二维亚铁颗粒中的维生素C含量

目的:建立HPLC法测定二维亚铁颗粒中的有效成分维生素C的含量。方法:采用watersC18色谱柱(4.6mm×250mm,5μm),流动相为0.02mol/LKH2PO4溶液(pH6.0)-乙腈(40:60);柱温30℃,流速为1.0ml/min,波长为255mm。结果:维生素C在8.84～88.4μg/ml的浓度范围内有良好的线性关系(r=0.998);平均回收率为99.1%,RSD为1.1%。结论:此法简便、快速、准确,适用于维生素C的含量测定。     

Vitamin C prevents memory impairment induced by waterpipe smoke: role of oxidative stress

Waterpipe tobacco smoking (WTS) was previously shown to be associated with memory deficits, which were related to oxidative stress. Vitamin C (VitC) has established antioxidant properties against memory deficits associated with several diseases and conditions. In this study, the potential protective effect of VitC on memory impairment induced by WTS exposure was evaluated in a rat model. VitC was administered to animals via oral gavage (100?mg/kg/day, 6?days a week for 4 weeks). At the same period, animals were exposed to WTS for one hour/day, 6?days a week for 4?weeks. Using radial arm water maze (RAWM), behavioral tests were conducted to evaluate the spatial learning and memory. In addition, hippocampal levels of oxidative stress biomarkers were analyzed. WTS exposure impaired both short- and long-term memory (p?p?p?p?>?.05). In conclusion, WTS resulted in inducing memory impairment, which was prevented by VitC administration. This could be related to preserving hippocampus antioxidant mechanisms by VitC during WTS exposure.     

Therapeutic role of quercetin on oxidative damage induced by acrylamide in rat brain

Context Quercetin (QE), a bioflavonoid present abundantly in fruits and vegetables, has been reported to possess antioxidant properties. Acrylamide (ACR) is formed in foods during cooking and is known to be neurotoxic.

Objective The present study was designed to evaluate the protective effect of QE against neurotoxicity induced by ACR.

Materials and methods Four groups of Wistar rats consisting of six rats each: (i) control group; (ii) acrylamide treated group (50?mg/kg body weight as single dose); (iii) quercetin group: rats were treated intraperitoneally (i.p.) with QE (10?mg/kg body weight alone every day for 5 d); (iv) quercetin?+?acrylamide group: quercetin (10?mg/kg bw) was given i.p. every day for 5 d followed by acrylamide i.p. injection (50?mg/kg bw) on fifth day (single dose). Rats were killed after 48?h.

Results Administration of ACR (50?mg/kg bw) in Wistar rats resulted in significant increase of dopamine, interferon-γ and 8-hydroxyguanosine with concomitant decrease of serotonin (p?<?0.001) in the rat brain. Treatment of rats with QE intraperitonealy (10?mg/kg body weight) before ACR assault resulted in the diminution of ACR-mediated neurotoxicity as evident from decreased levels of dopamine, interferon-γ (p?<?0.001) and 8-hydroxyguanosine with concomitant restoration of serotonin levels (p?<?0.001).

Discussion and conclusion On the basis of the above results, the present study suggests that quercetin may be a potential therapeutic agent for restoration of oxidative damage to neurons.     

Vitamin B complex mitigates cardiac dysfunction in high‐methionine diet‐induced hyperhomocysteinemia

This research is designed to test the hypothesis that elevated homocysteine (Hcy) levels in vivo, caused by a deficit in vitamin B complex, promote changes in cardiac function and redox status that lead to heart failure. In order to conduct the study, we used adult male Wistar albino rats (n = 30; 4 weeks old; 100 ± 15 g body weight). Hyperhomocysteinaemia (HHcy) in these animals was achieved by dietary manipulation. For 4 weeks, the animals were fed with a standard rodent chow (control, CF), a diet enriched in methionine with no deficiency in B vitamins (i.e., folic acid, B6 and B12) (HMNV) or a diet enriched in methionine and deficient in B vitamins (HMLV). After 28 days of dietary manipulation, all animals were killed. The rat hearts were isolated and retrogradely perfused according to the Langendorff technique at a gradually increasing perfusion pressure. We found a negative correlation between elevated serum Hcy and total body and heart weight. The maximum rate of left ventricular pressure development was significantly increased in the HMNV group compared with in the other groups. Systolic left ventricular pressure was significantly changed in all groups. HHcy induces remodelling of the cardiac tissues, as moderate HHcy is associated with more prominent interstitial and perivascular fibrosis. Our results suggest that a high methionine diet without vitamin B complex causes profound negative effects associated with HHcy.     

Folic acid or combination of folic acid and vitamin B(12) prevents short-term arsenic trioxide-induced systemic and mitochondrial dysfunction and DNA damage

The effect of folic acid and folic acid + vitamin B(12) supplementation upon short-term arsenic-induced systemic and pancreatic islet cell mitochondria oxidative stress was investigated in male rats. Arsenic trioxide was administered orally at a dose of 3 mg kg body weight(-1) day(-1) for 30 days, and folic acid and vitamin B(12) were administered at a dose of 36 and 0.63 microg kg body weight(-1) day(-1), respectively, for 30 days. Compared to control, arsenic-treated group showed a significant increase in the levels of systemic oxidative markers, malondialdehyde (MDA), nitric oxide (NO), and hydroxyl radical (OH(-)) formation, which were found decreased significantly after supplementation either with folic acid or a combination of folic acid + vitamin B(12). Similar supplementations were found effective against arsenic-induced oxidative marker changes (MDA, NO, and OH(-)) in pancreatic islet cell mitochondria. Also, low activities of antioxidant defense enzymes such as superoxide dismutase and catalase, and level of antioxidant glutathione, all could regain significantly on supplementations both against systemic and islet cell mitochondria oxidative stress. Results of agarose-gel electrophoresis of DNA from lymphocytes and islet cells of arsenic-exposed rats showed DNA smearing, which could be reduced with simultaneous administration either with folic acid or a combination of folic acid + vitamin B(12). Significantly, similar supplementations were found effective in increasing the urinary clearance of arsenic. Together, these results indicate that folic acid and vitamin B(12) may be effective to reduce the arsenic-induced damage at molecular target level.     

Diphenyl diselenide prevents oxidative damage induced by cigarette smoke exposure in lung of rat pups

The effect of cigarette smoke exposure on lungs of rat pups was evaluated. Animals were exposed to passive cigarette smoke during 3 weeks and a number of toxicological parameters in lung of pups were examined, such as lipid peroxidation, δ-aminolevulic acid dehydratase (δ-ALA-D) activity, components of the enzymatic antioxidant defenses (superoxide dismutase (SOD) and catalase activities) and non-enzymatic antioxidant defenses (Vitamin C and non-protein thiol (NPSH) levels). Furthermore, a possible protective effect of diphenyl diselenide, (PhSe)₂, was studied. The results demonstrated an increase in lipid peroxidation, an inhibition of δ-ALA-D activity, a reduction of Vitamin C and NPSH levels induced by cigarette smoke exposure, indicating damage in lungs of rat pups. Oral administration of (PhSe)₂ (0.5 mg/kg) restored TBARS levels, non-enzymatic antioxidant defenses and activity of δ-ALA-D. These results indicated that exposure to cigarette smoke enhanced oxidative stress, thereby disturbing the tissue defense system. (PhSe)₂ protected against oxidative damage induced by cigarette smoke exposure in lung of rat pups.     

Angiotensin-converting enzyme inhibitor prevents oxidative stress,inflammation, and fibrosis in carbon tetrachloride-treated rat liver

Hepatic fibrosis is a common feature of chronic liver injury, and the involvement of angiotensin II in such process has been studied earlier. We hypothesized that anti-angiotensin II agents may be effective in preventing hepatic fibrosis. In this study, Long Evans female rats were used and divided into four groups such as Group-I, Control; Group-II, Control?+?ramipril; Group-III, CCl₄; and Group-IV, CCl_4?+_?ramipril. Group II and IV are treated with ramipril for 14 d. At the end of treatment, the livers were removed, and the level of hepatic marker enzymes (aspartate aminotransferase, Alanine aminotransferase, and alkaline phosphatase), nitric oxide, advanced protein oxidation product , catalase activity, and lipid peroxidation were determined. The degree of fibrosis was evaluated through histopathological staining with Sirius red and trichrome milligan staining. Carbon-tetrachloride (CCl₄) administration in rats developed hepatic dysfunction and raised the hepatic marker enzymes activities significantly. CCl₄ administration in rats also produced oxidative stress, inflammation, and fibrosis in liver. Furthermore, angiotensinogen-inhibitor ramipril normalized the hepatic enzymes activities and improved the antioxidant enzyme catalase activity. Moreover, ramipril treatment ameliorated lipid peroxidation and hepatic inflammation in CCl₄-treated rats. Ramipril treatment also significantly reduced hepatic fibrosis in CCl₄-administered rats. In conclusion, our investigation suggests that the antifibrotic effect of ramipril may be attributed to inhibition of angiotensin-II mediated oxidative stress and inflammation in liver CCl₄-administered rats.     

Malathion-induced oxidative stress in human erythrocytes and the protective effect of vitamins C and E in vitro

Malathion is an organophosphate (OP) pesticide that has been shown to induce oxidative stress in erythrocytes through the generation of free radicals and alteration of the cellular antioxidant defense system. We examined the effect of several different doses of malathion (25, 75, 200 microM), or malathion in combination with vitamin C (VC; 10 microM) or vitamin E (VE; 30 microM), on the levels of malondialdehyde (MDA), and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in human erythrocytes in vitro. Erythrocytes were incubated under various treatment conditions (malathion alone, vitamins alone, or malathion plus vitamin) at 37 degrees C for 60 min, and the levels of MDA, and SOD, CAT and GPx activities, were determined. Treatment with malathion alone increased the levels of MDA and decreased SOD, CAT, and GPx activities in erythrocytes (P < 0.05). There were no statistical differences among VC-treated, VE-treated, or VC + VE-treated erythrocyes, as compared with nontreated control cells. Treatment of cells with malathion + VC, malathion + VE, or a combination of all three agents prevented malathion-induced changes in antioxidant enzyme activity and lipid peroxidation. However, this effect was seen only at low concentrations of malathion (25 and 75 microM), and the combination of VC + VE had a more protective effect than VC or VE alone. These results indicated that the presence of vitamins at concentrations that are similar to the levels found in plasma have no effect on malathion-induced toxicity in erythrocytes at a concentration of malathion (200 microM) that is typically used in pesticides.     

Benidipine prevents oxidative stress,inflammatory changes and apoptosis related myofibril damage in isoproterenol-induced myocardial infarction in rats

Abstract

Objective: The effects of benidipine on oxidative stress and myocardial apoptosis were assessed in isoproterenol (ISO)-induced myocardial infarction (MI) in wistar rats.

Materials and method: Animals were pretreated with benidipine (1, 3, 10?μg/kg/day Body weight) intravenously for a period of 28 days. After pretreatment, ISO (85?mg/kg Body weight, subcutaneous) was injected in rats at an interval of 24?h to induce MI. Myocardial oxidative stress, cardiac biomarkers, apoptosis, inflammatory mediators, and ultrastructural architecture of the cardiac tissue were assessed in ISO-induced MI in rats.

Result: Significant variation in the level of TBA, antioxidant enzymes (GSH, CAT, SOD, GPx, GRx, GST) in myocardium, cardiac biomarkers (CK-MB, LDH) in serum, Caspase-3, C-reactive protein (CRP), and alteration in ultrastructural architecture of cardiac tissue confirmed the cardiotoxicity induced by ISO. Pretreatment with benidipine preserved the lipid peroxide and antioxidant enzymes, and furthermore showed maintained levels of myocardial biomarker, CRP and caspase-3. Ultrastructure architecture of cardiac tissue was also found to be well preserved.

Conclusion: The present study suggested cardioprotective effect of benidipine which may possibly be due to its antioxidant activity and antiapoptotic nature.     

Endothelium-dependent contractions and endothelial dysfunction in human hypertension

The endothelium is a crucial regulator of vascular physiology, producing in healthy conditions several substances with a potent antiatherosclerotic properties. Accordingly, the presence of endothelial dysfunction is associated with subclinical atherosclerosis and with an increased future risk of cardiovascular events. A large body of evidence supports the fundamental role of nitric oxide (NO) as the main endothelium-derived relaxing factor. However, in the presence of pathological conditions, such as hypertension, endothelial cells, in response to a number of agents and physical stimuli, become also a source of endothelium-derived contracting factors (EDCFs), including endothelins and angiotensin II and particularly cyclooxygenase-derived prostanoids and superoxide anions. These latter were at first identified as responsible for impaired endothelium-dependent vasodilation in patients with essential hypertension. However, cyclooxygenase-dependent EDCFs production is characteristic of the aging process, and essential hypertension seems to only anticipate the phenomenon. It is worth noting that both in aging and hypertension EDCF production is associated with a parallel decrease in NO availability, suggesting that this substance could be oxygen free radicals themselves. Accordingly, in hypertension both indomethacin, a cyclooxygenase inhibitor, and vitamin C, an antioxidant, increase the vasodilation to acetylcholine by restoring NO availability. In conclusion, hypertension is characterized by a decline in endothelial function, associated with a progressive decrease in NO bioavailability and increase in the production of EDCF. The mechanisms that regulate the balance between NO and EDCF, and the processes transforming the endothelium from a protective organ to a source of vasoconstrictor, proaggregatory and promitogenic mediators remain to be determined.British Journal of Pharmacology (2009) 157, 527–536; doi:10.1111/j.1476-5381.2009.00240.xThis article is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009     

Melatonin reduces oxidative damage induced by aluminium in rat kidney

We evaluated the effect of melatonin (Mel), in male Wistar rats which received aluminium (Al) lactate for 12 weeks (0.57 mg Al/100 g body weight (b.w.), i.p. three times per week). Moreover rats received Mel (10 mg/kg b.w. i.p. 5 days/weeks) for 12 weeks. At the end of the treatment water and sodium balances were studied, and nephrogenic cyclic adenosine monophosphate (cAMP) was also measured. Urinary osmolality was measured after the administration of desmopressin (vasopressin agonist) to assess concentrating capacity. Oxidative stress in renal tissue and Na⁺–K⁺ATPase and gamma-glutamyl transferase (GGT) activities in whole plasma membrane were determined. Sodium and water balances were impaired by Al. We found decreased urinary concentrating ability and nephrogenic cAMP excretion. Al increased the Na⁺–K⁺ATPase activity, and serum aldosterone concentration. Mel normalized serum aldosterone level, the Na⁺–K⁺ATPase activity and potassium urinary without improving water and sodium excretion. Mel treatment did not improve the impaired urinary concentrating ability. Al reduced the GGT activity, an effect that persists in Al⁺ Mel. Al exposure promoted oxidative stress with an increase in lipid peroxidation (LPO), and a decrease in glutathione (GSH) and glutathione peroxidase (GSH-Px) and catalase (CAT) activities. Mel markedly attenuated oxidative stress produced by Al. This may result from the higher efficacy of melatonin in scavenging various free radicals and also because of its ability in stimulating the antioxidant enzymes. However, it only reduced some alterations in the renal functions particularly related to the water and sodium excretion, which would be independent of the increased production of reactive oxygen substances.     

Edaravone attenuates brain damage in rats after acute CO poisoning through inhibiting apoptosis and oxidative stress

Acute carbon monoxide (CO) poisoning is the most common cause of death from poisoning all over the world and may result in neuropathologic and neurophysiologic changes. Acute brain damage and delayed encephalopathy are the most serious complication, yet their pathogenesis is poorly understood. The present study aimed to evaluate the neuroprotective effects of Edaravone against apoptosis and oxidative stress after acute CO poisoning. The rat model of CO poisoning was established in a hyperbaric oxygen chamber by exposed to CO. Ultrastructure changes were observed by transmission electron microscopy (TEM). TUNEL stain was used to assess apoptosis. Immunohistochemistry and immunofluorescence double stain were used to evaluate the expression levels of heme oxygenase‐1 (HO‐1) and nuclear factor erythroid 2‐related factor 2 (Nrf‐2) protein and their relationship. By dynamically monitored the carboxyhemoglobin (HbCO) level in blood, we successfully established rat model of severe CO poisoning. Ultrastructure changes, including chromatin condensation, cytoplasm dissolution, vacuoles formation, nucleus membrane and cell organelles decomposition, could be observed after CO poisoning. Edaravone could improve the ultrastructure damage. CO poisoning could induce apoptosis. Apoptotic cells were widely distributed in cortex, striatum and hippocampus. Edaravone treatment attenuated neuronal apoptosis as compared with the poisoning group (P < 0.01). Basal expressions of HO‐1 and Nrf‐2 proteins were found in normal brain tissue. CO poisoning could activate HO‐1/Nrf‐2 pathway, start oxidative stress response. After the administration of Edaravone, the expression of HO‐1 and Nrf‐2 significantly increased (P < 0.01). These findings suggest that Edaravone may inhibit apoptosis, activate the Keapl‐Nrf/ARE pathway, and thus improve the ultrastructure damage and neurophysiologic changes following acute CO poisoning. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 372–379, 2016.