Evaluation of Antioxidant Enzymes Activity and Malondialdehyde Levels in Patients With Chronic Periodontitis and Diabetes Mellitus

Background: The aim of this study is to investigate the impact of diabetes, a known risk factor for periodontitis, on activities of antioxidant enzymes superoxide dismutase (SOD), glutathione reductase (GR), and catalase (CAT) as well as levels of free radical damage marker malondialdehyde (MDA) in blood and saliva of individuals with chronic periodontitis (CP). Methods: Sixty patients with CP (30 patients with type 2 diabetes mellitus [DMCP] and 30 systemically healthy patients [CP]) and 60 periodontally healthy individuals (30 patients with type 2 diabetes mellitus and 30 systemically healthy patients [PH]) were included in this study. After clinical measurements, blood and saliva samples were collected. SOD, GR, and CAT activities in red blood cell lysate and saliva and MDA levels in plasma and saliva samples were spectrophotometrically assayed. An analysis of variance test followed by a post hoc test was used to compare the intragroup and intergroup variances among the study groups. Results: MDA levels in both the periodontitis groups were higher than in the periodontally healthy groups, but the difference between the CP and DMCP groups did not reach statistical significance (P >0.05). There was a highly significant difference between the CP and PH groups for all the enzymes studied except for SOD in blood. Only salivary SOD and GR activities were significantly different in the CP and DMCP groups. Conclusions: This study favors the role of oxidative stress in both diabetes and periodontitis. It shows that the compensatory mechanism of the body is partially collapsed because of excessive production of free radicals during periodontitis and is not able to cope with increased free radical generation attributable to diabetes, thereby worsening the situation.     

Increase of Active Oxygen in Rats after Nephrectomy is Suppressed by Ginseng Saponin

Subtotally nephrectomized rats were found to have decreased activities of superoxide dismutase (SOD), catalase and glutathione peroxidase, and spin-trapping with 5,5-dimethyl-1-pyrroline-N-oxide showed that the amount of hydroxyl radical (·OH) in the residual kidney tissue was greater than that in the normal kidney. In contrast, rats given ginseng saponin (25 mg/kg body weight) orally for 30 days after subtotal nephrectomy showed restoration of catalase activity to almost a normal level. A significant increase in SOD activity was observed. ·OH, which is highly reactive and for which there is no scavenger system in the body, was decreased markedly in kidney homogenates obtained from rats given ginseng saponin. The increased levels of uraemic toxins in the blood were also reduced in rats given ginseng saponin. These findings indicate that ginseng saponin helps to inhibit the progression of renal failure by scavenging radicals.     

Shilajit attenuates streptozotocin induced diabetes mellitus and decrease in pancreatic islet superoxide dismutase activity in rats

Diabetes mellitus was induced in male Wistar rats by the administration of streptozotocin (STZ, 45 mg/kg, s.c. on 2 consecutive days). Hyperglycaemia and superoxide dismutase activity of pancreatic islet cells was assessed on days 7, 14, 21 and 28, following STZ administration. In two other groups, shilajit (50 and 100 mg/kg, p.o.) was administered concurrently for 28 days. STZ induced significant hyperglycaemia by day 14, which increased progressively on days 21 and 28. STZ also induced a decrease in pancreatic islet cell superoxide dismutase, which was apparent by day 7 and increased progressively, thereafter on days 14, 21 and 28. Shilajit (50 and 100 mg/kg, p.o.) had no discernible per se effect on blood glucose levels in normal rats but attenuated the hyperglycaemic response of STZ from day 14 onwards, though only the effect of the higher dose was statistically significant. Similarly, both the doses of shilajit reduced the STZ-induced decrease in superoxide dismutase activity from day 14 onwards, the effect of the lower dose being statistically insignificant. The findings confirm earlier observations that STZ-induced hyperglycaemia may be the consequence of a decrease in pancreatic islet superoxide dismutase activity, leading to accumulation of free radicals and damage of the β-cells. Shilajit attenuates both these effects of STZ possibly by its action as a free radical scavenger. The findings support the postulate that shilajit can prevent maturity onset diabetes mellitus.     

活性氧、锰型超氧化物歧化酶对胃肠道肿瘤凋亡的影响

活性氧(ROS)是近年来发现的调控肿瘤凋亡的重要信号分子之一,锰型超氧化物歧化酶(MnSOD) 是真核细胞内重要的酶性自由基清除剂,胃肠道肿瘤中存在MnSOD的高表达。此文综述了活性氧及MnSOD 对肿瘤凋亡的影响及信号转导机制,并介绍了以超氧化物歧化酶(SOD)作为新靶点进行肿瘤基因治疗的最新进展。     

Sod1 integrates oxygen availability to redox regulate NADPH production and the thiol redoxome

Cu/Zn superoxide dismutase (Sod1) is a highly conserved and abundant antioxidant enzyme that detoxifies superoxide (O₂^•−) by catalyzing its conversion to dioxygen (O₂) and hydrogen peroxide (H₂O₂). Using Saccharomyces cerevisiae and mammalian cells, we discovered that a major aspect of the antioxidant function of Sod1 is to integrate O₂ availability to promote NADPH production. The mechanism involves Sod1-derived H₂O₂ oxidatively inactivating the glycolytic enzyme, GAPDH, which in turn reroutes carbohydrate flux to the oxidative phase of the pentose phosphate pathway (oxPPP) to generate NADPH. The aerobic oxidation of GAPDH is dependent on and rate-limited by Sod1. Thus, Sod1 senses O₂ via O₂^•− to balance glycolytic and oxPPP flux, through control of GAPDH activity, for adaptation to life in air. Importantly, this mechanism for Sod1 antioxidant activity requires the bulk of cellular Sod1, unlike for its role in protection against O₂^•− toxicity, which only requires <1% of total Sod1. Using mass spectrometry, we identified proteome-wide targets of Sod1-dependent redox signaling, including numerous metabolic enzymes. Altogether, Sod1-derived H₂O₂ is important for antioxidant defense and a master regulator of metabolism and the thiol redoxome.

Superoxide dismutases (SODs) serve on the frontline of defense against reactive oxygen species (ROS). SODs, which detoxify O₂^•− by catalyzing its disproportionation into O₂ and hydrogen peroxide (H₂O₂), are unique among antioxidant enzymes in that they also produce a ROS byproduct. While much is known about the necessity of scavenging O₂^•−, it is less clear what the physiological consequences of SOD-derived H₂O₂ are. Paradoxically, increased expression of Cu/Zn SOD (Sod1), which accounts for the majority of SOD activity in cells (1), is associated with reduced cellular H₂O₂ levels (2), suggesting there may be additional unknown mechanisms underlying Sod1 antioxidant activity.The cytotoxicity of O₂^•− stems from its ability to oxidize and inactivate [4Fe-4S] cluster-containing enzymes, which results in defects in metabolic pathways that utilize [4Fe-4S] proteins and Fe toxicity due to its release from damaged Fe/S clusters (3–6). The released Fe can catalyze deleterious redox reactions and, in particular, production of hydroxyl radicals (^•OH) via Haber-Weiss and Fenton reactions, which indiscriminately oxidizes lipids, proteins, and nucleic acids (4, 7). The importance of Sod1 in oxidative stress protection is underscored by reduced proliferation, decreased lifespan, and numerous metabolic defects, including cancer, when SOD1 is deleted in various cell lines and organisms (7–11). It was previously proposed that Sod1 limits steady-state H₂O₂ levels because of its ability to prevent the O₂^•−-mediated oxidation of Fe/S clusters, which results in the concomitant formation of H₂O₂ (2, 12, 13). However, since vanishingly small amounts of Sod1 (<1% of total cellular Sod1) is sufficient to protect cells against O₂^•− toxicity, including oxidative inactivation of Fe/S enzymes (14–16), any changes in Sod1 expression would not be expected to alter H₂O₂ arising from O₂^•− oxidation of Fe/S clusters. How then can Sod1, an enzyme that catalyzes H₂O₂ formation, act to reduce cellular [H₂O₂]?Two previously reported but unexplained metabolic defects in sod1Δ strains of Saccharomyces cerevisiae point to a potential role for Sod1 in regulating the production of NADPH, a key cellular reductant required for reductive biosynthesis and the reduction and regeneration of H₂O₂ scavenging thiol peroxidases (17) and catalases (18, 19). Yeast strains lacking SOD1 exhibit increased glucose consumption (20) and defects in the oxidative phase of the pentose phosphate pathway (oxPPP) (21), the primary source of NADPH. Inhibition of key rate-limiting enzymes in glycolysis—including phosphofructose kinase (22), GAPDH (23, 24), and pyruvate kinase (25, 26)—reduces glucose uptake (27–29) and increases the concentration of glucose-6-phosphate (G6P), a glycolytic intermediate that is also the substrate for the first enzyme in the oxPPP, G6P dehydrogenase (G6PDH), which in turn increases oxPPP flux and NADPH production (30–35). Taking these data together, we surmised that Sod1 negatively regulates a rate-determining enzyme in glycolysis, thereby accounting for the observed metabolic defects in glucose utilization and the oxPPP in sod1Δ cells (20, 21).GAPDH, which catalyzes a rate-determining step in glycolysis (36, 37), is very abundant (38), and contains a H₂O₂-reactive catalytic Cys (k ∼ 10² to 10³ M⁻¹s⁻¹), represents a critical redox regulated node that can toggle flux between glycolysis and the oxPPP (32). As such, we hypothesized that a novel aspect of the antioxidant activity of Sod1 is to oxidatively inactivate GAPDH using Sod1-catalyzed H₂O₂, which would in turn stimulate NADPH production via the oxPPP and enhance cellular peroxide scavenging by thiol peroxidases. This mechanism for Sod1-mediated antioxidant activity would explain a number of prior observations, including the findings that elevated Sod1 expression decreases peroxide levels and loss of SOD1 increases glucose consumption and attenuates oxPPP activity. In addition, more generally, since Sod1-derived H₂O₂ has previously been implicated in the redox regulation of other enzymes, including protein tyrosine phosphatases (39) and casein kinases (15, 16, 40), we also sought to identify proteome-wide redox targets of Sod1.In the present report we provide evidence highlighting an antioxidant function for Sod1-derived H₂O₂ in integrating O₂ availability to control NADPH production to support aerobic growth and metabolism. The mechanism involves the conversion of O₂ to O₂^•− by mitochondrial respiration and an NADPH oxidase, followed by the Sod1-catalyzed conversion of O₂^•− to H₂O₂, which in turn oxidatively inactivates GAPDH. The inhibition of GAPDH serves to reroute metabolism from glycolysis to the oxPPP in order to maintain sufficient NADPH for metabolism in air. The aerobic oxidation of GAPDH is dependent on and rate-limited by Sod1, suggesting that it provides a privileged pool of peroxides to inactivate GAPDH under physiological conditions. Finally, we revealed a larger network of cysteine-containing proteins that are oxidized in a Sod1-dependent manner using mass spectrometry-based redox proteomics approaches. Altogether, these results highlight a mechanism for O₂ sensing and adaptation, reveal an important but previously unknown antioxidant role of Sod1 that goes beyond O₂^•− scavenging to include the stimulation of aerobic NADPH production, and places Sod1 as a master regulator of proteome-wide thiol oxidation and multiple facets of metabolism.     

真菌抗氧化酶的研究进展

真菌对抗宿主的氧化损伤作用是真菌能顺利入侵宿主的一个重要因素。抗氧化酶的调节是真菌发挥抗氧化作用的重要途径之一,也是目前研究的热点。其中,抗氧化酶包括过氧化氢酶、超氧化物歧化酶、谷胱甘肽还原酶与谷胱甘肽过氧化物酶、硫氧还蛋白系统以及海藻糖酶系统。几种常见真菌的抗氧化酶及编码抗氧化酶的相关基因的研究取得了进展,包括编码过氧化氢酶的相关基因如CTT1、CATA;编码超氧化物歧化酶的SOD基因;谷胱甘肽系统相关的GRX、GST基因;编码硫氧还蛋白系统的TRX、TRR基因以及海藻糖系统相关的TPS、ATH1基因等。     

溶血磷脂酸与饮食所致高血脂幼兔主动脉壁病变发展的关系

目的探讨血浆溶血磷脂酸(LPA)水平变化与高脂喂养幼兔主动脉粥样硬化(AS)病变发展的关系。方法2月龄家兔随机分成普通饮食组(A组,n=6)与高脂喂养组(B组,n=11)。分别饲喂高脂饲料与普通饲料。动态测定血脂水平、血浆LPA水平、血清一氧化氮(NO)和丙二醛(MDA)水平及超氧化物歧化酶(SOD)活性。另于各个时间点选取B组中兔一只,处死,进行胸主动脉病理学检查。结果高脂喂养1~2周动脉内膜显示微观结构改变。脂质条纹(FS)形成于高脂喂养第4周并进行性加重。血脂水平自高脂喂养1周后即显著升高,以后进行性升高。血浆LPA水平于FS形成前期即显著升高并达到峰值。血清NO,MDA水平及SOD活性均在FS形成中后期发生显著改变。结论测定高脂饮食哺乳动物血浆LPA水平,同时结合血清NO,MDA水平及SOD活性可预警并判定主动脉脂质条纹性病变的严重程度。     

高脂血症,脂质过氧化,抗氧化酶活性与动脉粥样硬化的关系

用大剂量胆固醇(1.5g/日)喂家兔60天后停胆固醇30天塑造动脉粥样硬化(AS)模型。观察血胆固醇、过氧化脂(LPO)含量和抗氧化酶活性与AS病变发生发展的关系。发现:血清胆固醇水平随喂胆固醇时间延长而升高,至60天时达高峰,停饲胆固醇,血清胆固醇水平迅速下降,而同样升高的LPO水平不但未降,反而继续升高,明显高于对照的水平。抗氧化酶SOD和GSH-Px活性在LPO升高的早期显示代偿性增高,以后即降低并保持在低于对照的水平。主动脉、肺动脉和冠状动脉均发生程度不等的AS病变,即使在停饲胆固醇一个月后亦可见进行性病变,如大量平滑肌细胞增生和炎细胞浸润,且其病变较前更重。以上结果提示,血中过量的LPO抑制了抗氧化酶活性,可能在AS的发生发展中起重要作用。     

Effect of vitamin E on periodontitis: Evidence and proposed mechanisms of action

BackgroundPeriodontitis is a noncommunicable inflammatory disease of the soft tissue and bone surrounding the teeth in the jaw, which affects susceptible individuals with poor oral hygiene. A growing interest has been seen in the use of dietary supplements and natural products for the treatment and prevention of periodontitis. Vitamin E consists of two major groups, namely tocopherols and tocotrienols, which are botanical lipophilic compounds with excellent anti-inflammatory and antioxidant properties.HighlightThis review aimed to summarize the preclinical and clinical findings on the effects of vitamin E on periodontitis. The current literature suggests that vitamin E could improve the periodontal status by correcting redox status imbalance, reducing inflammatory responses, and promoting wound healing, thus highlighting the potential of vitamin E in the management of periodontitis.ConclusionDirect evidence for the use of vitamin E supplementation or treatment of periodontitis in humans is still limited. More well-designed and controlled studies are required to ascertain its effectiveness.     

急性脑卒中患者血清一氧化氮、一氧化氮合酶、丙二醛、超氧化期歧化酶及过氧化脂质水平动态变化与病情预后分析

目的通过对216例急性脑卒中患者血清一氧化氮（NO）、一氧化氮合酶（NOS）、丙二醛（MDA）、超氧化物歧化酶（SOD）、过氧化脂质（LPO）水平变化的动态观察,探讨这5项指标与急性脑卒中病情变化及预后之间的关系。方法采用生物化学方法检测急性脑卒中患者血清第1～4周NO、NOS、MDA、SOD、LPO含量水平,并与正常对照组比较。结果①急性脑卒中组NO、NOS、MDA、LPO水平均明显高于正常对照组（P均（0.01）,发病后第1周显著升高,随着病情的好转,第2～4周逐渐下降;SOD水平明显低于正常对照组（P（0.01）,发病后第1周显著降低,第2～4周逐渐升高。②出血性脑卒中NO、NOS、MDA、LPO水平明显高于缺血性脑卒中组（P（0.01）,而SOD水平则明显降低（P（0.05）。结论急性脑卒中患者存在NO、NOS、MDA、SOD、LPO含量失衡的变化,并随病情的严重与演变而变化。观察这5项指标的水平动态变化,可作为判定病情和评价预后的参考指标。