Protective Effect of Plumbago zeylanica Against Cyclophosphamide-Induced Genotoxicity and Oxidative Stress in Swiss Albino Mice

Plumbago zeylanica, commonly known as white leadwort, found abundantly in the plains of Bengal and southern India, was tested for its possible in vivo protective effect against cyclophosphamide-induced genotoxicity and oxidative stress in Swiss albino mice. Pretreatment with the alcoholic root extract of Plumbago zeylanica (250 and 500 mg/kg body weight orally for 5 days) significantly reduced the frequency of micronucleated polychromatic erythrocytes (MnPCEs), increased the PCE/NCE (normochromatic erythrocyte) ratio in the bone marrow, and decreased the levels of lipid peroxidation products with concomitant changes in the status of antioxidants. Both doses of Plumbago zeylanica were effective in exerting a protective effect against cyclophosphamide-induced genotoxicity and oxidative stress.     

Protective effect of Diosmin against benzo(a)pyrene‐induced lung injury in Swiss Albino Mice

Diosmin, a naturally occurring flavonoid commonly present in citrus fruit, is known to exhibit anti‐inflammatory, antimutagenic, antioxidant, and free radical scavenging as well as blood lipid lowering activities among others. Diosmin has also been used for the treatment of various diseases including diabetes mellitus and Alzheimer's disease. Our study explores the role of Diosmin in pulmonary toxicity (lung injury) induced by environmental contaminant benzo(a)pyrene [B(a)P]. Swiss Albino Mice (SAM) were administered with either Diosmin 100 or 200 mg/kg body weight daily for 14 days and then challenged with a single dose of B(a)P. On the 15th day, animals were sacrificed; lung tissues and blood were collected for molecular analysis. B(a)P administration in mice induced the thickening of lung epithelium, damaged alveolar architecture, and promoted inflammatory cell infiltration in the lung tissues. Also, B[a]P significantly increased the expression of NF‐kB, COX‐2, IL‐6, Bax, cleaved caspase 3, and cleaved PARP proteins and decreased antioxidant enzyme levels. Diosmin‐100 and Diosmin‐200 significantly attenuated the damage to lung epithelium, alveolar architecture, and reduced inflammatory cell infiltration in the lung tissues of mice. Diosmin significantly (P < .05) attenuated the levels of oxidative stress markers: lactate dehydrogenase and xanthine oxidase. A decrease in expression of NF‐kB, COX‐2, IL‐6, Bax, cleaved caspase 3, and cleaved PARP proteins in mice was challenged with B[a]P. Diosmin thus could be a promising therapeutic adjuvant against B[a]P‐induced oxidative stress and lung damage.     

Protective effect of saffron extract against doxorubicin cardiotoxicity in isolated rabbit heart

Abstract

Context: Anticancer treatments such as anthracyclines are effective; however, they induce cardiotoxicity by releasing radical oxygen species (ROS). Saffron (Crocus sativus; Iridaceae) is a widely used spice with antioxidant properties and numerous health benefits that may provide cardioprotection.

Objective: To assess the effect of saffron against acute myocardium damage by anthracyclines compared with electrolysis as a free radical generating system.

Materials and methods: According to the Langendorff method, we used the model of an isolated rabbit heart perfused in retrograde. In one set of experiments, ROS was generated by electrolysis of the perfused heart solution (3?mA for 30?min) in the presence and absence of saffron extracts at the optimal dose (10?μg/ml). In another set, we perfused the heart with anthracycline, i.e. 30?μM doxorubicin (Doxo) in the presence and absence of 10?μg/ml saffron extracts. We evaluated cardiodynamics, as well as biochemical and pathological parameters, to emphasize the effectiveness of the treatment with saffron extract using the optimal dose of catalase (150?IU) as a positive control.

Results: ROS generated, respectively, by electrolysis and by Doxo significantly (p?<?0.05) affects cardiovascular function; it decreased ventricular pressure (45.02 and 40.41%), heart rate (36.31 and 22.39%) and coronary flow (50.98 and 36.67%). Increased lipid peroxidation of the myocardium was also observed (118.22 and 56.58%), while superoxide dismutase activity decreased (48.33 and 38.70%). The myocardial architecture was altered and the intercellular spaces increased.

Conclusion: Saffron perfused during electrolysis helps trap ROS and significantly improves myocardial function; however, saffron was less effective against Doxo, thus suggesting that mechanisms other than oxidative stress underlie Doxo cardiotoxicity.     

Inhibition of Benzoyl Peroxide–Induced Cutaneous Oxidative Stress,Toxicity, and Ear Edema in Mice by Nardostachys jatamansi.

Abstract

Recent years have shown considerable efforts to identify new chemopreventive agents that could be of clinical value. In the current study, modulatory effect of Nardostachys jatamansi. (Jones) DC on benzoyl peroxide–induced oxidative stress, toxicity, and ear edema is investigated. Pretreatment with jatamansi at doses of 2.5 and 5 mg/kg body weight in acetone prior to the application of benzoyl peroxide (20 mg/animal per 0.2 ml acetone) resulted in significant inhibition of benzoyl peroxide–induced cutaneous oxidative stress, toxicity, and ear edema in a dose-dependent manner. The cutaneous microsomal membrane lipid peroxidation and xanthine oxidase activities were significantly reduced (p < 0.05). Moreover, the depleted levels of phase II metabolizing enzymes and glutathione were recovered significantly (p < 0.05). Our findings suggest that N. jatamansi. is an effective chemopreventive agent in mouse skin with potential of ameliorating benzoyl peroxide–induced cutaneous oxidative stress, toxicity, and ear edema.     

替米沙坦对血管紧张素Ⅱ诱导的血管内皮细胞氧化/还原失衡的保护作用

目的：探讨AngⅡ对血管内皮细胞氧化/还原平衡的影响及替米沙坦的保护作用。方法：人大动脉血管内皮细胞株接种于35mm玻璃底细胞培养皿中,随机分成空白对照组、血管紧张素Ⅱ模型组及三个浓度替米沙坦试验组（60μg/L、300μg/L、1000μg/L）5组,每组42例样本。测定不同取样时间点血管内皮细胞SOD活性和MDA含量。结果：血管内皮细胞受AngⅡ刺激后,细胞MDA含量瞬时激增,SOD活性受到抑制,替米沙坦预处理过的血管内皮细胞能有效抵御AngⅡ诱发的氧化应激反应,提高SOD活性和抑制MDA含量的升高,并呈现替米沙坦剂量依赖性关系。结论：替米沙坦抑制AngⅡ诱导的细胞氧化应激反应,从多方面保护动脉血管。     

Antitumor Activity of the Methanol Extract of Hypericum hookerianum Stem Against Ehrlich Ascites Carcinoma in Swiss Albino Mice

A large number of plants belonging to the Hypericum family are known to possess strong antitumor properties. The methanol extract of H. hookerianum Wight and Arnott stem (MEHH) exhibited potent in vitro cytotoxic activity against various cancerous cell lines. In the present study, the high performance liquid chromatography (HPLC) standardized MEHH was tested for in vivo antitumor properties against Ehrlich ascites carcinoma (EAC) tumor bearing mice at 100, 200, and 400 mg/kg body weight doses given orally once daily for 14 days. The results indicate that administration of the extract not only increased the survival of animals with ascites tumor, decreased the body weight induced by the tumor burden, and reduced packed cell volume and viable tissue cell count, but also altered many hematological parameters changed during tumor progression, indicating the potent antitumor nature of the extract. Among the three doses tested, the 200 mg/kg body weight dose was found to be the most potent.     

黄杞苷保护DNA氧化损伤的活性及其可能机制

目的 研究黄杞苷保护DNA氧化损伤的活性与可能机制。方法 采用DNA保护分析法、超氧自由基（·O₂^-）清除法、Ferrozine显色法,探讨其保护DNA氧化损伤的活性与可能机制,并通过紫外可见光谱（UV-vis spectra）考察其与Fe²⁺络合的变化。结果 在DNA保护分析法、·O₂^-自由基清除法、Ferrozine显色法中,黄杞苷在一定浓度范围内,表现出浓度依赖性。其IC₅₀值分别（60.3±9.9）,（44.5±7.6）,（159.7±19.9）μg·mL^-1。UV-vis光谱分析表明,黄杞苷与Fe²⁺混合后,在波长475 nm处出现新的峰,摩尔消光系数为102.5 L·mol^-1·cm^-1。结论 黄杞苷能较好地保护DNA,免受羟基自由基（·OH）诱导的氧化损伤。其保护作用由直接清除ROS和间接清除ROS 2个途径实现。黄杞苷直接清除ROS,可能与氢转移和电子转移有关;间接清除ROS可能通过络合Fe²⁺的方式,阻断·OH自由基生成。不过,受3-位鼠李糖基的空间位阻影响,其Fe²⁺络合能力较弱。     

Studies on the Cytotoxic, Biochemical and Anti-Carcinogenic Potentials of Ninhydrin on Ehrlich Ascites Carcinoma Cell-Bearing Swiss Albino Mice

Ninhydrin (2,2-dihydroxy-1, 3-indane dione)was evaluated for its antitumor and cytotoxicproperties in Ehrlich ascites carcinoma cell (EACCell)-bearing mice. The rationale behind this studyhas been mainly the literature reports of itscharacteristic interference with DNA synthesis andcalcium homeostasis. Antitumor activity was evaluatedfrom the total count and viability of EAC cells inaddition to their nucleic acid, protein, non-proteinsulfhydryls (NP-SH) and malondialdehyde (MDA)contents. The EAC cell-bearing animals were alsoobserved for the effect on their survival and bodyweight variations. In addition, the tumors grown atthe site of injection were evaluated forhistopathological changes. Ninhydrin treatments (5, 10and 20 mg/kg/day) abate the increase in body weightand advanced the duration of survival in EACcell-bearing mice. The results on histopathologicalinvestigations show retardation in tumor growth,decreased frequency of mitotic figures and hairfollicles and an increased necrosis in the tumor byninhydrin treatment. Our results on cytotoxicity,which demonstrated compression in the number of EACcells and their viability substantiate these data. Theresults of biochemical studies on EAC cells exhibit areduction in the levels of DNA, RNA, proteins andNP-SH with a subsequent increase in the concentrationsof MDA after ninhydrin treatment. Inhibition in tumorgrowth was dose dependently significant with the samedose regimen. The observed cytotoxic and antitumoractivity of ninhydrin was comparable tocyclophosphamide. The possible mode of action ofninhydrin-induced cytotoxic and antitumor activityappear to be due to its interference withmitochondrial function resulting in inhibition of DNAsynthesis, an effect that is being investigatedfurther.     

糖尿病大鼠肾脏抗氧化防御系统机能的改变

目的：探讨糖尿病对肾脏抗氧化防御机能的影响。方法：观察12周糖尿病大鼠肾皮质丙二醛(MDA)及谷胱甘肽(GSH)水平,以及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、谷胱甘肽S转移酶(GSH-ST)和过氧化氢酶(CAT)活性的变化。结果：糖尿病大鼠肾组织中SOD、CAT活性下降;GSH含量显著降低;MDA没有变化;GSH-PX活性却明显增强。结论：糖尿病大鼠肾组织抗氧化防御机能明显下降。     

The discovery and development of new potential antioxidant agents for the treatment of neurodegenerative diseases

Introduction: Several neurodegenerative disorders (NDs) including Alzheimer’s and Huntington’s diseases have had associations with the oxidative process and free radical damage. Consequently, in past decades, several natural and synthetic antioxidants have been assessed as therapeutic agents but have shown limitations in bioavailability, metabolic susceptibility and permeability to the blood brain barrier. Given these issues, medicinal chemists are hard at work to modify/improve the chemical structures of these antioxidants, thereby improving their efficacy.

Areas covered: In this review, the authors critically analyze several biological mechanisms involved in the generation of free radicals. Additionally, they analyze free radicals’ role in the generation of oxidative stress and in the progression of many NDs. Further, the authors review a collection of natural and synthetic antioxidants, their role as free radical scavengers along with their mechanisms of action and their potential for preventing neurodegenerative diseases.

Expert opinion: So far, preclinical studies on several antioxidants have shown promise for treating NDs, despite their limitations. The authors do highlight the lack of the adequate animal models for preclinical assessment and this does hinder further progression into clinical trials. Further studies are necessary to fully investigate the potential of these antioxidants as ND therapeutic options.     

Free radicals and related reactive species as mediators of tissue injury and disease: implications for Health

Abstract

A radical is any molecule that contains one or more unpaired electrons. Radicals are normal products of many metabolic pathways. Some exist in a controlled (caged) form as they perform essential functions. Others exist in a free form and interact with various tissue components. Such interactions can cause both acute and chronic dysfunction, but can also provide essential control of redox regulated signaling pathways. The potential roles of endogenous or xenobiotic-derived free radicals in several human pathologies have stimulated extensive research linking the toxicity of numerous xenobiotics and disease processes to a free radical mechanism. In recent years, improvements in analytical methodologies, as well as the realization that subtle effects induced by free radicals and oxidants are important in modulating cellular signaling, have greatly improved our understanding of the roles of these reactive species in toxic mechanisms and disease processes. However, because free radical-mediated changes are pervasive, and a consequence as well as a cause of injury, whether such species are a major cause of tissue injury and human disease remains unclear. This concern is supported by the fact that the bulk of antioxidant defenses are enzymatic and the findings of numerous studies showing that exogenously administered small molecule antioxidants are unable to affect the course of most toxicities and diseases purported to have a free radical mechanism. This review discusses cellular sources of various radical species and their reactions with vital cellular constituents, and provides examples of selected disease processes that may have a free radical component.     

Evaluation of Antioxidant Potential of Terminalia chebula. Fruits Studied in Streptozotocin-Induced Diabetic Rats

Abstract

Oxidative stress is believed to be a pathogenic factor in the development of diabetic complications. Recently, we have reported the antidiabetic activity of Terminalia chebula. Retz. (Combretaceae) fruits on streptozotocin (STZ)-induced experimental diabetes. The current study was aimed to evaluate the antioxidant potential of Terminalia chebula. fruits on STZ-induced diabetic rats. Oral administration of ethanol extract of Terminalia chebula. fruit at a concentration of 200 mg/kg body weight for 30 days significantly controlled the alteration in the levels of thiobarbituric acid reactive substances, hydroperoxides, and both enzymatic and nonenzymatic antioxidants. In addition, the treatment also resulted in a significant decrease in the levels of blood glucose and glycosylated hemoglobin. The results are comparable with glibenclamide, a known hypoglycemic drug. The presence of biologically active ingredients in the fruit extract may be responsible for the antioxidant properties of the Terminalia chebula. fruits, which in turn may be partially responsible for its antidiabetogenic properties.     

口服鲨鱼肝再生因子脂质体对小鼠急性肝损伤的保护作用

为研究口服鲨鱼肝再生因子脂质体对四氯化碳(CCl4)和硫代乙酰胺(TAA)对小鼠急性肝损伤的保护作用,采用CCl4和TAA致小鼠肝损伤,观察肝组织切片,测定生化指标,检测小鼠给药后血清谷丙转氨酶(ALT)、血清谷草转氨酶(AST)活力。结果口服鲨鱼肝再生因子脂质体能明显减轻CCl4和TAA所致小鼠急性肝损伤模型的肝组织损伤作用,降低ALT、AST活力。因此口服鲨鱼肝再生因子脂质体对急性肝损伤也有明显的保护作用。     

Effect of dietary antioxidant on mercuric chloride induced lung toxicity and oxidative stress

This study was conducted to evaluate the effect of environmental contaminant mercuric chloride on levels of trace elements and oxidative parameters in rat lungs and to investigate the efficacy of possible protection by natural antioxidant diallylsulphide (DAS) against lung injury. Twenty-four healthy male rats were randomly divided into four groups: I – control, II – DAS (200?mg/kg), III – HgCl₂ (50?mg/kg), and IV – DAS (200?mg/kg) + HgCl₂ (50?mg/kg). Mercuric chloride induced oxidative stress was indicated by a significant decrease in levels of superoxide dismutase, catalase, and glutathione peroxidase as compared to the control group (p–<0.05). Also, hydroxyproline (HYP) content in lung tissues of mercuric chloride-treated group was significantly increased (p?<?0.05). DAS markedly attenuated mercuric-induced biochemical alterations in lungs by upregulating the activities of antioxidant enzymes. These findings indicated that within the doses selected, DAS can provide significant protection against HgCl₂-induced toxicity.     

葡萄籽原花青素对酒精性肝损伤小鼠的保护作用

目的 考察葡萄籽原花青素（grape seed procyanidin,GSP）对酒精性肝损伤小鼠的保护作用及其抗炎机制。方法 ICR小鼠60只,♂,随机分成正常对照组、模型组（56%乙醇）、水飞蓟素组（56%乙醇+90 mg·kg^-1·d^-1水飞蓟素）及GSP高、中、低剂量组（56%乙醇+400,200,100 mg·kg^-1·d^-1GSP）。8周后用分光光度法检测血清中ALT、AST水平,肝MDA含量和SOD、GSH-Px活力;酶联免疫法检测肝NF-κB、TNF-α、IL-1β的含量;HE染色检测肝脏病理改变。结果 与模型组比较,GSP可以降低酒精性肝损伤小鼠血清中ALT、AST含量及肝组织中MDA、NF-κB、TNF-α、IL-1β含量（P<0.05）,提高SOD、GSH-PX活力（P<0.05）,减轻肝脏的病理损伤程度（P<0.05）。结论 GSP对酒精性肝损伤小鼠具有保护作用,其机制可能是通过抗氧化和降炎症反应来发挥作用。     

Hydroxyl scavenging activity accounts for differential antioxidant protection of Plantago major against oxidative toxicity in isolated rat liver mitochondria

Objectives The aim of this work was to study the effects of P. major against the oxidative damage of isolated rat liver mitochondria. Methods The extracts were obtained using methanol (MeOH), ethyl acetate (EAc), dichloromethane (DCM), and hexane (Hex) as solvents. Key findings Hex, DCM, and EAc totally, and MeOH partially, inhibited ROS generation and lipid peroxidation of membranes induced by Fe²⁺ or t‐BOOH. However, only MeOH was able to prevent the t‐BOOH‐induced glutathione and NAD(P)H oxidation. All extracts chelated Fe²⁺ and reduced DPP Hradicals. EPR analysis revealed that P. major exhibited potent scavenger activity for hydroxyl radicals. Conclusions The potent antioxidant activity exhibited by P. major was able to prevent oxidative mitochondrial damage, contributing to the understanding of its hepatoprotective action against ROS‐mediated toxicity.     

四逆散对应激性肝郁小鼠的保护作用机制研究

目的利用小鼠拘束应激负荷模型评价四逆散汤剂的疏肝解郁作用,并通过检测应激性激素水平以及和肝脏炎症、氧化水平的变化探讨其可能的作用机制。方法建立小鼠拘束应激肝郁模型,测定血浆丙氨酸氨基转移酶（ALT）、天门冬酸氨基转移酶（AST）、皮质酮（CORT）水平,检测肝组织激素受体（GR）基因表达水平、抗氧化能力指数（ORAC）、丙二醛（MDA）水平、一氧化氮（NO）水平、超氧化物歧化酶（SOD）及谷胱甘肽过氧化物酶（GSH—Px）的活性。结果与模型组相比,四逆散能显著降低应激小鼠血浆ALT和AST水平,并能降低拘束负荷小鼠血浆CORT水平和肝组织NO及MDA水平,提高ORAC水平、SOD及GSH—Px活性。结论四逆散的疏肝解郁作用可能与缓解应激负荷引起的肝损伤有关,其保护机制与抑制应激负荷引起的炎症发生以及氧化损伤作用有关。     

N-乙酰半胱氨酸和维生素C抗大鼠急性肺损伤作用的比较研究

目的比较研究N-乙酰半胱氨酸（NAC）和维生素C（Vc）抗大鼠急性肺损伤（ALI）作用。方法采用大鼠油酸（OA）所致急性肺损伤模型,随机分为正常对照组（NS组）、AU模型组（OA组）、维生素C干预组（Vc组）、NAC干预组（NAC组）。观察NAC和vc对大鼠急性肺损伤时MDA,SOD和GSH—PX水平,病理改变,肺系数,免疫组化iNOS等的影响。结果NAC组和Vc组可明显降低损伤所致肺系数、iNOS表达、组织MDA等水平的升高;同时,又能显著升高肺组织SOD、GSH—PX水平,且Vc组和NAC组之间无显著性差别（P〉0．05）。结论抗氧化剂NAC和Vc可通过抑制MDA、iNOS表达,改善SOD、GSH—Px等方式减少氧自由基的产生,减轻肺损伤程度,对油酸所致急性肺损伤后的肺纤维化有一定防护作用。     

In Vivo Micronucleus Assay and GST Activity in Assessing Genotoxicity of Plumbagin in Swiss Albino Mice

Information available on the mutagenicity of a large number of indigenous drugs commonly employed in the Siddha and Ayurveda systems of medicine is scanty. In this context, the current investigation on plumbagin, 5-hydroxy-2methyl-1,4-napthoquinone, an active principle in the roots of Plumbago zeylanica used in Siddha and Ayurveda for various ailments, was carried out; 16 mg/kg b.w. (LD₅₀) was fixed as the maximum dose. Subsequent dose levels were fixed as 50% and 25% of LD₅₀ amounting to 8 mg and 4 mg/kg b.w., respectively, and given orally for 5 consecutive days in 1% Carboxyl Methyl Cellulose (CMC) to Swiss albino mice weighing 25–30 g. The micronucleus assay was done in mouse bone marrow. Plumbagin was found to induce micronuclei at all the doses studied (4 mg/kg, 8 mg/kg, 16 mg/kg b.w.), and it proves to be toxic to bone marrow cells of Swiss albino mice. Animal treated with cyclophosphamide (40 mg/kg b.w.) served as positive control. In addition, glutathione S-transferase (GST) activity was observed in control, plumbagin (4 mg, 8 mg, 16 mg/kg b.w., respectively), and genotoxin-treated experimental group of animals. No significant change in GST activity was observed with plumbagin dose of 4 mg/kg b.w., whereas GST activity was significantly inhibited by higher doses of plumbagin (8 mg and 16 mg/kg b.w.) and cyclophosphamide.