Juglone from Walnut Produces Cardioprotective Effects against Isoproterenol-Induced Myocardial Injury in SD Rats

Therapeutic and/or preventive interventions using phytochemical constituents for ischemic heart disease have gained considerable attention worldwide, mainly due to their antioxidant activity. This study investigated the cardioprotective effect and possible mechanism of juglone, a major constituent of the walnut tree, using an isoproterenol (ISO)-induced myocardial infarction (MI) model in rats. Rats were pretreated for five (5) days with juglone (1, 3 mg/kg, i.p) and atenolol (1 mg/kg, i.p) in separate experiments before inducing myocardial injury by administration of ISO (80 mg/kg, s.c) at an interval of 24 h for 2 consecutive days (4th and 5th day). The cardioprotective effect of juglone was confirmed through a lead II electrocardiograph (ECG), cardiac biomarkers (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological study. The results of our present study suggest that prior administration of juglone (1 and 3 mg/kg) proved to be effective as a cardioprotective therapeutic agent in reducing the extent of myocardial damage (induced by ISO) by fortifying the myocardial cell membrane, preventing elevated T-waves, deep Q-waves in the ECG, heart to body weight ratio, infarction and also by normalizing cardiac marker enzymes (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological changes, such as inflammation, edema and necrosis. In conclusion, this study has identified phytochemical constituents, in particular juglone, as a potential cardioprotective agent.     

Cardioprotective Effect of Paeonol and Danshensu Combination on Isoproterenol-Induced Myocardial Injury in Rats

Background

Traditional Chinese medicinal herbs Cortex Moutan and Radix Salviae Milthiorrhizaeare are prescribed together for their putative cardioprotective effects in clinical practice. However, the rationale of the combined use remains unclear. The present study was designed to investigate the cardioprotective effects of paeonol and danshensu (representative active ingredient of Cortex Moutan and Radix Salviae Milthiorrhizae, respectively) on isoproterenol-induced myocardial infarction in rats and its underlying mechanisms.

Methodology

Paeonol (80 mg kg⁻¹) and danshensu (160 mg kg⁻¹) were administered orally to Sprague Dawley rats in individual or in combination for 21 days. At the end of this period, rats were administered isoproterenol (85 mg kg⁻¹) subcutaneously to induce myocardial injury. After induction, rats were anaesthetized with pentobarbital sodium (35 mg kg⁻¹) to record electrocardiogram, then sacrificed and biochemical assays of the heart tissues were performed.

Principal Findings

Induction of rats with isoproterenol resulted in a marked (P<0.001) elevation in ST-segment, infarct size, level of serum marker enzymes (CK-MB, LDH, AST and ALT), cTnI, TBARS, protein expression of Bax and Caspase-3 and a significant decrease in the activities of endogenous antioxidants (SOD, CAT, GPx, GR, and GST) and protein expression of Bcl-2. Pretreatment with paeonol and danshensu combination showed a significant (P<0.001) decrease in ST-segment elevation, infarct size, cTnI, TBARS, protein expression of Bax and Caspase-3 and a significant increase in the activities of endogenous antioxidants and protein expression of Bcl-2 and Nrf2 when compared with individual treated groups.

Conclusions/Significance

This study demonstrates the cardioprotective effect of paeonol and danshensu combination on isoproterenol-induced myocardial infarction in rats. The mechanism might be associated with the enhancement of antioxidant defense system through activating of Nrf2 signaling and anti-apoptosis through regulating Bax, Bcl-2 and Caspase-3. It could provide experimental evidence to support the rationality of combinatorial use of traditional Chinese medicine in clinical practice.     

Protective Effect of Cornuside against Carbon Tetrachloride-Induced Acute Hepatic Injury

This study elucidated the effects of cornuside on carbon tetrachloride (CCl₄)-induced hepatotoxicity. Rats were treated intraperitoneally with 0.5 mL/kg of CCl₄. Sixteen h after CCl₄ treatment, the levels of serum aminotransferases, tumor necrosis factor-α (TNF-α), and lipid peroxidation were significantly elevated, whereas the hepatic antioxidative enzyme activities were decreased. These changes were attenuated by cornuside. Histological studies also indicated that cornuside inhibited CCl₄-induced liver damage. Furthermore, the contents of hepatic nitrite, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were elevated after CCl₄ treatment, while cytochrome P450 2E1 (CYP2E1) expression was suppressed. Cornuside treatment inhibited the formation of liver nitrite, and reduced the overexpression of iNOS and COX-2 proteins, but restored the liver CYP2E1 content as compared with the CCl₄-treated rats. Our data indicate that cornuside protects the liver from CCl₄-induced acute hepatotoxicity, perhaps due to its ability to restore the CYP2E1 function and suppress inflammatory responses, in combination with its capacity to reduce oxidative stress.     

Caspase-12抑制剂对百草枯中毒大鼠肝损伤的保护作用

目的:观察caspase-12抑制剂Z-ATAD-FMK对百草枯染毒大鼠肝脏caspase-12蛋白表达和肝细胞凋亡的影响,以及通过血清SOD和MDA的检测,探讨其对百草枯中毒大鼠肝脏保护作用和对机体氧化应激反应的作用。方法:50只健康Wistar大鼠随机分三组:A组为正常对照组;B组为模型组(PQ染毒);C组抑制剂组(PQ/Z-ATAD-FMK),于3d、7d处死B组和C组各10只大鼠。取血检测ALT、TBIL、SOD和MDA;HE染色观察肝组织病理学变化;免疫组化法检测caspase-12蛋白;二苯胺法检测细胞凋亡率。SPSS18.0统计分析。结果:Z-ATAD-FMK抑制剂组ALT、TBIL、MDA值低于模型组(P0.05),SOD高于模型组(P0.05);caspase-12蛋白表达和细胞凋亡率亦低于模型组(P0.05);HE染色显示凋亡和坏死程度也较模型组轻。结论:Caspase-12抑制剂Z-ATAD-FMK能减少百草枯中毒大鼠肝脏caspase-12蛋白表达和肝细胞凋亡率,减轻肝细胞坏死,对肝脏具有保护作用,同时可以抑制百草枯中毒大鼠的氧化应激反应。     

Carnosine Protects the Brain of Rats and Mongolian Gerbils against Ischemic Injury: After-Stroke-Effect

Carnosine, a specific constituent of excitable tissues of vertebrates, exhibits a significant antioxidant protecting effect on the brain damaged by ischemic-reperfusion injury when it was administered to the animals before ischemic episode. In this study, the therapeutic effect of carnosine was estimated on animals when this drug was administered intraperitoneally (100 mg/kg body weight) after ischemic episode induced by experimental global brain ischemia. Treatment of the animals with carnosine after ischemic episode under long-term (7–14 days) reperfusion demonstrated its pronounced protective effect on neurological symptoms and animal mortality. Carnosine also prevented higher lipid peroxidation of brain membrane structures and increased a resistance of neuronal membranes to the in vitro induced oxidation. Measurements of malonyl dialdehyde (MDA) in brain homogenates showed its increase in the after brain stroke animals and decreased MDA level in the after brain stroke animals treated with carnosine. We concluded that carnosine compensates deficit in antioxidant defense system of brain damaged by ischemic injury. The data presented demonstrate that carnosine is effective in protecting the brain in the post-ischemic period. Special issue dedicated to Dr. Bernd Hamprecht     

A Possible Novel Protective Effect of Piceatannol against Isoproterenol (ISO)-Induced Histopathological,Histochemical, and Immunohistochemical Changes in Male Wistar Rats

Dry mouth is characterized by lower saliva production and changes in saliva composition. In patients with some salivary gland function remaining, pharmaceutical treatments are not recommended; therefore, new, more effective methods of promoting saliva production are needed. Hence, this study aimed to provide an overview of the histological changes in the salivary gland in the model of isoproterenol (ISO)-induced degenerative changes in male Wistar rats and to evaluate the protective effect of piceatannol. Thirty-two male Wistar rats were randomly divided into four groups: the control group, the ISO group, and the piceatannol (PIC)-1, and -2 groups. After the third day of the experiment, Iso (0.8 mg/100 g) was injected intraperitoneally (IP) twice daily into the animals. PIC was given IP in different daily doses (20 and 40 mg/kg) for three days before ISO and seven days with ISO injection. The salivary glands were rapidly dissected and processed for histological, histochemical, immunohistochemical (Ki-67), and morphometric analysis. Upon seven days of treatment with ISO, marked hypertrophy was observed, along with an increased number of positive Ki-67 cells. Proliferation was increased in some endothelial cells as well as in ducts themselves. Despite the significant decrease in proliferation activity, the control group did not return to the usual activity level after treatment with low-dose PIC. Treatment with a high dose of PIC reduced proliferative activity to the point where it was substantially identical to the results seen in the control group. An ISO-driven xerostomia model showed a novel protective effect of piceatannol. A new era of regenerative medicine is dawning around PIC’s promising role.     

吸氧预处理对大鼠脑缺血再灌注损伤的保护作用

目的探讨吸氧预处理对大鼠脑缺血再灌注损伤的保护作用。方法通过大鼠局灶脑缺血再灌注损伤模型,采用SOD、MDA测定、电镜及神经行为学检查的方法,观察吸氧预处理对大鼠脑缺血再灌注损伤后SOD、MDA、神经行为学评分及脑组织病理变化。结果吸氧预处理组SOD活力高于对照组(P<0.05),MDA含量、神经行为学评分均低于对照组(P<0.05),脑组织超微结构损伤均减轻。结论吸氧预处理对大鼠脑缺血再灌注损伤有保护作用。     

Protective Effect of Grape Seed Polyphenols against High Glucose-Induced Oxidative Stress

We aimed to clarify whether grape seed polyphenols (GSPs) are candidates therapeutic agents against diabetes mellitus, and to determine what degree of GSP oligomerization has the most potent efficacy. We studied the protective effects of various molecular weight GSPs (monomer, oligomer, polymer, and oligonol) on high glucose-induced cytotoxicity. In the present study, a high concentration of glucose (30 mM) induced cytotoxicity and oxidative stress (reactive oxygen species and nitric oxide) in cultured LLC-PK₁ cells, but treatment with GSPs, especially oligomer GSPs, had potent protective effects against high glucose-induced oxidative stress. In addition, high glucose induced nuclear translocation of nuclear factor-kappa B, and increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and bax, but GSP treatment inhibited them. These results indicate that GSPs have protective effects against high glucose-induced cytotoxicity, and among them, oligomer GSPs have more potent effects than other GSPs (monomer, polymer, and oligonol) on high glucose-induced renal cell damage.     

梓醇对大鼠脑缺血再灌注损伤的保护作用研究

目的:探讨梓醇对缺血再灌注大鼠脑损伤后的保护作用.方法:采用传统大脑中动脉阻塞(MCAO)方法制备大鼠局灶性缺血模型,根据随机数字表法将SD大鼠分为MCAO组、对照组(vehicle组)及梓醇处理组(catalpol组),缺血再灌注48 h后观察各组大鼠神经功能学评分和脑梗死容积.分别于术前、术后6h、24 h、48 h取大鼠脑组织样本,检测匀浆中谷胱甘肽过氧化物酶(GSH-PX)和丙二醛(MDA)的变化情况.结果:与vehicle组和MCAO组相比,catalpol处理组神经功能学评分降低(P＜0.05);其梗死容积较小(P＜0.05).组织匀浆结果显示catalpol处理组脑匀浆中GSH-PX活力升高,MDA含量下降(P＜0.05).结论:梓醇可能通过降低脑内自由基水平、控制脂质过氧化程度,对缺血再灌注引起的大鼠脑损伤产生神经保护作用.     

Protective Effect of Metalloporphyrins against Cisplatin-Induced Kidney Injury in Mice

Oxidative and nitrative stress is a well-known phenomenon in cisplatin-induced nephrotoxicity. The purpose of this work is to study the role of two metalloporphyrins (FeTMPyP and MnTBAP), water soluble complexes, in cisplatin-induced renal damage and their ability to scavenge peroxynitrite. In cisplatin-induced nephropathy study in mice, renal nitrative stress was evident by the increase in protein nitration. Cisplatin-induced nephrotoxicity was also evident by the histological damage from the loss of the proximal tubular brush border, blebbing of apical membranes, tubular epithelial cell detachment from the basement membrane, or intra-luminal aggregation of cells and proteins and by the increase in blood urea nitrogen and serum creatinine. Cisplatin-induced apoptosis and cell death as shown by Caspase 3 assessments, TUNEL staining and DNA fragmentation Cisplatin-induced nitrative stress, apoptosis and nephrotoxicity were attenuated by both metalloporphyrins. Heme oxygenase (HO-1) also plays a critical role in metalloporphyrin-mediated protection of cisplatin-induced nephrotoxicity. It is evident that nitrative stress plays a critical role in cisplatin-induced nephrotoxicity in mice. Our data suggest that peroxynitrite is involved, at least in part, in cisplatin-induced nephrotoxicity and protein nitration and cisplatin-induced nephrotoxicity can be prevented with the use of metalloporphyrins.     

葛根素对大鼠肝脏缺血再灌注损伤的保护作用

目的:观察葛根素预处理时大鼠肝脏缺血再灌注损伤的保护作用.方法:雄性SD大鼠,建立肝脏缺血再灌注模型(HIR).随机分为假手术组、HIR组和HIR-葛根素预处理组.分析各组动物血清中谷草转氨酶(AST)、谷丙转氨酶(ALT)及乳酸脱氢酶(LDH)含量的变化,观察肝组织病理学的改变.结果:肝脏缺血再灌注损伤后,与假手术组比较,血清中AST、ALT、LDH含量均显著增加,同时肝脏门静脉周围瘀血明显,可见少量散在的肝细胞片状坏死灶,有少量炎性细胞和单核细胞浸润,肝细胞肿胀、脂肪空泡变性、核浓缩;经40mg/kg剂量的葛根素预处理7天后,与模型组相比,血清中AST、ALT、LDH均显著降低,肝脏的瘀血明显较模型组轻,肝小叶结构基本正常,微血管未见明显损伤,窦间隙稍宽,细胞变性坏死不明显,偶见少量肝细胞坏死.结论:葛根素预处理对大鼠缺血再灌注肝脏损伤有一定的保护作用.     

Protective effect of proanthocyanidins against doxorubicin‐induced nephrotoxicity in rats

Doxorubicin (DOX) exerts toxic effects in several organs particularly kidney. The present study aimed to assess the protective effect of proanthocyanidins (PAs) against DOX‐induced nephrotoxicity in rats. A single dose of DOX (7.5 mg/kg, i.v.) significantly increased kidney weight, kidney/body weight ratio, serum urea, creatinine, tumor necrosis factor alpha levels, and kidney contents of malondialdehyde, nitric oxide, cyclooxygenase‐2, and caspase‐3 activity with significant reduction in final body weight, serum albumin, kidney contents of reduced glutathione (GSH), and superoxide dismutase activity as compared with control group. In contrast, pretreatment with PAs (200 mg/kg, p.o.) for 14 days before DOX and for 7 days after DOX ameliorated kidney function and oxidative stress parameters. Histopathological evidence confirmed the protective effects of PAs from the tissue damage induced by DOX. In conclusion, PAs have a multi‐nephroprotective effect that might be attributed to its antioxidant, anti‐inflammatory, and antiapoptoic activities.     

Protective effect of resveratrol against pembrolizumab-induced hepatotoxicity and neurotoxicity in male rats

The present study investigates the effects of resveratrol (RSV) on brain and liver tissues in rats with pembrolizumab (PEMB)-induced toxicity. Obtained for the study were 28 male Sprague-Dawley rats (3–4 months old) which were divided into four groups: Group 1: Control. Group 2: Administered PEMB at 5 mg/kg/day i.p. for a week. Group 3: Administered RSV orally at the dose of 20 mg/kg/day for 30 days by gavage. Group 4: Administered PEMB and RSV at 20 and 5 mg/kg/day RSV, respectively, for 30 days. The results of this study revealed that PEMB leads to a significant increase in thiobarbituric acid reactive substance (TBARS) levels and a significant decrease in glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) activities, and glutathione (GSH) levels in the liver and brain tissues. The decreased SOD, CAT, GPx activities, and GSH levels increased significantly following RSV treatment in Group 4. The PEMB treatment showed histopathological alterations associated with strong positive cysteinyl aspartic acid-protease-3 (caspase-3) immunoreactivity, while RSV treatment reduced both the expression of caspase-3 protein and the histopathological changes. RSV administration prevents the biochemical, immunological, and histological alterations induced by PEMB. It can be suggested that the lower caspase-3 immunoreactivity in the PEMB + RSV group than in the PEMB group led to an inhibition of RSV on apoptosis.     

Protective effect of salicylates against hydrogen peroxide stress in yeast

Aims:  To investigate the effects of salicylates in Saccharomyces cerevisiae exposed to oxidative stress induced by hydrogen peroxide (H₂O₂).
Methods and Results:  Saccharomyces cerevisiae was cultured through to the postlogarithmic phase of growth. Stress was induced by the addition of 1·5 mmol l⁻¹ H₂O₂ for 1 h, while N-acetyl-l-cysteine (NAC) and glutathione (GSSG) were used as control agents that affect the redox balance. Sodium salicylate, at 0·01–10 mmol l⁻¹or acetylsalicylic acid, at 0·02–2·5 mmol l⁻¹ was administered at various times before hydrogen peroxide stress. Both agents conferred resistance to a subsequent hydrogen peroxide stress, similarly to the induction of the adaptive response observed upon pretreatment with NAC and GSSG. Sodium salicylate was more potent as a short-term, but not as a long-term pretreatment agent, compared to acetylsalicylic acid.
Conclusions:  Pharmacological pretreatment with salicylates resulted in dose related increases in cell survival, indicating the induction of the protective response in yeast.
Significance and Impact of the study:  The possible role of salicylates in the modulation of the hydrogen peroxide stress response in eukaryotic cells address questions on the effects of these commonly used therapeutic agents in a number of disorders exhibiting an oxidative stress component.     

低聚原花青素对过度训练大鼠骨骼肌损伤的保护作用机制

为研究低聚原花青素对过度训练大鼠骨骼肌损伤的保护作用机制,将大鼠随机分为安静对照组(C)、过度训练组(OM)、低聚原花青素干预组(OOM).C组无运动干预,其他组采用42 d递增负荷跑台训练.训练期间,OOM组每天灌胃低聚原花青素1次(150 mg/kg,5 mL/kg),其他组给予等体积蒸馏水.末次训练后即刻取材,经...     

Protective Effects of Garlic and Silymarin on NDEA-Induced Rats Hepatotoxicity

Background ­— The present study was conducted to investigate the chemopreventive effects of garlic extract and silymarin on N-nitrosodiethylamine (NDEA) and carbon tetrachloride (CCl₄)-induced hepatotoxicity in male albino rats. Methods and Results — Animals were pretreated with garlic, silymarin or both for one week prior to the injection of NDEA. Then animals received a single injection of NDEA followed by weekly subcutaneous injections of CCl₄ for 6 weeks. Oral administration was then continued along with the injection of CCl₄ for the duration of the experiment. Serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), hepatic lipid peroxidation (LPO), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione-S-transferase (GST) and glutathione reductase (GSR) were measured. Injection of NDEA induced a significant elevation in serum AST, ALT and ALP. In the liver, NDEA increased oxidative stress through the increase in LPO and decrease in SOD, and GSH-dependent enzymes. Although administration of garlic or silymarin significantly reduced the liver toxicity, combined administration was more effective in preventing the development of hepatotoxicity. Conclusion — These novel findings suggest that silymarin and garlic have a synergistic effect, and could be used as hepatoprotective agents against hepatotoxicity.     

Protective Effect of Resveratrol against Kainate-induced Temporal Lobe Epilepsy in Rats

Resveratrol (Res) is a phytoalexin produced naturally by several plants, which has multi functional effects such as neuroprotection, anti-inflammatory, and anti-cancer. The present study was to evaluate a possible anti-epileptic effect of Res against kainate-induced temporal lobe epilepsy (TLE) in rat. We performed behavior monitoring, intracranial electroencepholography (IEEG) recording, histological analysis, and Western blotting to evaluate the anti-epilepsy effect of Res in kainate-induced epileptic rats. Res decreased the frequency of spontaneous seizures and inhibited the epileptiform discharges. Moreover, Res could protect neurons against kainate-induced neuronal cell death in CA1 and CA3a regions and depressed mossy fiber sprouting, which are general histological characteristics both in TLE patients and animal models. Western blot revealed that the expression level of kainate receptors (KARs) in hippocampus was reduced in Res-administrated rats compared to that in epileptic ones. These results suggest that Res is a potent anti-epilepsy agent, which protects against epileptogenesis and progression of the kainate-induced TLE animal. The authors Z. Wu and Q. Xu contributed equally to this work.     

不同剂量瘦素预处理对糖尿病大鼠心肌缺血再灌注损伤的保护作用

目的:探讨不同剂量瘦素预处理对糖尿病大鼠心肌缺血再灌注损伤的保护作用。方法:将72只大鼠随机分为对照组、假手术组、心肌梗死组以及大、中、小剂量瘦素预处理组。对照组给予普通饲料喂养,其余各组均给予高糖高脂喂养。1个月后,采大鼠静脉血,检测其血清FBG、FTNS、瘦素、HOMA、TNF-α、MDA及血脂水平。结果:与对照组相比,其余各组FBG、FINS、瘦素水平及HOMA-IR均明显升高(P0.05);心肌梗死组及大、中、小剂量瘦素预处理组FBG及瘦素水平与假手术组相比均明显升高,心肌梗死组、高剂量瘦素预处理组FINS及HOMA-IR与之相比亦明显升高,小、中剂量瘦素预处理组FINS及HOMA-IR与之相比均明显降低(P0.05);小、中剂量瘦素预处理组FBG、FINS、瘦素水平及HOMA-IR与心肌梗死组相比均明显降低(P0.05)。与对照组相比,其余各组大鼠TNF-α、MDA水平均明显升高(P0.05);与假手术组相比,心肌梗死组、大、中、小剂量组大鼠TNF-α、MDA水平明显升高(P0.05);与心肌梗死组相比,中、小剂量组大鼠TNF-α、MDA水平均明显降低(P0.05)。与对照组相比,其余各组大鼠TG、TC、LDL-C水平均明显升高,HDL-C水平均明显降低(P0.05);大、中、小剂量组HDL-C值与假手术组相比均明显升高,TG、TC、LDL-C值与之相比均明显降低(P0.05);与心肌梗死组相比,小、中剂量组大鼠TG、TC、LDL-C水平均明显降低(P0.05),HDL-C水平均明显升高(P0.05)。结论:瘦素预处理能够保护糖尿病大鼠心肌缺血再灌注损伤,可能与其减轻炎症、氧化应激、血脂紊乱及胰岛素抵抗有关。