Anti-inflammatory and anti-oxidant properties of Sida rhombifolia stems and roots in adjuvant induced arthritic rats

Free radical stress leads to tissue injury and progression of disease conditions such as arthritis, hemorrhagic shock, atherosclerosis, diabetes, hepatic injury, aging and ischemia, reperfusion injury of many tissues, gastritis, tumor promotion, neurodegenerative diseases and carcinogenesis. Safer anti-oxidants suitable for long term use are needed to prevent or stop the progression of free radical mediated disorders. Herbal medicine provides a foundation for various traditional medicine systems worldwide. The Sida species is one of the most important families of medicinal plants in India. Hence, the present study was aimed to investigate the possible anti-oxidant potential of Sida rhombifolia extracts for 30 days on adjuvant induced arthritis in experimental rats. The altered levels of hematological parameters were reverted to near normal levels, especially the elevated rate of erythrocyte sedimentation was significantly reduced by S. rhombifolia extracts in experimental rats. Oral administration of root and stem of S. rhombifolia extracts significantly increased the levels of thiobarbituric acid reactive substances and activities of catalase and glutathione peroxidase and decreased the levels of reduced glutathione and superoxide dismutase activity in arthritis induced rats. The free radical scavenging activity of the plant was further evidenced by histological and transmission electron microscopy observations made on the hind limb tissue.     

Gastric toxicity of racemic ketoprofen and its enantiomers in rat: Oxygen radical generation and COX-expression

Objective and design The gastric toxicity of racemic-ketoprofen and its enantiomers (S(+)− and R(−)−ketoprofen), oxygen free radical generation and neutrophil infiltration in response to damage were evaluated in rats. Changes in prostaglandin synthesis, cyclooxygenase expression and glutathione metabolism were also studied. Materials and methods Studies were performed in Wistar rats. Drugs were given by oral administration: racemic-ketoprofen (100, 50 and 25 mg/kg body weight); S(+) and R(−)−ketoprofen (50, 25 and 12.5 mg/kg body weight). Determinations were made of gastric mucosal injury, lipid peroxidation, xanthine oxidase, myeloperoxidase and superoxide dismutase activities, glutathione levels, glutathione peroxidase and glutathione reductase activities, gastric prostaglandin synthesis (PGE₂ levels) and COX-expression. Results Racemic-ketoprofen dose-dependently exhibited the highest toxicity. In contrast, S(+)−ketoprofen at half the dose of the racemic compound proved to be less ulcerogenic. R(−)−ketoprofen was also less ulcerogenic, but when administered as the racemate exacerbated gastric ulcération caused by S(+)−ketoprofen. Drug administration produced significant increases in lipid peroxidation levels and xanthine-oxidase and a decrease in Superoxide dismutase activity. Nevertheless the racemate induced the highest disturbances in oxidative metabolism. No changes in myeloperoxidase values and glutathione metabolism were found. Cyclooxygenase-1 immunoreactivity was observed and did not differ from that in control rats. Cyclooxygenase-2 could also be expressed after treatments.     

Effects of meloxicam on oxygen radical generation in rat gastric mucosa

AIM AND DESIGN: In addition to a deficiency of endogenous prostaglandins due to inhibition of cyclo-oxygenase and a host of prostaglandin-mediated effects on mucosal protection, it has recently been proposed that neutrophil- and oxygen radical - dependent microvascular injuries may be important prime events that lead to mucosal injury induced by non-steroidal anti-inflammatory drugs. Therefore, we evaluated the role of oxygen free radicals in the pathogenesis of acute gastric ulceration induced by meloxicam, a preferential COX-2 inhibitor. MATERIAL: Studies were performed in Wistar rats. Treatment: Meloxicam was given by oral administration (3.75-30 mg/kg body weight). METHODS: Determinations were made of gastric mucosal injury, xanthine-oxidase, myeloperoxidase and superoxide dismutase activities, as well as the effect of meloxicam on gastric prostaglandin synthesis (PGE2 levels) and glutathione homeostasis. RESULTS: Oral administration of meloxicam dose-dependently (3.75-30 mg/kg) caused acute gastric haemorrhage erosions. The total area of gastric lesions increased with time until 24 hours after dosing. Xanthine-oxidase activity increased significantly after administration of the drug. Myeloperoxidase activity, as an index of neutrophil infiltration, as well as glutathione peroxidase, an important enzyme that scavenges lipid peroxides, were unaffected by meloxicam administration. In addition, superoxide dismutase activity, PGE2 and glutathione levels were significantly reduced. CONCLUSION: These results support the hypothesis that in addition to suppression of prostaglandin synthesis, oxygen free radicals, probably derived via the action of xanthine oxidase, the decrease in superoxide dismutase activity, and the depletion of mucosal glutathione contribute to the pathogenesis of meloxicam-induced ulceration.     

Monocytes and neutrophils oxidize low density lipoprotein making it cytotoxic

Free radicals are believed to be involved in leukocyte induced tissue injury. The present studies were performed to determine whether low density lipoprotein (LDL) might serve as a mediator of tissue injury after leukocyte induced free radical oxidation of LDL. Our results show that incubation of LDL with monocytes or polymorphonuclear leukocytes (PMN) leads to oxidation of the lipoprotein rendering it toxic to proliferating fibroblasts. Monocyte activation enhances these effects. Butylated hydroxytoluene (BHT), vitamin E (vit E) and glutathione (GSH) virtually prevent the oxidation of LDL and the formation of cytotoxic LDL, indicating that these alterations are mediated by leukocyte-derived free radicals. This is the first demonstration that short-lived free radicals emanating from phagocytic cells could mediate cell injury through the action of a stable cytotoxin formed by the oxidation of LDL. The fact that lipoproteins can transfer a cytotoxic effect from leukocytes to proliferating cells reveals a pathway for cell destruction which may have implications in atherosclerotic plaque progression, macrophage mediated toxicity to tumor cells and tissue injury by inflammatory processes.     

Antioxidant status in delayed healing type of wounds

This investigation studied the contribution of antioxidants in delaying healing in excision cutaneous wounds (8 mm) in diabetic, aged and immunocompromised animals. Skin levels of catalase, glutathione (GSH), ascorbic acid (AA) and vitamin E in streptozotocin-induced diabetic rat were lower as compared to nondiabetics. The 7-d wound tissue of diabetic rats showed an increased vitamin E level along with depleted GSH content. In aged rats (18 months old), higher levels of skin superoxide dismutase (SOD), glutathione peroxidase (Gpx) and thiobarbituric acid reactive substances (TBARS) and lower levels of catalase and GSH were found as compared to their values in young rats (3-4 months old). The levels of SOD, GPx, catalase, AA, GSH and vitamin E in 7-d wound tissue of aged rats were significantly lower in comparison to those in young rats. However, TBARS were elevated in these wound tissues. The non-wounded skin of immunocompromised (athymic) mice showed lower levels of SOD, catalase, and TBARS and higher GSH and GPx levels in comparison to those present in normal mouse skin. Surprisingly, the analysis of 7-d wound tissue showed higher levels of SOD, catalase, GPx, and GSH and lower TBARS level in athymic mice compared to the wound tissue of normal mice. Thus low levels of antioxidants accompanied by raised levels of markers of free radical damage play a significant role in delaying wound healing in aged rats. In diabetic rats reduced glutathione levels may have a contributory role in delaying the healing process. However, in immunocompromised mice the antioxidant status following injury showed an adapted response.     

Increasing sympathetic nerve terminal-dependent plasma extravasation correlates with decreased arthritic joint injury in rats

This study compared the pharmacology of adrenergic agents that influence plasma extravasation in normal animals with those agents that influence tissue injury in an inflammatory disease model. Specifically we studied the effects of beta 2- and alpha 2-adrenergic receptor agonists and antagonists on bradykinin-induced plasma extravasation in normal Sprague-Dawley rats and on joint injury in rats with experimental arthritis. Plasma extravasation induced by infusion of bradykinin in the rat knee joint was attenuated by the beta 2-agonist salbutamol or by the alpha 2-antagonist yohimbine, and was enhanced by the beta 2-antagonist, ICI-118,551, or by the alpha 2-agonist, clonidine. In rats that had undergone chemical symphathectomy, bradykinin-induced plasma extravasation was markedly reduced, and there was no enhancement of bradykinin-induced plasma extravasation by either ICI-118,551 or clonidine. Although ICI-118,551 and clonidine enhanced bradykinin-induced plasma extravasation, these drugs significantly reduced joint injury in rats with adjuvant-induced arthritis. Neither salbutamol nor yohimbine, however, significantly increased joint injury in the arthritic rats, presumably because arthritis severity is already high in these animals. Consistent with this hypothesis, both salbutamol and yohimbine did significantly increase the joint injury associated with experimental arthritis in Wistar-Kyoto rats, a strain which develops a mild adjuvant arthritis. The fact that increased plasma extravasation is associated with decreased arthritis severity suggests that plasma extravasation, a major sign of acute inflammation, contributes to tissue reparative processes.     

补充VA、VE对梭曼中毒大鼠体内抗氧化能力影响的初探

目的 研究梭曼对急性中毒大鼠的自由基损伤作用,探讨维生素A、E的抗氧化作用。方法 雄性大鼠,随机分为对照组、阳性组、VA组、VE组。灌胃10d,第11d除阴性组外其余各组大鼠均皮下注射0．9LD50梭曼,2h后取样,测定各组全血和肝组织的谷胱甘肽过氧化物酶（GSH－Px)、过氧化氢酶（CAT）、VE和总抗氧化力（T－AOC）。结果 梭曼中毒2h后,GSH－Px活性、T－AOC水平、VE含量降低。维生素A、E均有效的抑制其变化。结论 梭曼对大鼠有自由基损伤作用,维生素A、E对梭曼中毒大鼠过氧化损伤具有保护作用,提示维生素A、E对梭曼中毒有预防作用。     

Effects of diethyldithiocarbamate on life span, metabolic rate, superoxide dismutase, catalase, inorganic peroxides and glutathione in the adult male housefly, Musca domestica

The effect of inactivation of superoxide dismutase, by diethyldithiocarbamate, on life span, metabolic rate, superoxide dismutase activity, catalase activity, inorganic peroxide concentration and glutathione levels in adult male houseflies was determined. The general objective was to examine the role of free radical defenses in the aging process. Houseflies were administered 0. 1 and 10 mM diethyldithiocarbamate in their drinking water. Administration of diethyldithiocarbamate caused an extension in the average life spans of the populations while the metabolic rates were depressed. Superoxide dismutase activity was significantly reduced. Inorganic peroxide concentration and catalase activity declined in rough correspondence to the decrease in the metabolic rate. The levels of reduced glutathione were significantly elevated whereas oxidized glutathione concentrations remained relatively unaffected. The results are interpreted to indicate that a decrease in superoxide dismutase activity in the housefly, by diethyldithiocarbamate administration, is compensated by an elevation in reduced glutathione levels and reduction of oxygen consumption, suggesting the existence of alternative free radical defenses in vivo.     

Reactive oxygen metabolites and anti-oxidative defenses in aspirin-induced gastric damage in rats: Gastroprotection by Vitamin E

OBJECTIVE: It has been proposed that neutrophil infiltration and oxygen radicals may be the important prime events that lead to mucosal injury induced by aspirin. Vitamin E acts as a potent antioxidant, and is capable of scavenging free radicals. The aim of this study was to evaluate the oxygen metabolites and anti-oxidative defenses in acute gastric damage induced by aspirin and to find the effects of Vitamin E. METHODS: Ninety-six Wistar rats were divided into four groups of 24 rats each as follows: (1) the control group; (2) the ASA group that received 300mg/kg of ASA; (3) the Vitamin E plus ASA group and (4) the Vitamin E group that received Vitamin E (75 units) alone. At 3, 6, 9 and 24h after the drug administration, six rats were randomly selected from each group and gastric mucosal injury, prostaglandin E2, and the activities of myeloperoxidase, xanthine-oxidase, superoxide dismutase, glutathione peroxidase as well as glutathione level were measured and compared between the groups. RESULTS: Oral administration of ASA caused acute gastric erosions and an increase in myeloperoxidase activity. It also decreased prostaglandin E2, superoxide dismutase activity, glutathione peroxidase activity and glutathione level. Concomitant administration of Vitamin E and ASA restored all the changes toward the control levels. CONCLUSION: Free radicals and suppression of anti-oxidizing enzymes play important roles in gastric damage induced by aspirin. Increased myeloperoxidase activity suggests that activated neutrophils may be a major source of free radicals. Vitamin E protects against ASA-induced damage due to its anti-oxidizing activity.     

Aqueous extract of Terminalia arjuna prevents cyclosporine-induced renal disorders

Cyclosporine (CsA), a powerful immunosuppressant, had a significant impact on transplantation medicine, and exposure to this chemical is known to induce oxidative stress and causes renal injury by the formation of free radicals. Acute and chronic renal damage are very common pathophysiologic disturbances caused by CsA. The present study has been conducted to evaluate the protective role of the aqueous extract of the bark of Terminalia arjuna (TA), an important Indian medicinal plant widely used in the preparation of ayurvedic formulations, on CsA-induced oxidative stress and resultant dysfunction in the rat kidney. Animals were treated with the aqueous extract of TA (100 mg/kg body weight (b.wt)) and then treated with CsA (25 mg/kg b.wt) in olive oil for 14 days. The level of urea, uric acid, and creatinine was determined from serum sample. The enzymes, namely, alkaline phosphatase (ALP), acid phosphatase (ACP), aspartate transaminase (AST), and alanine transaminase (ALT), and enzymic indices of membrane integrity such as Na⁺K⁺ATPase, Ca²⁺ATPase, and Mg²⁺ATPases were estimated in the tissue of all study groups. Antioxidant status in kidney tissues was estimated by determining the activities of the antioxidative enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione transferase (GST) and the levels of reduced glutathione, vitamin E, and vitamin C. In addition, the kidney phospholipids, cholesterol, triglycerides, and free fatty acids were determined in the tissue. Results showed that CsA caused a marked increase in the levels of urea, uric acid, and creatinine in serum and decreases the levels of ALP, ACP, AST, ALT, Na⁺K⁺ATPase, Ca²⁺ATPase, Mg²⁺ATPases, SOD, CAT, glutathione reductase, GST, GPx, vitamin E, and vitamin C whereas cholesterol, triglycerides, free fatty acid, and phospholipid levels were found to be increased in the kidney tissue homogenates of CsA-treated rats. Aqueous extract of TA successfully prevented the alterations of these effects in the experimental animals. Data also showed that the extract possessed strong free radical scavenging activity comparable to that of vitamin C. Our study demonstrated that the aqueous extract of the bark of TA could protect the kidney tissues against CsA-induced oxidative stress probably by increasing antioxidative defense activities.     

Protective effect of Sonchus asper extracts against experimentally induced lung injuries in rats: A novel study

In this study, protective effects of methanol extract (SAME) were evaluated against carbon tetrachloride induced oxidative stress in lungs. Male Sprague–Dawley rats were orally fed with various doses (100, 200 mg/kg body weight) of SAME and (50 mg/kg body weight) of rutin after 48 h of CCl₄ treatment (3 ml/kg body weight, 30% in olive oil) biweekly for 4 weeks. The results showed that administration of extracts and rutin significantly restored lung contents of reduced glutathione and activities of catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, quinine reductase were reduced while lipid peroxide, hydrogen peroxide, nitrite, DNA fragmentation% and activity of γ-glutamyl transferase, increased by CCl₄, were reversed towards the control levels by the supplement of Sonchus asper extracts and rutin. Lung histopathology showed that S. asper extracts and rutin reduced the incidence of lung lesions induced by CCl₄ in rats. These results suggest that S. asper fractions and rutin could protect lung against the CCl₄-induced oxidative damage in rats.     

Macrophage, lymphocyte and chronic inflammatory responses in selenium deficient rodents. Association with decreased glutathione peroxidase activity

The influence of a selenium deficient diet in mice and rats has been studied on glutathione peroxidase (GSH-Px) and secretory activities of peritoneal macrophages, mitogenesis of spleen cells and adjuvant arthritis. Macrophage GSH-Px activity was significantly reduced from 9 weeks on the selenium deficient diet. This reduction was associated with enhanced macrophage H2O2 release on zymosan stimulation after 12 weeks on the diet, a similar trend in chemiluminescence and reduced mitogenesis of spleen cell cultures to T and B cell mitogens after 8 weeks on the diet. Macrophage beta-glucuronidase release was not significantly altered. Phorbol myristic acetate induced macrophage H2O2 generation was reduced by selenium deficiency, possibly due to increased cellular damage. Adjuvant arthritis of rats was significantly enhanced after 6 and 12 weeks on the selenium deficient diet. The enhanced release of H2O2 by macrophages after zymosan stimulation can be directly attributable to loss of GSH-Px activity leading to reduced peroxide breakdown. Peroxide-mediated cell injury would also account for the reduction in lymphocyte mitogenesis and enhancement of adjuvant arthritis. These data provide support for a role of selenium in immune and inflammatory responses.     

依达拉奉对脑外伤后大鼠的神经保护作用

目的研究自由基清除剂依达拉奉对大鼠颅脑外伤的保护作用。方法将SD大鼠分为依达拉奉组(n=32)和对照组(n=32)。利用自制自由落体撞击装置,制作脑外伤模型。撞击前30min及伤后3h尾静脉给药。分4个时间点于外伤后6h、24h、3d、7d分别处死实验组和对照组。TUNEL法检测凋亡,免疫组化法分析8-羟基-脱氧鸟苷。结果外伤后初期依达拉奉对大鼠生理指标没有明显的影响(P>0.05);但依达拉奉治疗后的脑外伤大鼠相对对照组神经功能评分明显减少(P<0.05);神经元的凋亡情况也有显著的减少(P<0.05),同时显著减少外伤后脑组织中8-羟基-脱氧鸟苷含量(P<0.05)。结论依达拉奉对脑外伤大鼠有很好的神经保护作用,其作用机制可能与清除氧自由基,减轻脑水肿有关。     

蝉拟青霉总多糖对免疫抑制大鼠组织器官免疫功能调节的实验研究

目的：观察蝉拟青霉总多糖对免疫抑制大鼠组织器官免疫功能调节和自由基代谢的影响，探讨其对免疫抑制大鼠组织器官的免疫调节和抗衰老作用。 方法： 以速率法在全自动生化分析仪上测定乳酸脱氢酶（LDH）活力；以鸟氨酸的生成判断精氨酸酶(arginase)的活力；以硫代巴比妥酸-醋酸法测定脂质过氧化物(LPO)含量；以Ellman试剂测定还原型谷胱甘肽(GSH)水平。 结果： 蝉拟青霉总多糖使环磷酰胺所致免疫抑制大鼠组织细胞内LDH（肾、胸腺）、arginase（肝、脾、胸腺）活力升高，具有显著差异（均P<0.01）；使LPO（肾、脾、胸腺）的含量下降（P<0.05或P<0.01）；使环磷酰胺所致的肝、脾内低下的还原型谷胱甘肽(GSH)升高（均P<0.01）。 结论： 蝉拟青霉总多糖能增强免疫抑制大鼠组织器官的免疫功能和加速自由基的代谢。     

Embryopathy in experimental diabetic gestation: assessment of oxidative stress and antioxidant defence

Maternal diabetes is associated with an increased rate of congenital fetal anomaly. In the present study, diabetes was induced by streptozotocin in female rats one week prior to conception and the embryos were examined during organogenesis. Experimental diabetes is associated with over-production of free radicals and disturbed antioxidant defence, particularly in malformed embryos. Oxidative stress is demonstrated by increased MDA accumulation and reduced glutathione levels. Despite large differences in the reduced/oxidised glutathione ratios during organogenesis in the control, diabetic non-malformed and malformed embryo groups, the half-cell redox potential was constant for each group during the experimental period. Calculated redox potentials indicated that although embryo cells from the control and diabetic mother groups were of the same chronological age, the stages of development were different. Increased oxidative stress in rat embryos was associated with increased glutathione peroxidases and glutathione-S-transferase activity. This may, in part, provide an explanation for the observed accumulation of oxidised glutathione in malformed embryos. Moreover, decreased levels of vitamin C and selenium were observed. Increased oxidative stress and perturbations in antioxidant defence contribute to the high incidence of congenital anomalies in experimental diabetic gestation.     

Toxicity assessment and analgesic activity investigation of aqueous acetone extracts of Sida acuta Burn f. and

ABSTRACT: BACKGROUND: Sida acuta Burn f. and Sida cordifolia L. (Malvaceae) are traditionally used in Burkina Faso to treat several ailments, mainly pains, including abdominal infections and associated diseases. Despite the extensive use of these plants in traditional health care, literature provides little information regarding their toxicity and the pharmacology. This work was therefore designed to investigate the toxicological effects of aqueous acetone extracts of Sida acuta Burn f. and Sida cordifolia L. Furthermore, their analgesic capacity was assessed, in order to assess the efficiency of the traditional use of these two medicinal plants from Burkina Faso. METHOD: For acute toxicity test, mice were injected different doses of each extract by intraperitoneal route and the LD50 values were determined. For the subchronic toxicity evaluation, Wistar albinos rats were treated by gavage during 28 days at different doses of aqueous acetone extracts and then haematological and biochemical parameters were determined. The analgesic effect was evaluated in mice by the acetic-acid writhing test and by the formalin test. RESULTS: For the acute toxicity test, the LD50 values of 3.2 g/kg and 3.4 g/kg respectively for S. acuta Burn f. and S. cordifolia L. were obtained. Concerning the haematological and biochemical parameters, data varied widely (increase or decrease) according to dose of extracts and weight of rats and did not show clinical correlations. The extracts have produced significant analgesic effects by the acetic acid writhing test and by the hot plate method (p <0.05) and a dose-dependent inhibition was observed. CONCLUSION: The overall results of this study may justify the traditional uses of S. acuta and S. cordifolia .     

The free radical scavenger edaravone suppresses experimental closed duodenal loop-induced acute pancreatitis in rats

Recent studies suggest that the enhanced release of reactive oxygen species (ROS) plays an important role in the pathogenesis of clinical acute pancreatitis. In the present study, we investigated the effects of the free radical scavenger edaravone, which is used clinically as an anti-stroke agent, in the development of experimental closed duodenal loop (CDL)-induced acute pancreatitis. In the CDL-pancreatitis model, after edaravone and vehicle saline were injected intravenously, pancreatitis was induced for 7 h by the CDL technique. The subsequent ascites volume, wet pancreatic weight, serum amylase levels, and pancreatic tissue lipid peroxide levels were evaluated. Pancreatic tissue damage was also evaluated histologically. In this CDL-induced pancreatitis model, edaravone treatment tended to reduce the ascites volume and inhibit the increases in the wet pancreatic weight. Edaravone also tended to reduced the microscopic mucosal damage scores and pancreatic tissue lipid peroxide levels. In particular, the serum amylase levels in the edaravone-treated rats (1-20 mg/kg i.v.) were significantly reduced as compared to the vehicle-treated rats. These results strongly support the involvement of ROS in the pathogenesis of CDL-induced acute pancreatitis and cytoprotective effects of free radical scavender against pancreatic acinar cells. A clinical effect for edaravone against acute pancreatitis is strongly expected.     

Glutathione status and reactive oxygen generation in tissues of young and old exercised rats

The effects of exercise on the generation of active oxygen species and radical-scavenging capacity were studied in physically active and sedentary young and old rats. Exercise increased the hydroxyl radical content in all tissues of physically active young rats, except in the plasma. In old rats, the basal level of the radical increased significantly in plasma, heart, and skeletal muscles, but decreased in liver; and physical activity decreased it to that of young rats in most cases. With exercise, the content of reduced glutathione increased in plasma, heart, and skeletal muscles of young rats, whereas that of oxidized glutathione markedly decreased in liver and increased in brain and white gastrocnemius muscle. The total glutathione levels in these tissues changed in a similar way, indicating that glutathione was released from the pool in the liver. In rats allowed to run voluntarily for 5 weeks, the effects were more pronounced than in the sedentary rats. The ratio of reduced to total glutathione, which indicates the capacity to reduce glutathione, increased in plasma, heart, and soleus muscle of sedentary young rats after exercise, and increased further in those undergoing physical activity. In old rats, the reduced glutathione level increased in plasma, heart, liver, and brain, even though the total decreased. These results suggest that physical activity enhances the endogenous ability to defend against oxidative stress. In old rats, even though glutathione synthesis is decreased, the regenerating capacity seems to be increased in order to compensate for the increased oxidative stress.     

老龄大鼠脑缺血再灌注ATP酶和自由基代谢变化及其意义

目的:从ATP酶活性变化和自由基损伤方面研究老龄大鼠脑缺血再灌注损伤的机制。方法:青年(5月龄)和老龄(20月龄以上)大鼠均分为模型组和正常对照组,观察大鼠全脑缺血30min再灌注60min后ATP酶和SOD活性及MDA、Ca^2＋、Na^＋、K^＋含量。结果:老龄模型组Ca^2＋水平高于青年模型组和老龄对照组。老龄对照组脑组织Na^＋-K^＋-ATP酶低于青年对照组,老龄模型组低于青年模型组。老龄对照组Ca^2＋-ATP酶低于青年对照组,老龄模型组低于青年模型组但高于老龄对照组。老龄对照组血清和脑组织中SOD活性低于青年对照组,老龄模型组低于青年模型组。老龄模型组血清和脑组织MDA/SOD比值高于老龄对照组。结论:脑缺血再灌注损伤与钙超载和自由基损伤有关,但由于老龄大鼠脑组织ATP酶和钙含量及自由基代谢的增龄变化,使脑缺血再灌注后这些病理改变较青年大鼠更为明显并具有一定特点。     

Induction of a neurite-promoting factor in rat brain following injury or deafferentation

Ablation of the entorhinal/occipital cortex in young adult rats caused a several-fold increase in the neurite-promoting activity in extracts of the tissue surrounding the wound and in areas that had been deafferented by the lesion. The time course of induction closely paralleled reactive axon sprouting in the deafferented hippocampus, with maximal levels of neurite-promoting activity reached between 9 and 15 days post-lesion. Aged animals, in which reactive sprouting is deficient, showed no increase in activity by 12 days after deafferentation of the hippocampus. The neurite-promoting activity of brain extracts was non-diffusible, heat-labile, and sensitive to proteolysis. All of the activity bound to diethylaminoethyl (cellulose) and was eluted at 200 mM NaCl. The apparent molecular weight (by gel filtration) of the activity in extracts of uninjured brain was 9-17 kilodaltons, whereas the extracts of injured brain also had peaks or shoulders at 30, 70 and greater than or equal to 200 kilodaltons. These data suggest that the brain neurite-promoting activity resides in one or more proteins. Both the injury-induced and basal activities were different from laminin, nerve growth factor, and polyornithine-bindable neurite-promoting factors. The injury-induced activity was sensitive to repeated freezing and thawing, but this inactivation was reversed by thiol reagents such as glutathione, thioglycerol, and mercaptoethanol. We report a neurite-promoting factor that is induced following brain injury or denervation, and may also be important for reactive axon sprouting after brain injury. The induction of this factor is abnormal in aged animals, as is the reactive sprouting response. The properties of the injury-induced activity distinguish it from the basal activity (found in uninjured brain) and from other characterized neurite-promoting factors.