Oxidative Injury In Rats Research Articles

Effect of Curcuma kwangsiensis polysaccharides on blood lipid profiles and oxidative stress in high-fat rats

We have investigated the protective effect of polysaccharides from Curcuma kwangsiensis (CKP) against oxidative injury in rats fed high-fat diet. The protective effect of CKP was compared with Lovastatin, a well-known antioxidant. Sixty SD rats were used for the experimental study. Oxidative injury was induced by feeding high-fat diet for 3 weeks. The blood profiles, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-c) levels during experimental period were significantly increased in untreated model control group, whereas high-density lipoprotein cholesterol (HDL-c) levels and antioxidant enzymes activities significantly decreased in untreated model control group. The levels of TC, TG, LDL-c levels in CKP-treated rats were decreased significantly when compared to the untreated model control group, which were brought down to near normal in CKP-treated group. HDL-c level and antioxidant enzymes activities were found to be significantly increased in serum of CKP-treated group compared to the untreated model control group. The protective effect of CKP against oxidative injury was comparable to that of Lovastatin. Our data suggest that CKP exerts its protective effect by modulating the extent of lipid peroxidation and augmenting antioxidant defense system and thus protects the experimental animals against oxidative injury induced by high-fat diet treatment.

Combined administration of taurine and monoisoamyl DMSA protects arsenic induced oxidative injury in rats.

Arsenic is a naturally occurring element that is ubiquitously present in the environment. High concentration of naturally occurring arsenic in drinking water is a major health problem in different parts of the world. Despite arsenic being a health hazard and a well documented carcinogen, no safe, effective and specific preventive or therapeutic measures are available. Among various recent strategies adopted, administration of an antioxidant has been reported to be the most effective. The present study was designed to evaluate the therapeutic efficacy of monoisoamyl dimercaptosuccinic acid (MiADMSA), administered either individually or in combination with taurine post chronic arsenic exposure in rats. Arsenic exposed male rats (25 ppm, sodium arsenite in drinking water for 24 weeks) were treated with taurine (100 mg/kg, i.p., once daily), monoisoamyl dimercaptosuccinic acid (MiADMSA) (50 mg/kg, oral, once daily) either individually or in combination for 5 consecutive days. Biochemical variables indicative of oxidative stress along-with arsenic concentration in blood, liver and kidney were measured. Arsenic exposure significantly reduced blood delta-aminolevulinic acid dehydratase (ALAD) activity, a key enzyme involved in the heme biosynthesis and enhanced zinc protoporphyrin (ZPP) level. Clinical hematological variables like white blood cells (WBC), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) showed significant decrease with a significant elevation in platelet (PLT) count. These changes were accompanied by significant decrease in superoxide dismutase (SOD) activity and increased catalase activity. Arsenic exposure caused a significant decrease in hepatic and renal glutathione (GSH) level and an increase in oxidized glutathione (GSSG). These biochemical changes were correlated with an increased uptake of arsenic in blood, liver and kidney. Administration of taurine significantly reduced hepatic oxidative stress however co-administration of a higher dose of taurine (100 mg/kg) and MiADMSA provided more pronounced effects in improving the antioxidant status of liver and kidney and reducing body arsenic burden compared to the individual treatment of MiADMSA or taurine. The results suggest that in order to achieve better effects of chelation therapy, co-administration of taurine with MiADMSA might be preferred.

Neuroprotective effects of thymoquinone against transient forebrain ischemia in the rat hippocampus

Increasing evidence demonstrates that oxidative stress plays an important role in brain injury in experimental models of brain ischemia. Thymoquinone, the main constituents of the volatile oil from Negella sativa seeds, is reported to possess strong antioxidant properties. Hence, the present study was undertaken to evaluate the neuroprotective effect of thymoquinone against transient forebrain ischemia-induced neuronal damage in the rat hippocampus. Rats were divided randomly into five groups: control, sham, ischemia, thymoquinone and ischemia+thymoquinone. Transient forebrain ischemia was induced with bilateral occlusion of both common carotid arteries for 10 min followed by 7 days of reperfusion. Thymoquinone was administered (5 mg/kg/day p.o.) 5 days before ischemia and continued during the reperfusion time. Animals were sacrificed, and brain tissues were isolated for histopathological examination. Hippocampal tissues were also used for determination of malondialdehyde levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant and the activities of the antioxidant enzymes catalase and superoxide dismutase (SOD). Thymoquinone and its metabolite thymohydroquinone were tested as inhibitors of the in vitro non-enzymatic lipid peroxidation induced by iron-ascorbate in the hippocampal homogenate. Forebrain ischemia–reperfusion neural injury in rats was demonstrated by histopathological observation, which revealed significant neural cell death in the hippocampus CA1 area 7 days post-ischemia (77% cell loss). Additionally, forebrain ischemia–reperfusion oxidative injury in rats was demonstrated by a significant increase in malondialdehyde and a significant decrease in GSH contents, catalase and SOD activities in the hippocampal tissue compared to the control or sham-operated groups. Pretreatment of thymoquinone attenuated forebrain ischemia-induced neuronal damage manifested by significantly decreasing the number of dead hippocampal neuronal cells (24% in thymoquinone-treated versus 77% for ischemia, P<0.001), which confirm the protective role of thymoquinone in ischemia–reperfusion injury. Also, pretreatment of ischemic rats with thymoquinone decreased the elevated levels of malondialdehyde and increased GSH contents, catalase and SOD activities to normal levels. Thymoquinone and thymohydroquinone inhibited the in vitro non-enzymatic lipid peroxidation in hippocampal homogenate induced by iron-ascorbate. The IC50 for thymoquinone and thymohydroquinone were found to be 12 and 3 μM respectively. This suggests that the protection of thymoquinone and its metabolite involve increased resistance to oxidative stress. In conclusion, thymoquinone is effective in protecting rats against transient forebrain ischemia-induced damage in the rat hippocampus. This spectacular protection makes thymoquinone a promising agent in pathologies implicating neurodegenaration such as cerebral ischemia.

Prevention of Cerebral Oxidative Injury by Post-ischemic Intravenous Administration of Shengmai San

Shengmai San (SMS) is a traditional Chinese medicine (TCM) comprising three different herbal components, Panax ginseng, Ohiopogon japonicus and Fructus schisandrae and has been used for treating coronary heart diseases (Bensky and Barolet, 1990). It was shown that SMS effectively prevented cerebral oxidative injury in rats when it administered into the duodenum before cerebral ischemia-reperfusion. In the present study, we examined whether post-ischemic administration of SMS can ameliorate cerebral ischemia-reperfusion injury in rats as well. Results showed that SMS injected immediately after ischemia also prevented the ischemia-reperfusion injury, when the effect was evaluated by the formation of protein carbonyl and thiobarbituric acid reactive substance (TBARS), and the loss of glutathione peroxidase (GPX). The preventative potential of SMS was decreased rapidly dependent on the time lag until SMS was injected after ischemia. However, it was noted that intravenously administered SMS protected the oxidative injury approximately 30% even after 60 min of reperfusion in terms of protein carbonyl formation. It is thus suggested that SMS injection might be useful for preventing the progression of injury in cerebral infarction after stroke.

Beneficial role of monoesters of meso-2,3-dimercaptosuccinic acid in the mobilization of lead and recovery of tissue oxidative injury in rats

We investigated the therapeutic efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) and two of its analogues, monomethyl dimercaptosuccinic acid (MmDMSA) and mono-cyclohexyl dimercaptosuccinic acid (MchDMSA) in reducing lead concentration in blood and soft tissues, and in recovering lead induced oxidative stress in rats. Male wistar rats were exposed to lead acetate in drinking water for 20 weeks, followed by 5 days of oral treatment with DMSA (100 mg/kg, oral, once daily), MmDMSA or MchDMSA (50 and 100 mg/kg). Biochemical variables indicative of oxidative stress along with lead, zinc and copper concentration were evaluated in blood and other soft tissues. Exposure to lead caused a significant decrease in blood δ-aminolevulinic acid dehydratase (ALAD) activity and glutathione (GSH) level. These changes were accompanied by inhibition of kidney ALAD and an increase in δ-aminolevulinic acid synthatase (ALAS) activity in liver and kidneys. Also seen were a pronounced depletion of brain GSH, glutathione peroxidase (GPx), glutathione- S-transferase (GST) and decreased superoxide dismutase (SOD) activity and an increase in thiobarbituric acid reactive substances (TBARS) and reactive oxygen species (ROS) levels. These biochemical changes were correlated with an increased uptake of lead in blood and soft tissues. Blood and kidneys zinc concentration decreased significantly following lead exposure while, copper concentration remained unchanged. No effect of chelation on hepatic zinc concentration was noted, only liver copper concentration showed significant depletion on treatment with DMSA and MmDMSA (100 mg/kg). Treatment with DMSA, MmDMSA and MchDMSA provided significant recovery in altered biochemical variables and brain DNA damage besides significant depletion of tissue lead burden. Among the chelating agents used, MchDMSA and MmDMSA provided better recovery in altered biochemical variables and depletion of lead concentration in tissues compared to DMSA. The above results suggest DMSA monoesters to be a better treatment option than DMSA in eliciting recovery to the altered biochemical variables and in the depletion of body lead burden.

Preoperative feeding preserves heart function and decreases oxidative injury in rats

Objective The nutritional status of a patient has been implicated as an important factor in the development of postoperative complications. Fasting before an operation may have detrimental effects on the metabolic state. We hypothesized that there was a positive correlation between preoperative nutritional status and postoperative organ function. Methods Preoperative feeding was compared with fasting with respect to effects on organ function and biochemical parameters in an animal model of extensive large abdominal surgery. Male Wistar rats were fed ad libitum or fasted for 16 h, after which the arteria mesenterica superior was clamped for 60 min followed by 180 min of reperfusion. Results After the ischemic period, heart function was significantly better in animals that were fed ad libitum than in fasted animals. Moreover, after intestinal ischemia and reperfusion, fed rats showed significantly higher levels of intestinal adenosine triphosphate and a significantly higher malondialdehyde concentration in the intestine and lung than did fasted rats. The ratio of adenosine triphosphate to adenosine diphosphate in the liver, an indicator of energy status, in fed rats was similar to that in a sham group, whereas fasted animals showed a significantly lower value. Conclusions Preoperative nutrition in contrast to fasting may attenuate ischemia/reperfusion-induced injury and preserve organ function in the rat.

Phenolic compositions of Viburnum dilatatum Thunb. fruits and their antiradical properties

The fruit of Viburnum dilatatum Thunb., called “gamazumi” in Japanese, has been shown to prevent oxidative injury in rats given gamazumi crude extract (GCE), a solid which was obtained from the squeezed juice. Crude protein and fat contents were very low in the squeezed juice, and GCE included 53.0 mg/g of total polyphenols. Therefore, five major phenolic compounds were isolated from GCE, which they were identified by NMR and liquid chromatography/mass spectrometry/MS. These chemical structures were as follows: cyanidin 3-sambubioside (Cy-3-sam), cyanidin 3-glucoside (Cy-3-glc), 5- O-caffeoyl-4-methoxyl quinic acid (4-MeO-5-CQA), quercetin and chlorogenic acid (5-CQA). These concentrations in the fruits were, in order, 5-CQA, 4-MeO-5-CQA, Cy-3-sam, quercetin and Cy-3-glc, and their total content was equal to 42.4% of total polyphenols. By the ESR method, the superoxide anion radical scavenging activity was in the following order: Cy-3-sam, 4-MeO-5-CQA, Cy-3-glc, 5-CQA, quercetin; and the activity on hydroxyl radicals was in the order of Cy-3-sam, 5-CQA, quercetin, 4-MeO-5-CQA, Cy-3-glc. Cy-3-sam had the most potent antiradical activity, since the activities of Cy-3-sam were similar or higher than those of ascorbic acid. Our results suggest that these phenolic compounds, especially Cy-3-sam and chlorogenic acids may contribute to the antiradical activity and physiological effects of V. dilatatum fruits.

Protective effects of erdosteine on rotenone-induced oxidant injury in liver tissue

Rotenone, an insecticide of botanical origin, causes toxicity through inhibition of complex I of the respiratory chain in mitochondria. This study was undertaken to determine whether rotenone-induced liver oxidant injury is prevented by erdosteine, a mucolytic agent showing antioxidant properties. There were four groups of Male Wistar Albino rats: group one was untreated as control; the other groups were treated with erdosteine (50 mg/kg per day, orally), rotenone (2.5 mg/mL once and 1 mL/kg per day for 60 days, i.p.) or rotenone plus erdosteine, respectively. Rotenone treatment without erdosteine increased xanthine oxidase (XO) enzyme activity and also increased lipid peroxidation in liver tissue (P < 0.05). The rats treated with rotenone plus erdosteine produced a significant decrease in lipid peroxidation and XO activities in comparison with rotenone group (P < 0.05). Erdosteine treatment with rotenone led to an increase in catalase (CAT) and superoxide dismutase (SOD) activities in comparison with the rotenone group (P < 0.05). There was no significant difference in nitric oxide (NO) level between groups. There were negative correlations between CAT activity and malondialdehyde (MDA) level (r = -0.934, P < 0.05) with between CAT and SOD activities (r = -0.714, P < 0.05), and a positive correlation between SOD activity and MDA level (r = 0.828, P < 0.05) in rotenone group. In the rotenone plus erdosteine group, there was a negative correlation between XO activity and NO level in liver tissue (r = -0.833, P < 0.05). In the light of these findings, erdosteine may be a protective agent for rotenone-induced liver oxidative injury in rats.

Identification and antiradical properties of anthocyanins in fruits of Viburnum dilatatum thunb.

The fruit of Viburnum dilatatum Thunb., called gamazumi, has been shown to prevent oxidative injury in rats given gamazumi crude extract (GCE). Therefore, phenolic compounds in GCE were purified by Sephadex LH-20 column chromatography and preparative high-performance liquid chromatography. Two major anthocyanins were isolated, and their structures were determined by NMR, liquid chromatography/electrospray ionization mass spectrometry/MS and sugar analysis as cyanidin 3-O-(2-O-beta-D-xylopyranosyl)-beta-D-glucopyranoside, namely, cyanidin 3-sambubioside (I) and that of cyanidin 3-O-beta-D-glucopyranoside, namely, kuromanin (II). This is the first identification of these compounds in V. dilatatum fruits, which contain I and II at 141.3 and 4.5 microg/g of fresh fruit, respectively. By the electron spin resonance method, the superoxide anion radical scavenging activities (IC(50)) of I and II were 17.3 and 69.6 microM, and their activities on hydroxyl radicals were 4.3 and 53.2 mM. As a positive control, the activities of ascorbic acid were 74.2 microM on superoxide anion radicals and 3.0 mM on hydroxyl radicals. Our results suggest that these anthocyanins having radical scavenging properties may be key compounds contributing to the antioxidant activity and physiological effects of V. dilatatum fruits.

Effects of caffeic acid phenethyl ester against doxorubicin‐induced neuronal oxidant injury

AbstractOxygen‐derived free radicals have been implicated in the pathogenesis of doxorubicin‐induced toxicities. The aim of this study was to investigate the effects of caffeic acid phenethyl ester (CAPE), an antioxidant agent, on doxorubicin‐induced neuronal oxidative injury in rats. The rats were treated with CAPE (10μmol/kg/day i.p.) or saline starting 2 days before a single dose of doxorubicin (20 mg/kg i.p.) or saline. Ten days after the first experiments, the brain was excised to analyze the activities of antioxidant enzymes and levels of malondialdehyde (MDA) and nitric oxide (NO). Doxorubicin alone resulted in higher MDA level in brain tissue than the other groups. The activity of catalase was higher in doxorubicin plus CAPE group than doxorubicin group. There were no significant differences in NO level, glutathione peroxidase (GSH‐Px) and superoxide dismutase activities between the groups. There were negative correlations between GSG‐Px activity and MDA level in both doxorubicin and doxorubicin plus CAPE groups. It can be concluded that doxorubicin induced oxidant injury can be prevented by CAPE treatment through its antioxidant properties in rat brain.

Prevention of oxidative injury in PC12 cells by a traditional Chinese medicine, Shengmai San, as a model of an antioxidant-based composite formula.

The protective effect of Shengmai San (SMS) on oxidative damage in cultured PC12 cells was studied as a model of an antioxidant-based composite formula usable for the treatment of oxidative stress-related complex disorders. SMS, a traditional Chinese herbal medicine, has previously been shown to prevent cerebral oxidative injury in rats. Neuronal model PC12 cells were incubated with SMS for defined periods, chased with H(2)O(2) for 30 min at 37 degrees C, and subjected to an ELISA-based assay for determining the protein carbonyl content, and a Comet assay for DNA single strand breaks (SSBs). The results showed that both protein carbonyl content and DNA SSBs increased in PC12 cells after the H(2)O(2) chase in a concentration-dependent manner. Both H(2)O(2)-dependent carbonyl formation and DNA damage were markedly prevented in the cells pretreated with SMS, and the SMS effects were dependent on both the SMS concentration and the period of pre-incubation with SMS before the H(2)O(2) abuse. At the same time, cell viability was enhanced in the SMS-pretreated cells after the H(2)O(2) abuse compared to the control cells as determined by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It is concluded that SMS functions not only as a simple antioxidant but also as a modulator of cellular antioxidant defense.

Antioxidant potential of qizhu tang, a chinese herbal medicine, and the effect on cerebral oxidative damage after ischemia reperfusion in rats.

A traditional Chinese herbal medicine, Qizhu Tang (QZT) was studied for its in vitro antioxidant activity and the effect on cerebral oxidative damage after forebrain ischemia followed by reperfusion in rats. The QZT decoction was shown to have strong hydroxyl radical (*OH) scavenging activity (approx. 0.1 mM as Trolox equivalent) when determined by ESR using DMPO as a spin trap reagent and H2O2/UV as the *OH source. When the QZT decoction was injected into rat duodenum 2 h before cerebral ischemia, the oxidative brain damage after 45 min reperfusion was strongly inhibited in terms of two biochemical indications, thiobarbituric acid reactive substance formation and the loss of glutathione peroxidase. Since the QZT formula consists of 4 herbal constituents (Rhizoma atractylodis, Poria, Radix notoginseng and Radix astragali), each of the component herbs and their combinations were also examined for their protective effects on the cerebral ischemia/reperfusion injury and the effects were compared with their in vitro antioxidant potential. Although some of the incomplete formulas showed as strong antioxidant activities as complete QZT in vitro, only the complete QZT formula was effective in preventing cerebral oxidative injury in rats, and other preparations showed limited activity in vivo.