Effect of poly ICLC treatment on hepatic oxidative stress and antioxidant defense indices in Plasmodium yoelii nigeriensis infected mice

BACKGROUND: Plasmodium yoelii nigeriensis (P. y. nigeriensis) produces lethal malaria infection in Swiss albino mice. Reactive oxygen species (ROS) are important mediators of tissue injury during malaria infection. OBJECTIVE: To study the status of hepatic oxidative stress and antioxidant defense indices during Plasmodium yoelii nigeriensis (P. y. nigeriensis) infection and poly ICLC treatment of normal and P. y. nigeriensis infected Swiss albino mice. METHODS: Mice were divided into four groups viz., 1. Normal mice, 2. Normal mice treated with poly ICLC (5 mg/kg body weight, i.p.), 3. P. y. nigeriensis infected mice and 4. P. y. nigeriensis infected mice treated with poly ICLC (5 mg/kg body weight, i.p.). RESULTS: P. y. nigeriensis infection caused a significant increase in hepatic oxidative stress indices viz., xanthine oxidase and lipid peroxidation. This was accompanied by a significant increase in antioxidant defense indices viz., reduced glutathione (GSH), glutathione reductase while superoxide dismutase and catalase showed a significant decrease with respect to normal mice. Poly ICLC treatment of P. y. nigeriensis infected mice did not cure blood parasitemia. However, poly ICLC treatment of normal and P. y. nigeriensis resulted in an increased generation of hepatic oxidative stress and an associated increase in the antioxidant defense indices. CONCLUSION: poly ICLC therapy alone is not sufficient to treat the malaria infection caused by multiple drug resistant strain of P. y. nigeriensis. Therefore there is a need to develop newer antimalarias which can act alone or in combination with traditional antimalarials to be effective against drug resistant malarial parasite.     

Status of hepatic oxidative stress and antioxidant defense systems during chloroquine treatment of Plasmodium yoelii nigeriensis infected mice

BACKGROUND: Plasmodium yoelii nigeriensis (P. y. nigeriensis) produces lethal malaria infection in Swiss albino mice. Reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide have been implicated in the pathogenesis of malaria. OBJECTIVE: Study the effect of the chloroquine treatment on hepatic oxidative stress and antioxidant defense indices in multiple drug resistant (MDR) P. y. nigeriensis infected mice. METHODS: Mice were divided into four groups. Normal group, chloroquine treated normal group, P. y. nigeriensis infected group, and P. y. nigeriensis infected mice treated with chloroquine group (10 mg/kg body weight, i.p.). RESULTS: P. y. nigeriensis infection resulted in a significant decrease in the hepatic protein levels and caused a significant increase in the hepatic oxidative stress indices such as xanthine oxidase and lipid peroxidation and also an increase in the antioxidant defense indices viz, reduced glutathione (GSH), and glutathione reductase, but a significant decrease in superoxide dismutase (SOD) and catalase. The chloroquine treatment of P. y. nigeriensis (MDR strain) infected mice did not completely cure blood parasitemia, but resulted in a decrease of blood parasitemia. This was accompanied by decrease in hepatic oxidative stress indices and an associated change in the antioxidant defense indices towards normalization. CONCLUSION: Chloroquine therapy alone is not sufficient to treat the malaria infection caused by multiple drug resistant strain of P. y. nigeriensis. Therefore, there is a need to develop newer antimalarials which could act alone or in combination with traditional antimalarials to be effective against drug resistant malarial parasites.     

Antagonist effect of chloroquine and tumor necrosis factor on hepatic oxidative stress and antioxidant defense in normal and Plasmodium yoelii nigeriensis-infected mice

BACKGROUND: Plasmodium yoelii nigeriensis (P. y. nigeriensis) produces lethal malaria infection in Swiss albino mice. Tumor necrosis factor (TNF) has been implicated in the pathogenesis of malaria by production of reactive oxygen species. Chloroquine is a traditionally used antimalarial and has been postulated to inhibit TNF secretion during malaria infection. OBJECTIVE: The study the comparative effect of chloroquine and TNF treatment on hepatic oxidative stress and antioxidant defense indices in normal and P. y. nigeriensis-infected mice. MATERIALS AND METHODS: The mice were divided into six groups, each consisting of four to six animals. They were normal mice, normal mice treated with chloroquine, normal mice treated with TNF-alpha, P. y. nigeriensis-infected mice, P. y. nigeriensis-infected mice treated with chloroquine and P. y. nigeriensis-infected mice treated with TNF-alpha. RESULTS: Chloroquine treatment of the normal mice caused no significant alterations in hepatic oxidative stress and antioxidant defense indices while TNF treatment of normal mice caused a significant decrease in hepatic superoxide dismutase. Chloroquine treatment of P. y. nigeriensis-infected mice caused a decrease in blood parasitemia which was accompanied by restoration of altered indices to near normal levels. However, TNF treatment of P. y. nigeriensis-infected mice had no effect on blood parasitemia but caused a significant increase of hepatic xanthine oxidase and lipid peroxidation and a decrease in the activity of hepatic superoxide dismutase. CONCLUSION: Exogenous TNF acts synergistically with P. y. nigeriensis infection to generate oxidative stress in the host and also causes an impairment of the antioxidant defense enzyme SOD, while chloroquine treatment reduces the severity of malaria infection by decreasing the blood parasitemia and also perhaps by inhibiting the TNF release.     

Effect of beta-arteether treatment on erythrocytic methemoglobin reductase system in Plasmodium yoelii nigeriensis infected mice

BACKGROUND: The methemoglobin reductase system plays a vital role in maintaining the equilibrium between hemoglobin (Hb) and methemoglobin (MetHb) in blood. Exposure of red blood cells to an oxidative stress (pathological/physiological) may cause impairment in this equilibrium. OBJECTIVE: The status of MetHb and the related reductase system was studied during Plasmodium yoelii nigeriensis (P. y. nigeriensis) infection and beta-arteether treatment in mice. METHODS: Mice were divided into four groups. Normal group, normal mice treated with beta-arteether, P. y. nigeriensis infected mice and P. y. nigeriensis infected mice treated with beta-arteether. RESULTS: The present investigation revealed a marked decrease in the activity of MetHb reductase, with concomitant rise in MetHb levels during P. y. nigeriensis infection in mice erythrocytes (P < 0.001) as compared to normal mice. However, the activities of the associated enzymes viz., lactate dehydrogenase, glucose 6-phosphate dehydrogenase and glutathione reductase were found to be increased with progressive rise in parasitemia. beta-Arteether treatment (12.5 mg/kg body weight) of infected mice (parasitemia 20-25%) from day 5 of post infection resulted in complete clearance of parasitemia on day 7 of post infection, which was accompanied by restoration of all the altered above mentioned indices to near normal levels as compared to infected mice (P < 0.001). CONCLUSION: These results suggest that there is a marked impairment of methemoglobin and methemoglobin reductase system during P. y. nigeriensis infection in mice. beta-Arteether treatment of infected mice resulted in complete clearance of parasitemia which also caused the restoration of methemoglobin and methemoglobin reductase system to near normal levels.     

Studies on erythrocytic methemoglobin reductase systems in Plasmodium yoelii nigeriensis infected mice

BACKGROUND: The methemoglobin reductase system plays a vital role in maintaining the equilibrium between hemoglobin and methemoglobin in blood. Exposure of red blood cells to oxidative stress (pathological/physiological) causes an impairment in this equilibrium. OBJECTIVE: To study the status of methemoglobin and the related reductase system during Plasmoidum yoelii nigeriensis (P. y. nigeriensis) infection in mice. METHOD: Mice were divided into two groups viz., normal mice and P. y. nigeriensis infected mice. Malaria infection was induced by intraperitoneal inoculation of 10(6) infected erythrocytes. RESULTS: The present investigation revealed significant decrease in the activity of methemoglobin reductase, with concomitant rise in methemoglobin content during P. y. nigeriensis infection in mice erythrocytes. This was accompanied with a significant increase in reduced glutathione and ascorbic acid levels. Also the activities of the associated enzymes viz., lactate dehydrogenase, glucose-6-Phosphate dehydrogenase and glutathione reductase were found to increase with progressive rise in parasitemia. CONCLUSION: P. y. nigeriensis infection in mice results in impairment of methemoglobin reductase in the host.     

大黄对实验性肝坏死中肿瘤坏死因子、白细胞介素-6及一氧化氮的影响

目的 :观察大黄对四氯化碳 (CCl4)所至大鼠肝坏死的保护作用。方法 :采用CCl4 诱导大鼠肝坏死 ,观察大黄对肝坏死后肝脏组织及血清中肝功能、肿瘤坏死因子 (TNF-α)、白细胞介素 -6(IL-6)及一氧化氮 (NO)的变化。结果 :大黄可明显改善肝细胞损伤 ,显著降低血清中TNF -α、IL-6、NO的浓度 ,与对照组对比差异有显著性 (P<0.05～<0.01)。结论 :大黄对CCl4 性肝坏死有保护作用 ,其作用可能与抑制TNF-α、IL-6、NO等介质释放有关     

Influence of chloroquine treatment and Plasmodium falciparum malaria infection on some enzymatic and non-enzymatic antioxidant defense indices in humans

BACKGROUND: It is known that malaria infection is accompanied by increased production of reactive oxygen species (ROS) and that malaria parasites are sensitive to oxidative damage. This has been proved by the efficacy of some antimalarial drugs that are known to act via generation of ROS when administered clinically or experimentally. OBJECTIVE: There is lack of information on the effect of chloroquine on the antioxidant defense systems of normal and malaria infected humans. Since chloroquine has remained the mainstay of therapeutic regimen in malaria endemic zones, the present investigation was therefore undertaken to study the status of blood antioxidant defense mechanism, and oxidative stress following chloroquine treatment in normal and plasmodium infected humans. METHODS: Ten healthy persons (5 males and 5 females) with the same age range (18-35 years) were taken as control group. Ten other individuals were treated with 25 mg/kg body with chloroquine over three days. Ten patients with malaria, not under antimalarial therapy were taken as another group, while another set of 10 patients with malaria were treated with 25 mg/kg body weight over three days. RESULTS: The activity of superoxide dismutase was increased by 23% in individuals treated with chloroquine compared to controls while the activity of the enzyme decreased by 26% in malaria patients and by 43% in malaria patients treated with chloroquine. In all the treatment groups, the activities of catalase and glutathione peroxidase were lowered (P < 0.001). Similarly the levels of vitamins A, C, and beta-carotene were decreased in the treatment groups while plasma ceruloplasmin was increased in the groups. Glutathione and cholesterol levels were decreased while malondialdehyde level was increased significantly. CONCLUSION: Chloroquine treatment mediated oxidative stress in the host and this effect was exacerbated in Plasmodium falciparum infected patients administered with the drug.     

Enhancement of antioxidant defense mechanism by pitavastatin and rosuvastatin on obesity-induced oxidative stress in Wistar rats

Context: There has been a steady increase in the epidemiology of obesity over the last 30 years with developed countries leading the way. Oxidative stress was believed to be the principle contributor to the development of cardiovascular disorders that linked with obesity.

Objective: To evaluate the enhancement of antioxidant defense mechanism by Pitavastatin (PTV) and Rosuvastatin (RSV) on obesity-induced oxidative stress in Wistar rats.

Methods: Fifty Wistar albino rats were divided into five groups. High fat diet (HFD, 20?g/day/rat) pellets were given for 28 days to produce obesity-induced oxidative stress in Wistar rats. Oral administration of HFD along with PTV, RSV and Orlistat [(HFD for 28 days + from 8th day PTV (1?mg/kg), RSV (5?mg/kg) and Orlistat (10?mg/kg) to 28th day] were given respectively.

Results: Both PTV and RSV produced significant (p?<?0.01) reduction in serum apolipoprotein-B (Apo-B), total cholesterol (TC), triglycerides (TGs), cardiac-lipid peroxides (TBARS) levels and elevation in serum high density lipoprotein (HDL-C), cardiac antioxidant enzymes [glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catase (CAT)] levels.

Discussion and conclusion: Results were comparable with Orlistat, a standard antiobesity drug and present initial evidence that Pitavastatin and Rosuvastatin are useful for the treatment of obesity by enhancing the antioxidant defense mechanism. However, the effects of PTV were more prominent than RSV. The present findings of Pitavastatin and Rosuvastatin raise the possibility of a new application as an antiobesity therapeutic modality.     

Effect of bisphenol A on blood glucose,lipid profile and oxidative stress indices in adult male mice

Abstract

Bisphenol A (BPA), an endocrine-disrupting chemical, has been considered as a possible risk factor for diabetes and its complications. However, the underlying mechanisms of BPA-induced diabetes are not clear. The present study was performed to evaluate the effects of BPA on the hyperglycemia, lipid abnormalities and oxidative stress. In this study, the mice were divided into three groups of six animals each: One group as a control (C) and two other groups which exposed to 0.5 and 2?mg/kg concentrations of BPA. BPA powder was dissolved in sterile extra virgin olive oil and injected intraperitoneally to the tested groups, while the control group only received pure olive oil for 4 weeks. After 4 weeks, the changes of glucose, lipid profile reduced, total protein, glutathione (GSH), malondialdehyde (MDA), total antioxidant status (TAS), catalase (CAT) and super oxide dismutase (SOD) were determined in serum and pancreas. The results indicated that BPA dose-dependently increased the levels of blood glucose, lipid profile and MDA in the tested groups compared with the control group (p?<?0.001). BPA reduced significantly the levels of HDL-C and GSH in dose-dependent manner (p?<?0.001). BPA injection increased the levels of MDA and decreased the levels of GSH and TAS, and also the activities of SOD and CAT in the pancreas of exposed mice compared with the control group (p?<?0.05). In addition, body weight increased in the mice exposed to BPA compare to control animals. These results suggest that BPA exposure might induce hyperglycemia and its complications in adult male mice by induction of oxidative stress.     

Oxidized casein impairs antioxidant defense system and induces hepatic and renal injury in mice

ScopeOxidized protein products (OPPs) can be easily found in meat and milk during processing and storage. Evidence supports that accumulation of endogenous OPPs plays a negative role in physiological metabolism. However, the impacts of dietary OPPs and the mechanisms have not been elucidated yet. The present study evaluated whether oral oxidized casein would destruct the antioxidant defense system and cause potential oxidized injury in mice liver and kidney.Methods and resultsWe performed oxidized casein (modified respectively by H₂O₂–Cu and HClO) feeding experiments using KM mice (20–22 g). A 10-weeks feeding of oxidized casein as basal protein caused oxidative stress by increasing protein carbonylation (PC), advanced oxidation protein products (AOPPs), dityrosine (Dityr), lipid peroxidation and ROS levels in mice liver, kidney and blood (P < 0.05). In mice liver and kidney, the mRNA expression of Nrf2, γ-GCS, HO-1, GPX-3, and GPX-4 up-regulated, the protein level of Nrf2 in nucleus increased. However, activities of anti-oxidant enzymes (CAT, SOD, and GPX) decreased (P < 0.05). Moreover, histopathological examination displayed the formation of fibrous septa in mice liver and kidney after oxidized casein feeding.ConclusionOxidized casein impairs antioxidant defense system and induces hepatic and renal fibrosis.     

Interaction of pyridostigmine and physical stress on antioxidant defense system in skeletal muscle of mice

Pyridostigmine bromide (PB), a reversible anticholinesterase drug, had been used against possible nerve gas exposure during the Persian Gulf War. The Gulf War veterans used PB and they were under physical stress. This study investigated the delayed and interactive effects of pyridostigmine and physical stress on the antioxidant defense system in triceps muscle of mice. Male NIH Swiss mice were divided into four groups and treated as follows: sedentary control; pyridostigmine (1.2 mg kg(-1) p.o.); exercise; and PB plus exercise. Mice were exercised for 10 weeks, but PB was administered daily during the 5th and 6th weeks. Mice were sacrificed 24 h after the last treatments and the triceps muscle was isolated and analyzed. There was a significant increase in total superoxide dismutase (CuZn-SOD + Mn-SOD) activity (141% of control) with PB plus exercise, suggesting that any influx of superoxide anions was scavenged efficiently. The Mn-SOD enzyme protein levels were reduced significantly (63% of control) by PB plus exercise. Catalase enzyme protein levels were increased significantly by exercise (132% of control) as well as by PB plus exercise (139% of control). Glutathione levels were increased significantly by exercise alone (123% of control). Pyridostigmine bromide plus exercise significantly increased the malondialdehyde concentration (124% of control) in the triceps muscle, indicating an oxidative stress response of the combination. The data indicate that a combination of PB ingestion and exercise training significantly altered the antioxidant enzyme activities, enzyme protein levels and lipid peroxidation, leading to oxidative injury. Physical stress amplified the delayed effects of PB in the skeletal muscle of mice.     

Effects of ozone oxidative preconditioning on different hepatic biomarkers of oxidative stress in endotoxic shock in mice

In endotoxic shock, variations are known to occur in different biochemical parameters of oxidative stress. Ozone oxidative preconditioning (OOP) is a good candidate to restore the redox balance on different tissue. This investigation examined the effect of OOP on different biomarkers of oxidative stress in hepatic tissue of mice treated with lipopolysaccharide (LPS). LPS doses of 30?mg/kg were administered intraperitoneally (i.p.) and pretreatment with ozone/oxygen mixture (OOM) was applied i.p. at 0.2, 0.4, and 1.2?mg/kg once daily during 5 days before LPS injection. The mice were euthanized under ether atmosphere at different times, 1 and 24?h after LPS injection. Hepatic tissue from all animals was taken for biochemical determinations of oxidative stress parameters such as thiobarbituric acid reactive substances (TBARS) content and activity of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST). The results demonstrated that OOP reduces levels of TBARS content and increases the activity of GPx in hepatic tissue. In conclusion, OOP was able to recover the redox balance and in this way to protect the animals against the oxidative damage induced by endotoxemia.     

Effects of ozone oxidative preconditioning on different hepatic biomarkers of oxidative stress in endotoxic shock in mice

In endotoxic shock, variations are known to occur in different biochemical parameters of oxidative stress. Ozone oxidative preconditioning (OOP) is a good candidate to restore the redox balance on different tissue. This investigation examined the effect of OOP on different biomarkers of oxidative stress in hepatic tissue of mice treated with lipopolysaccharide (LPS). LPS doses of 30?mg/kg were administered intraperitoneally (i.p.) and pretreatment with ozone/oxygen mixture (OOM) was applied i.p. at 0.2, 0.4, and 1.2?mg/kg once daily during 5 days before LPS injection. The mice were euthanized under ether atmosphere at different times, 1 and 24?h after LPS injection. Hepatic tissue from all animals was taken for biochemical determinations of oxidative stress parameters such as thiobarbituric acid reactive substances (TBARS) content and activity of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST). The results demonstrated that OOP reduces levels of TBARS content and increases the activity of GPx in hepatic tissue. In conclusion, OOP was able to recover the redox balance and in this way to protect the animals against the oxidative damage induced by endotoxemia.     

Effect of fibrin glue on antioxidant defense mechanism,oxidative DNA damage and chromosomal aberrations

Abstract

Oxidative stress is involved in diverse biological phenomenon, and is caused by the imbalance between reactive oxygen species (ROS) and antioxidant defense system. 8-Hydroxy-2′-deoxyguanosine (8-OHdG) is the most critical biomarker in the estimation of ROS-induced DNA damage. This investigation focuses on the effect of fibrin glue on lipid peroxidation (LPO), antioxidant enzymes and oxidative DNA damage (both in vitro and in vivo). The blood biochemical parameters of the implanted animals and in vitro chromosomal aberrations were also studied. Fibrin glue was applied on the calvarial defect made on the anesthetized rats for an observation period of 4, 12, 26 and 52 weeks. At the end of the observation period, animals were anesthetized; blood was collected for serum analysis and was sacrificed. Brain was collected for the detection of 8-OHdG using competitive ELISA and liver was collected for analyzing the antioxidant enzymes and LPO. The results of this study suggest that the effect of fibrin glue on rat brain (in vivo and in vitro) and mice liver (in vitro) did not make any significant influence on LPO and antioxidant defense system. Similarly, there was no change observed in the expression of 8-OHdG. Serum constituents of implanted rats were observed to be within the normal range. The normal karyotype obtained indicates that the physiological saline extract of fibrin glue does not induce any chromosomal anomalies. Hence, it was concluded that the fibrin glue material does not have any potential to produce oxidative stress, alterations in the C-8 position of guanine and chromosomal anomalies.     

Nerium indicum leaf alleviates iron-induced oxidative stress and hepatic injury in mice

Abstract

Context: Nerium indicum Mill. (Apocynaceae) was reported for its efficient in vitro antioxidant and iron-chelating properties.

Objective: This study demonstrates the effect of 70% methanol extract of N. indicum leaf (NIME) towards in vitro DNA protection and ameliorating iron-overload-induced liver damage in mice.

Materials and methods: Phytochemical and HPLC analyses were carried out to standardize the extract and the effect of Fe²⁺-mediated pUC18 DNA cessation was studied. Thirty-six Swiss Albino mice were divided into six groups of blank, negative control (iron overload only), and iron-overloaded mice receiving 50, 100, and 200?mg/kg b.w. doses of NIME and desirox (20?mg/kg b.w.). The biochemical markers of hepatic damage, various liver and serum parameters, and reductive release of ferritin iron were studied.

Results and discussion: The presence of different phytocomponents was revealed from phytochemical and HPLC analyses. A substantial supercoiled DNA protection, with [P]₅₀ of 70.33?±?0.32?µg, was observed. NIME (200?mg/kg b.w.) significantly normalized the levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin by 126.27, 125.25, 188.48, and 45.47%, respectively. NIME (200?mg/kg b.w.) was shown to alleviate the reduced levels of superoxide dismutase, catalase, glutathione-S-transferase, and non-enzymatic-reduced glutathione, by 48.95, 35.9, 35.42, and 13.22%, respectively. NIME also lowered raised levels of lipid peroxidation, protein carbonyl, hydroxyproline, and liver iron by 32.28, 64.58, 136.81, and 83.55%, respectively.

Conclusion: These findings suggest that the active substances present in NIME may be capable of lessening iron overload-induced toxicity, and possibly be a useful drug for iron-overloaded diseases.     

Beta-carotene reduces oxidative stress,improves glutathione metabolism and modifies antioxidant defense systems in lead-exposed workers

The aim of this study was to determine whether beta-carotene administration reduces oxidative stress and influences antioxidant, mainly glutathione-related, defense systems in workers chronically exposed to lead.     

Lindane-induced oxidative stress. I. Time course of changes in hepatic microsomal parameters, antioxidant enzymes, lipid peroxidative indices and morphological characteristics

1. Lindane (60 mg/kg) administered orally to rats increased liver cytochrome P-450 content and superoxide radical (O2-.) generation 24 h after treatment, while formation of thiobarbituric acid reactants and NADPH/ADP-supported microsomal chemiluminescence were significantly increased 4 h after treatment. 2. Hepatic superoxide dismutase (SOD) and catalase decreased 6 h after lindane treatment and SOD/O2-. ratio progressively decreased during 4 to 24 h after lindane treatment. 3. Morphological evidence of hepatic cell injury after lindane treatment was seen at all times studied, and appeared to increase with time. 4. Lindane administration results in time-dependent oxidative stress in liver which involves an early component (4-6 h) related to the reductive metabolism of lindane, and a late component (24 h) associated with the induction of cytochrome P-450; the biochemical changes correlated with the observed morphological lesions.     

重组修饰人肿瘤坏死因子突变体在小鼠体内的药代动力学(英文)

采用酶联免疫吸附测定法 ,检测血浆中新型重组人肿瘤坏死因子 (rhTNF NC)的含量 ,研究rhTNF NC在小鼠体内的药代动力学 .rhTNF NCiv后 ,血药浓度时间曲线符合非线性药代动力学特征 ,t1/2 β平均为 37.4min ,3个剂量的AUC分别为 4 .0 8,10 .3和57.3mg·min·L- 1,而Cls则分别为 0 .38,0 .18和0 .0 7mL·min- 1.