Compromised antioxidant status and persistent oxidative stress in lung transplant recipients.

Oxidative stress may be a key feature, and hence important determinant, of tissue injury and allograft rejection in lung transplant recipients. To investigate this, we determined the antioxidant status (urate, ascorbate, thiols and alpha-tocopherol) and lipid peroxidation status (malondialdehyde) in bronchoalveolar lavage (BAL) fluid and blood serum of 19 consecutive lung transplant recipients 2 weeks and 1, 2, 3, 6, and 12 months post-surgery. BAL fluid and blood samples from 23 control subjects and blood from 8 patients two days before transplantation were obtained for comparison. Before surgery, the antioxidant status of patients was poor as serum ascorbate and total thiol concentrations were significantly (p < 0.05) lower than control subjects. Two weeks post-surgery, ascorbate and total thiol concentrations were still low and urate concentrations had fallen compared to control subjects (p < 0.01). At this time, BAL fluid urate concentration was higher (p < 0.01), ascorbate concentration was lower (p < 0.01) and reduced glutathione concentrations were similar to control subjects. MDA, a product of lipid peroxidation, was higher (p < 0.01) in both BAL fluid and serum obtained from transplant patients compared to control subjects. During the first 12 months post-surgery, little improvement in antioxidant status or extent of lipid peroxidation was seen in transplant recipients. Regression analysis indicated no difference in serum or BAL fluid antioxidant status in patients with acute rejection compared to those without. In conclusion, lung transplant recipients have a compromised antioxidant status before surgery and it remains poor for at least the first year following the operation. In addition, these patients have elevated MDA concentrations in both their lung lining fluid and blood over most of this time. Oxidative stress is not, however, a sufficiently sensitive endpoint to predict tissue rejection in this group.     

Local and systemic oxidant/antioxidant status before and during lung cancer radiotherapy

To examine local and systemic oxidative status of lung cancer (LC) and oxidant effects of radiotherapy (RT), this study evaluated antioxidants and markers of oxidative and nitrosative stress in bronchoalveolar lavage (BAL) fluid and in the blood of 36 LC patients and 36 non-cancer controls at baseline and during and after RT for LC. LC patients had higher baseline serum urate, plasma nitrite and lower serum oxidized proteins than controls (p=0.016, p<0.001 and p=0.027, respectively), but BAL fluid oxidative stress markers were similar. RT tended to raise some antioxidants, however, significant increases were seen in serum urate, conjugated dienes and TBARS (p=0.044, p=0.034 and p=0.004, respectively) 3 months after RT. High urate at baseline may compensate against the oxidative stress caused by LC. RT shifts the oxidant/antioxidant balance towards lipid peroxidation, although the antioxidant defense mechanisms of the body appear to counteract the increased oxidative stress rather effectively.     

Synthesis of ascorbate and urate in the ovary of water buffalo

Blood flow interruption is associated with oxygen depletion and loss of factors for function and survival in downstream tissues or cells. Hypoxia and absence of gonadotropins trigger apoptosis and atresia in the ovary. We studied the antioxidant response of follicular cells to plasma deprivation in ovaries dissected from water buffalo. Aliquots of follicular fluid were aspirated from each antral follicle, before and during incubation of the ovaries at 39°C. Urate, ascorbate, retinol and α-tocopherol in the fluid were, titrated by High Performance Liquid Chromatography (HPLC) with spectrophotometric or spectrofluorimetric detection. The total antioxidant capacity of follicular fluid was determined as absorbance decrease, following addition of a source of radical chromophores. The more the incubation progressed, the higher levels of urate, ascorbate and total antioxidant capacity were found. Conversely, changes in concentration of the liposoluble antioxidants were not observed. Ascorbate synthesizing activity in the follicle was demonstrated by detecting the enzyme L-gulono-γ-lactone oxidase in microsomes prepared from granulosa cells. These cells were also analyzed for the expression of the enzyme CPP32. The enzyme level, measured as DEVD-p-nitroanilide cleaving activity, was found related with the immunoreactivity to anti-CPP32 antibodies. Negative correlation between the enzyme activity (which is known to be induced by peroxynitrite) and the follicular level of urate (which scavenges peroxynitrite) was also observed. The amount of nitrotyrosine, a product of peroxynitrite attack on proteins, was measured in follicular fluids by Enzyme Linked ImmunoSorbent Assay (ELISA). This amount was found positively correlated with the CPP32 activity, and negatively correlated with the urate level in follicular fluid. Alterations in concentrations of ascorbate or urate may be associated with oxidative stress during follicular atresia.     

Antioxidant status and lipid peroxidation in hemodialysis patients undergoing erythropoietin and erythropoietin-vitamin E combined therapy

In this study, plasma and red blood cell (RBC) antioxidant status and plasma lipid peroxidation were investigated in 46 hemodialysis patients. In addition, the effect of erythropoietin (EPO) and EPO-vitamin E combination therapy on plasma and RBC antioxidant status, and plasma lipid peroxidation were examined.

There were 10 healthy subjects in the control group and 10 hemodialysis patients in the untreated group. The third group included 36 hemodialysis patients that were given EPO (100 U/kg) for 3 months, 3 times per week. The fourth group included 36 hemodialysis-patients from the EPO group that were given EPO at a 50% decreased dose + vitamin E (300 mg/day) for 3 months.

MDA levels in the untreated group, the EPO group and the EPO + vitamin E groups were found to be higher than the control group (p<0.001, in both). Furthermore, MDA levels in both of the treatment groups were lower when compared to the untreated group (p<0.001, in both). Plasma vitamin E levels in the untreated, the EPO group and EPO + vitamin E groups were lower than the control group (p<0.001). In contrast, plasma vitamin E levels in the treatment groups were higher in comparison with the control group (p<0.05). SOD activities in the untreated, the EPO group and the EPO + vitamin E groups were found to be lower than the control group (p<0.001). SOD activities in the treatment groups were higher than the control group (p<0.001). The SOD activities in the EPO + vitamin E group increased when compared to the EPO group (p<0.001). CAT activities in the untreated, the EPO group and the EPO + vitamin E groups were found to be lower than the control group (p<0.001 in untreated and EPO groups, p<0.01 in EPO + vitamin E group). CAT activities in EPO and EPO + vitamin E groups were increased when compared to the untreated group (p<0.01).

In conclusion, our findings have shown that antioxidant status decreased and lipid peroxidation increased in hemodialysis patients. EPO has an antioxidant effect on the RBC and plasma antioxidant status, and plasma lipid peroxidation. These effects were moderately increased by the combination of vitamin E and EPO.     

Alterations in plasma essential trace elements selenium, manganese, zinc, copper, and iron concentrations and the possible role of these elements on oxidative status in patients with childhood asthma

The aim of the present study is to evaluate the status of plasma essential trace element selenium (Se), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) concentrations and the effect of these elements on oxidative status in patients with childhood asthma. Plasma Se, Mn, Cu, and Zn concentrations were determined by atomic absorption spectrophotometry (AAS) and Fe concentrations, malondialdehyde (MDA), and total antioxidant capacity (TAC) were determined by the colorimetric method. The plasma MDA/TAC ratio was calculated as an index of oxidative status. Plasma albumin levels were measured to determine nutritional status. Plasma Fe concentrations, MDA levels and the MDA/TAC ratio were significantly higher (p<0.001, p<0.001, and p<0.01, respectively) and Se and Mn concentrations and TAC were lower (p<0.01, p<0.05, and p<0.01, respectively) in patients when compared to the healthy subjects. Plasma Zn, Cu, and albumin levels were not found to be significantly different in patients and controls (p>0.05). There were positive relationships between plasma MDA and Fe (r=0.545, p<0.001) and TAC and Se (r=0.485, p<0.021), and a negative correlation between TAC and MDA values (r= −0.337, p<0.031) in patients with childhood asthma. However, there was no correlation between these trace elements and albumin content in patient groups. These observations suggest that increased Fe and decreased Se concentrations in patients with childhood asthma may be responsible for the oxidant/antioxidant imbalance.     

Evaluation of Oxidative Stress, Antioxidant Status and Serum Vitamin C Levels in Cancer Patients

Taking into account the importance role of lipid peroxidation and antioxidants in the prevention and incidence of cancer, the present study was carried out to determine oxidative stress, serum total antioxidant (TAS), and vitamin C levels in cancer patients. Malondialdehyde(MDA), total antioxidant status, and vitamin C levels of 57cancer patients aged 19–80 years and 22 healthy subjects (control group) aged 22–76 years were evaluated. Serum concentrations of MDA as thiobarbitaric acid complexes were measured by fluorometry method, the serum TAS by using commercial test kits from Randox Laboratories, and vitamin C by using spectrocolorimetric method. The mean serum MDA concentrations of all cancer groups except lung cancer were significantly higher than control group (P < 0.004). The mean total antioxidant status was insignificantly higher than control group. The mean serum vitamin C level was significantly lower in patients as compared to the healthy subjects (PV < 0.0001). In conclusion, an alteration in the lipid peroxidation with concomitant changes in antioxidant defense system in cancer patients may be due to excessive oxidative stress. Serum low levels of vitamin C in the different type of cancer patients in spite of adequate daily intake may be due to increased utilization to scavenge lipid peroxides as well as their sequestration by tumor cells.     

Breath Condensate Hydrogen Peroxide Correlates with Both Airway Cytology and Epithelial Lining Fluid Ascorbic Acid Concentration in the Horse

The relationship between hydrogen peroxide (H²O²) concentration in expired breath condensate (EBC) and cytology of the respiratory tract obtained from tracheal wash (TW) or bronchoalveolar lavage (BAL), and epithelial lining fluid (ELF) antioxidant status is unknown. To examine this we analysed the concentration of H²O² in breath condensate from healthy horses and horses affected by recurrent airway obstruction (RAO), a condition considered to be an animal model of human asthma. The degree of airway inflammation was determined by assessing TW inflammation as mucus, cell density and neutrophil scores, and by BAL cytology. ELF antioxidant status was determined by measurement of ascorbic acid, dehydroascorbate, reduced and oxidised glutathione, uric acid and α-tocopherol concentrations. RAO-affected horses with marked airway inflammation had significantly higher concentrations of breath condensate H²O² than control horses and RAO-affected horses in the absence of inflammation (2.0±0.5?μmol/l, 0.4±0.2?μmol/l and 0.9±0.2?μmol/l H²O², respectively; p<0.0001). The concentration of breath condensate H²O² was related inversely to the concentration of ascorbic acid in ELF (r=-0.80; p<0.0001) and correlated positively with TW inflammation score (r=0.76, p<0.0001) and BAL neutrophil count (r=0.80, p<0.0001). We conclude that the concentration of H²O² in breath condensate influences the ELF ascorbic acid concentration and provides a non-invasive diagnostic indicator of the severity of neutrophilic airway inflammation.     

Antioxidant properties of chromium and zinc

The effects of chromium (chromium picolinate, CrPic) and zinc (ZnSO₄H₂O) supplementation on serum concentrations of malondialdehyde (MDA) (an indicator of lipid peroxidation) and serum status of some antioxidant vitamins and minerals of laying hens (Hy-Line) reared at a low ambient temperature (6.8°C) were evaluated. One hundred twenty laying hens (Hy-Line; 32 wk old) were divided into 4 groups, 30 hens per group. The hens were fed either a basal diet or the basal diet supplemented with either 0.4 mg Cr/kg of diet, 30 mg Zn/kg of diet, or 0.4 mg Cr plus 30 mg Zn/kg of diet. Digestibility of nutrients (dry matter [DM], organic matter [OM], crude protein [CP], and ether extract [EE]) increased by supplementation of chromium and zinc (p<0.05). Supplemental chromium and zinc increased serum vitamins C and E but decreased MDA concentrations (p<0.05). Additionally, supplemental chromium and zinc caused an increase in the serum concentrations of Fe, Zn, Mn, and Cr (p < 0.05). The present study showed that low ambient temperature causes detrimental effects on the digestibility of nutrients and antioxidant status and that such detrimental effects caused by low ambient temperature can be alleviated by chromium and zinc supplementation, particularly when Cr and Zn were simultaneously included into the diet. Data obtained in the present study suggest that such supplementation can be considered as a protective management practice in a diet of laying hens for alleviating negative effects of cold stress.     

Age-related changes in antioxidant enzyme activities, fatty acid composition and lipid peroxidation in whole body Gammarus locusta (Crustacea: Amphipoda)

The main aim of this work was to provide baseline data on aspects of pro-oxidant and antioxidant processes in different life-stages of the marine amphipod Gammarus locusta. The activities of antioxidant enzymes and levels of lipid peroxidation were determined in whole body juveniles, subadults, and male and female adults of a laboratory population of G. locusta. Fatty acid composition of individuals at these different stages of development was also characterised in order to examine the contribution that polyunsaturated fatty acids (PUFA) might make to the peroxidation status of animals. The antioxidant enzymes, measured in whole body 100,000 supernatants, comprised catalase (CAT, EC 1.11.1.6), superoxide dismutase (SOD; EC 1.15.1.1) and glutathione peroxidase (GPX; EC 1.11.1.9). Fatty acids were analysed as fatty acid methyl esters (FAME). Lipid peroxidation was examined in terms of the levels of lipid peroxides determined as thiobarbituric acid-reactive malondialdehyde equivalents. Age-related changes were seen in antioxidant enzyme status: levels of SOD (p<0.01) and GPX (p<0.001) activities decreased progressively during development from juveniles to adults. Sex-related changes in GPX activity were also seen, the levels being higher in adult males than females (p<0.001). The amount of FAME present in whole body amphipod also changed over the life span. Among PUFA, the eicosapentaenoic (C20:5n-3), arachidonic (C20:4n-6) and docosahexaenoic (C22:6n-3) were the most abundant acids in this species, and both their individual concentrations and total PUFA increased progressively with age (up to 3.3-fold; p<0.001). The latter changes may contribute to the explanation of the observed differences in peroxidation status of the animals with age; thus, levels of lipid peroxides increased up to 40% in adult males compared to other age-classes (p<0.01). Overall, the decline in antioxidant enzyme activities, coupled with increased levels of PUFA, as the individual grows older, may render the older animals more susceptible to lipid peroxidation and oxidative stress.     

Synovial fluid and plasma selenium, copper, zinc, and iron concentrations in patients with rheumatoid arthritis and osteoarthritis

In recent years, a great number of studies have investigated the possible role of trace elements in the etiology and pathogenesis of rheumatoid arthritis (RA) and osteoartritis (OA). We studied synovial fluid and plasma concentrations of selenium (Se), zinc (Zn), copper (Cu), and iron (Fe) in patients with RA and OA and compared them with sex- and age-matched healthy subjects. Plasma albumin levels were measured as an index of nutritional status. Plasma Se, Cu, and Zn concentrations were determined by atomic absorption spectrophotometry and Fe concentrations were determined by the colorimetric method. Although plasma and synovial fluid Se concentration were found to be significantly lower (p<0.05, and p<0.05, respectively), Cu concentrations were significantly higher in patients with RA than those of healthy subjects and OA (p<0.05 and p<0.05, respectively). There were no significant differences in plasma and synovial fluid Zn concentrations and albumin levels among three groups (p>0.05). On the other hand, synovial fluid Cu and Fe concentrations were significantly higher in patients with OA than those of healthy subjects (p<0.05). There was a significantly positive correlation between synovial fluid Se−Cu values and Zn−Fe values in patients with RA. Our results showed that synovial fluid and plasma trace element concentrations, excluding Zn, change in inflammatory RA, but not in OA. These alterations in trace element concentrations in inflammatory Ra might be a result on the changes of the immunoregulatory cytokines.     

Galactomannan detection in nonserum specimens: Where do we stand?

Aspergillus species have emerged as a cause of devastating infections in immunocompromised patients. A circulating antigen in aspergillosis is galactomannan (GM), a cell wall constituent released during growth. GM can be detected in serum of neutropenic patients at an early stage of disease, often before clinical signs become apparent. Until recently, data regarding performance of the test in other fluids were lacking. It was suggested that, in absence of neutropenia, viable fungi can endure in lung tissue, whereas circulating markers remained undetectable because of clearance by circulating neutrophils. Indeed, bronchoalveolar lavage (BAL) fluid proved to be a better specimen for the diagnosis of invasive aspergillosis in critically ill patients. The published clinical experience with GM in BAL fluid in solid organ transplant recipients also showed promising results. The evidence for using GM in other body fluids, such as cerebrospinal fluid and urine, is based on case reports. The objective of this review is to summarize the current evidence for GM detection in nonserum fluids.     

An in vitro and in vivo investigation of the effects of diesel exhaust on human airway lining fluid antioxidants

Breathing high concentrations of diesel exhaust (DE) induces pulmonary inflammation, bronchoconstriction, increased airway reactivity, and oxidative stress in healthy subjects. To examine if these responses occur at environmentally relevant concentrations of DE, we exposed 25 healthy subjects to DE (PM(10) 100 microg/m(3), 0.6 ppm NO(2) for 2-h) and filtered air on separate occasions. Immediately following DE exposure, subjects displayed an increase in subjective symptoms and a mild bronchoconstriction. Six hours following the cessation of DE exposure neither airway inflammation, nor antioxidant depletion (ascorbate, urate, and reduced glutathione), was seen at any level of the respiratory tract. Instead, an increased flux of reduced glutathione into the bronchial (p < 0.01) and nasal airways (p < 0.05) was observed. In separate, in vitro experiments, DE was found to have comparable oxidative activity to the transition metal rich residual oil fly ash (ROFA) particle, significantly depleting lung lining fluid ascorbic acid and reduced glutathione in a transition metal and superoxide-dependent mechanism. Together, these data indicate that even though DE has marked oxidative activity, this effect is not observed to any great extent in the airways of healthy subjects. We interpret these findings as being indicative that the antioxidant network at the air-lung interface in healthy subjects is capable of dealing with the oxidative challenge posed by DE at ambient concentrations.     

Quantification of Cytokeratin 5 mRNA Expression in the Circulation of Healthy Human Subjects and after Lung Transplantation

Background

Circulating epithelial progenitor cells are important for repair of the airway epithelium in a mouse model of tracheal transplantation. We therefore hypothesized that circulating epithelial progenitor cells would also be present in normal human subjects and could be important for repair of the airway after lung injury. As lung transplantation is associated with lung injury, which is severe early on and exacerbated during episodes of infection and rejection, we hypothesized that circulating epithelial progenitor cell levels could predict clinical outcome following lung transplantation.

Methodology/Principal Findings

Quantitative Real Time PCR was performed to determine peripheral blood mRNA levels of cytokeratin 5, a previously characterized marker of circulating epithelial progenitor cells. Cytokeratin 5 levels were evaluated in healthy human subjects, in lung transplant recipients immediately post-transplant and serially thereafter, and in heart transplant recipients. All normal human subjects examined expressed cytokeratin 5 in their buffy coat in amounts that were not significantly influenced by age or gender. There was a profound, statistically significant decrease in cytokeratin 5 mRNA expression levels in lung transplant patients compared to healthy human subjects (p = 3.1×10⁻¹³) and to heart transplant recipients. There was a moderate negative correlation between improved circulating cytokeratin 5 mRNA levels in lung transplant recipients with recovering lung function, as measured by improved FEV1 values (rho = −0.39).

Conclusions/Significance

Levels of cytokeratin 5 mRNA, a proxy marker for circulating epithelial progenitor cells, inversely correlated with disease status in lung transplant recipients. It may therefore serve as a biomarker of the clinical outcome of lung transplant patients and potentially other patients with airway injury.     

Anti-oxidant supplementation decreases TBA reactants in serum of elderly

An “anti-oxidant cocktail” consisting of betacarotene, vitamins B₆, C, E, zinc, and selenium or corresponding placebos were given for one y as daily dietary supplements to 45 elderly residents of a nursing home. Initially, the serum TBA reactant levels were higher (2.7±0.7 μmol/L) than those of an ad hoc control group of healthy younger adults (2.3±0.6 μmol/L),p<0.01. After three mo supplementation, the levels among the verum elderly had decreased to 2.2±0.6 μmol/L, and they remained at this lower level until the end of the study period, whereas the placebo group showed no change. A significant inverse correlation (r=−0.428,p<0.01) existed between the concentrations of serum TBA reactants and whole blood selenium (B-Se), but only B-Se levels above 200 μg/L were associated with a decrease in serum lipid peroxides. Serum alpha-tocopherol concentration also correlated inversely with serum TBA reactants but this correlation (r=−0.273,p<0.76) was not as strong as that of B-Se. Deficient vitamin B₆ status, in biochemical terms, was observed in 25% of the elderly; a daily supplement of 2 mg B₆ fully cured all cases of deficiency. The verum group improved slightly in several psychological tests, whereas subjects on placebo remained unchanged or deteriorated during the follow-up period. Clinical amelioration among the verum subjects was reported by the nurses; no toxic side effects were reported. In conclusion, the elderly benefited biochemically and clinically of dietary antioxidant supplements.     

Lipoperoxides as an index of free radical activity in bone marrow transplant recipients

It has been previously demonstrated that the conditioning therapy given to bone marrow transplant (BMT) recipients creates a high oxidant stress, resulting in a measured reduction in antioxidants, such as glutathione peroxidase (GSH-Px), vitamin E, and cell peroxide fragilities. As part of a current intervention trial of antioxidant therapy in BMT recipients, plasma thiobarbituric acid reactive substances (TBARS) were measured to assess peroxidation and free radical activity. Measurements were performed before and after conditioning therapy, and then at weekly intervals for a period of 6 wk after transplantation in 20 patients (10 controls and 10 antioxidant therapy [AOT] recipients). The TBARS results were compared with concurrent measurements of more specific elements of the antioxidant pathways, such as red blood cell glutathione peroxidase (RBC-GSH-Px), plasma vitamin C, and serum vitamin E. In all cases, TBARS concentration was significantly increased after conditioning compared with baseline levels (p<0.001), an increase that correlated inversely with RBC-GSH-Px (r=?0.81;p<0.01). The TBARS concentration fell gradually after conditioning in all patients. The fall in the AOT group was more rapid than in the control group, and it paralleled the gradual return toward normal levels of the other antioxidants. The change in TBARS concentration occurred faster than changes in other indices, suggesting that TBARS might be a better index of overall free radical activity. Although the patient numbers are small, there is some evidence to suggest that MDA may act as a prognostic marker. In 70% of the patients with a poor postoperative course and who eventually died, the peak TBARS concentration was significantly higher than that in the successful transplants. Also, the fall in TBARS concentration was much slower (if at all). This point requires further investigation and a more detailed analysis on a larger number of patients.     

Modulatory Effects of Shape Pluchea Lanceolata Against Chemically Induced Oxidative Damage, Hyperproliferation And Two-Stage Renal Carcinogenesis in Wistar Rats

Ferric nitrilotriacetate (Fe-NTA) is a well-established renal carcinogen. Here, we have shown that Pluchea lanceolata (PL) belonging to the family Asteraceae. PL attenuates Fe-NTA induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in rats. It promoted DEN (N-diethyl nitrosamine) initiated renal carcinogenesis by increasing the percentage incidence of tumors and induces early tumor markers viz. ornithine decarboxylase (ODC) and renal DNA synthesis. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) also enhances renal lipid peroxidation (LPO), xanthine oxidase (XO) and hydrogen peroxide (H₂O₂) generation with reduction in renal glutathione content (GSH), antioxidant enzymes, viz., glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), glucose-6-phosphate dehydrogenase and phase-II metabolizing enzymes such as glutathione-S-transferase and quinone reductase (QR). It also enhances blood urea nitrogen (BUN) and serum creatinine. Oral treatment of rats with PL extract (100 and 200 mg/kg body weight) resulted in significant decrease in lipid peroxidation (LPO), xanthine oxidase (XO), H₂O₂ generation, blood urea nitrogen (BUN), serum creatinine, renal ODC activity, DNA synthesis (p < 0.001) and incidence of tumors. Renal glutathione content (p < 0.01), its metabolizing enzymes (p < 0.001) and antioxidant enzymes were also recovered to significant level (p < 0.001). Thus, present study supports PL as a potent chemopreventive agent and suppresses Fe-NTA-induced renal carcinogenesis and oxidative damage response in Wistar rat.     

Effect of cadmium on lipid peroxidation and activities of antioxidant enzymes in growing pigs

Malondialdehyde (MDA), glutathione (GSH) content, total antioxidant capacity (T-AOC) levels, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione transferase (GST) activities were studied in serum, liver, and kidney of growing pigs after graded doses of cadmium administration in diets. One hundred ninety-two barrows (Duroc x Landrace x Yorkshire), with similar initial body weight 27.67±1.33 kg, were randomly allotted into 4 different treatments with 3 replications (16 pigs per replication). The treatments received the same basal diet added with 0, 0.5, 5.0, and 10.0 mg/kg cadmium (as CdCl₂), respectively. The results showed pigs treated with 10 mg/kg cadmium significantly decreased average daily gain (ADG) (p<0.05) and increased feed/gain ratio (F/G) (p<0.05) compared to the control. In this treatment, the contents of MDA increased significantly (p<0.05), GSH concentrations, T-AOC levels, and the activities of SOD, GSH-PX, and GST decreased significantly (p<0.05). The results indicate 10 mg/kg cadmium could decrease pig antioxidant capacity after extended exposure and cadmium-induced increase lipid peroxidation might not be only the result of the possibility of lower level of GSH but could also be as a result of direct action of cadmium on peroxidation reaction.     

Antioxidant enzyme activities and lipid peroxidation induced by eicosapentaenoic acid (EPA) in PC12 cells

Eicosapentaenoic acid (EPA) is one of the major dietary polyunsaturated fatty acids and induces apoptosis in several cancer cells. In this study, the EPA induced lipid peroxidation and response of antioxidative enzymes have been investigated in rat pheochromocytoma PC12 cells to elucidate the mechanisms of apoptosis induced by the polyunsaturated fatty acid EPA. We have analyzed superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities and glutathione (GSH) contents in PC12 cells after exposure to different concentrations of EPA. Lipid peroxidation was shown to increase in the presence of EPA as an indication of the oxidative damage. Lipid peroxidation was enhanced by EPA in a dose-dependent manner, and the loss of cell viability was partially reversed by vitamin E. In the case of antioxidant enzyme activities, SOD and GPX activities and GSH contents increased significantly at 50 μmol/L EPA and were respectively 2.41-fold (p < 0.01), 3.49-fold (p < 0.05), and 1.43-fold (p < 0.05) higher than controls. The CAT activity at 10 μmol/L had the highest value and was increased by 25.83% (p < 0.05) compared to control. The results suggest that in PC12 cells the mechanism of apoptosis induced by EPA may be partly due to lipid peroxidation.     

Mitigating role of lupeol and lupeol linoleate on hepatic lipemic-oxidative injury and lipoprotein peroxidation in experimental hypercholesterolemia

In the present study, the role of pentacyclic triterpenes, lupeol and its ester lupeol linoleate, was studied in relation to hepatic oxidative abnormalities and lipoprotein peroxidation in hypercholesterolemic rats. Hypercholesterolemia was induced in male Wistar rats by feeding them with high cholesterol diet (4% cholesterol + 1% cholic acid; HCD) for 30 days. Pentacyclic triterpenes, lupeol and lupeol linoleate were supplemented (50 mg/kg body wt/day) during the last 15 days. After the experimental period, there was a significant depression in hepatic activities of antioxidant enzymes, SOD (38.39%), CAT (25.03%) and GPx (30.26%) along with a marked fall in the levels of non-enzymic antioxidant molecules GSH (31.39%), vitamin C (46.07%) and vitamin E (42.28%), with a concomitant increase (p<0.001) in lipid peroxidation and in the activities of serum alkaline phosphatase, lactate dehydrogenase and aminotransferases when compared to controls. Treatment with triterpenes decreased lipid peroxidation and reverted the activities of antioxidants (p<0.001 and p<0.01) and marker enzymes to near control. Histopathological findings further confirmed the hepatoprotective nature of triterpenes by showing the normal architecture in treated rats, as against the fatty cellular changes in HCD fed rats. Further, the susceptibility of apo-B containing lipoprotein to oxidation by copper and Fenton’s reagent was increased in in vitro condition in HCD fed rats, whereas the lipoproteins were less susceptible to oxidation in triterpenes treated animals. Therefore, it may be concluded that lupeol and its ester afford protection against the hepatic abnormalities and lipoprotein peroxidation in hypercholesterolemic rats.     

Mitigation of oxidative stress in cyclophosphamide-challenged hepatic tissue by DL-α-lipoic acid

The present study investigated the protective effect of DL--lipoic acid on the tissue peroxidative damage and abnormal antioxidant levels in cyclophosphamide (CP) induced hepatotoxicity. Male Wistar rats of 140± 20 g were categorized into four groups. Two groups were administered CP (15 mg/kg body weight once a week for 10 weeks by oral gavage) to induce hepatotoxicity; one of these groups received lipoic acid treatment (35 mg/kg body weight intraperitoneally once a week for 10 weeks; 24 h prior to the CP administration). A vehicle (saline) treated control group and a lipoic acid drug control group were also included. The extent of liver damage in CP-induced rats was evident from the increased activities of serum aminotransferases, alkaline phosphatase and lactate dehydrogenase; whereas lipoic acid pretreatment prevented the rise in these marker enzymes. We evaluated the changes in activities/levels of tissue enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and glucose-6-phosphate dehydrogenase) and non-enzymic (reduced glutathione, ascorbate and -tocopherol) antioxidants along with malondialdehyde levels in the experimental groups. In CP-administered rats the antioxidant enzymes showed significantly depressed activities (p < 0.001, p < 0.01) and the antioxidant molecules also showed depleted levels (p < 0.001, p < 0.01), in comparison with the control group. However the extent of lipid peroxidation and the abnormal antioxidant status were normalized in lipoic acid pretreated rats. The present work highlights the efficacy of lipoic acid as a cytoprotectant in CP-induced hepatic oxidative injury.