Cell Antioxidant Enzyme Activities Research Articles

Anti-Inflammatory Activity of Peptides from Ruditapes philippinarum in Lipopolysaccharide-Induced RAW264.7 Cells and Mice.

In our previous study, two peptides with favorable anti-inflammatory effects, Asp-Gln-Thr-Phe (DQTF) and Gly-Tyr-Thr-Arg (GYTR), were screened from Ruditapes philippinarum using an in vitro-in silico strategy. The present study aims to investigate the ameliorative effect of Ruditapes philippinarum peptides (RPPs) on acute inflammation and clarify the potential mechanism through in vitro and in vivo experiments. The anti-inflammatory effects of DQTF and GYTR were verified with a lipopolysaccharide (LPS)-induced RAW264.7 cell acute inflammation model and the anti-inflammatory effect of the enzymatic hydrolysates of Ruditapes philippinarum was explored in vivo using an LPS-induced acute inflammatory injury model in mice. The results show that DQTF and GYTR improved the morphology of LPS-injured cells and decreased the concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in LPS-induced cells. Moreover, the antioxidant enzyme activity in cells was markedly increased with DQTF and GYTR. The enzymatic hydrolysates of Ruditapes philippinarum were obtained with hydrolysis using pepsin-chymotrypsin-trypsin (PeCTHC) and pepsin-trypsin (PeTHC), respectively. PeCTHC and PeTHC significantly reduced pro-inflammatory cytokines and nitric oxide (NO) in the serum. Additionally, the blood indices and levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) in the livers of mice were markedly improved with RPPs administration. In conclusion, RPPs have preventive and protective effects on acute inflammation, with significant prospects for development in the field of functional foods.

Phytohormones as regulators of heavy metal biosorption and toxicity in green alga Chlorella vulgaris (Chlorophyceae)

The present study was undertaken to test the influence of exogenously applied phytohormones: auxins (IAA, IBA, NAA, PAA), cytokinins (BA, CPPU, DPU, 2iP, Kin, TDZ, Z), gibberellin (GA(3)), jasmonic acid (JA) as well as polyamine - spermidine (Spd) upon the growth and metabolism of green microalga Chlorella vulgaris (Chlorophyceae) exposed to heavy metal (Cd, Cu, Pb) stress. The inhibitory effect of heavy metals on algal growth, metabolite accumulation and enzymatic as well as non-enzymatic antioxidant system was arranged in the following order: Cd>Pb>Cu. Exogenously applied phytohormones modify the phytotoxicity of heavy metals. Auxins, cytokinins, gibberellin and spermidine (Spd) can alleviate stress symptoms by inhibiting heavy metal biosorption, restoring algal growth and primary metabolite level. Moreover, these phytohormones and polyamine stimulate antioxidant enzymes' (superoxide dismutase, ascorbate peroxidase, catalase) activities and ascorbate as well as glutathione accumulation by producing increased antioxidant capacity in cells growing under abiotic stress. Increased activity of antioxidant enzymes reduced oxidative stress expressed by lipid peroxidation and hydrogen peroxide level. In contrast JA enhanced heavy metal toxicity leading to increase in metal biosorption and ROS generation. The decrease in cell number, chlorophylls, carotenoids, monosaccharides, soluble proteins, ascorbate and glutathione content as well as antioxidant enzyme activity was also obtained in response to JA and heavy metals. Determining the stress markers (lipid peroxidation, hydrogen peroxide) and antioxidants' level as well as antioxidant enzyme activity in cells is important for understanding the metal-specific mechanisms of toxicity and that these associated novel endpoints may be useful metrics for accurately predicting toxicity. The data suggest that phytohormones and polyamine play an important role in the C.vulgaris responding to abiotic stressor and algal adaptation ability to metal contamination of aquatic environment.

Prolonged fasting does not increase oxidative damage or inflammation in postweaned northern elephant seal pups

Elephant seals are naturally adapted to survive up to three months of absolute food and water deprivation (fasting). Prolonged food deprivation in terrestrial mammals increases reactive oxygen species (ROS) production, oxidative damage and inflammation that can be induced by an increase in the renin-angiotensin system (RAS). To test the hypothesis that prolonged fasting in elephant seals is not associated with increased oxidative stress or inflammation, blood samples and muscle biopsies were collected from early (2-3 weeks post-weaning) and late (7-8 weeks post-weaning) fasted seals. Plasma levels of oxidative damage, inflammatory markers and plasma renin activity (PRA), along with muscle levels of lipid and protein oxidation, were compared between early and late fasting periods. Protein expression of angiotensin receptor 1 (AT(1)), pro-oxidant (Nox4) and antioxidant enzymes (CuZn- and Mn-superoxide dismutases, glutathione peroxidase and catalase) was analyzed in muscle. Fasting induced a 2.5-fold increase in PRA, a 50% increase in AT(1), a twofold increase in Nox4 and a 70% increase in NADPH oxidase activity. By contrast, neither tissue nor systemic indices of oxidative damage or inflammation increased with fasting. Furthermore, muscle antioxidant enzymes increased 40-60% with fasting in parallel with an increase in muscle and red blood cell antioxidant enzyme activities. These data suggest that, despite the observed increases in RAS and Nox4, an increase in antioxidant enzymes appears to be sufficient to suppress systemic and tissue indices of oxidative damage and inflammation in seals that have fasted for a prolonged period. The present study highlights the importance of antioxidant capacity in mammals during chronic periods of stress to help avoid deleterious systemic consequences.

Improved resistance to serum oxidation in Gilbert's syndrome: A mechanism for cardiovascular protection

Bilirubin is a potent antioxidant, however, uncertainty surrounds its physiological importance. Individuals with Gilbert's syndrome (GS) have increased circulating bilirubin and a reduced prevalence of cardiovascular disease (CVD). The aim of this study was to investigate mechanisms that may link bilirubin to protection from CVD seen in GS by examining markers of antioxidant and oxidative stress status and the susceptibility of serum to oxidation. Nine individuals with GS and twelve controls, matched for age, height and weight, were assessed for plasma antioxidant status, red blood cell antioxidant enzyme activities, plasma malondialdehyde, the susceptibility of serum to copper (Cu 2+) induced oxidation and blood lipid profile. Individuals with GS had significantly elevated unconjugated bilirubin (GS: 26.0 ± 6.4; control: 9.7 ± 3.0 μmol/L; P < 0.001), increased trolox equivalent antioxidant capacity (GS: 1.59 ± 0.07; control: 1.52 ± 0.07 mmol/L trolox Equ; P = 0.035) and ferric reducing ability of plasma (GS: 1.09 ± 0.16; control: 0.92 ± 0.14 mmol/L Fe 2+ Equ; P = 0.024). The lag phase of serum oxidation was significantly longer in the GS group (GS: 121.4 ± 10.5; control: 106.8 ± 14.6 min; P = 0.020) and was positively correlated with the bilirubin concentration ( r = 0.451, P = 0.040). A trend toward elevated HDL:LDL ratio was observed in GS (GS 0.96 ± 0.31; control: 0.73 ± 0.21; P = 0.072). In summary, individuals with GS have an increased circulating antioxidant status and an improved resistance to serum oxidation which may partially explain their reduced prevalence of CVD.

No effect on oxidative stress biomarkers by modified intakes of polyunsaturated fatty acids or vegetables and fruit

Diet may both increase and decrease oxidative stress in the body. We compared the effects of four strictly controlled isocaloric diets with different intakes of polyunsaturated fatty acids (PUFA, 11 or 3% of energy) and vegetables and fruit (total amount of vegetables and fruit 516 or 1059 g/10 MJ) on markers associated with oxidative stress in 77 healthy volunteers (19-52 years). Plasma protein carbonyls (2-aminoadipic semialdehyde residues) and whole-body DNA and nucleotide oxidation (urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine excretion) tended to decrease in all treatment groups with no differences between the diets. The diets did not differ in their effects on red blood cell antioxidative enzyme activities, either. The results suggest that in healthy volunteers with adequate nutrient intakes, 6-week diets differing markedly in the amount of PUFA or vegetables and fruit do not differ in their effects on markers associated with oxidative stress.

Aging and the Brown Norway Rat Leydig Cell Antioxidant Defense System

Previous studies have shown that testosterone production by the Leydig cells of aged Brown Norway rats is reduced from the relatively high levels produced by Leydig cells of young rats and that this reduction is not secondary to decreased serum luteinizing hormone concentration. The free radical theory of aging proposes that imbalance between pro-oxidants and the antioxidant defense system ultimately results in oxidative damage to cellular processes. With this in mind, we hypothesized herein that age-related reductions in steroidogenesis by Brown Norway rat Leydig cells may be associated with the impairment of the antioxidant defense system of these cells. To begin to test this hypothesis, we compared the activities and steady-state mRNA and protein levels of the antioxidant enzymes copper zinc (CuZn) superoxide dismutase (CuZnSOD, SOD1), manganese (Mn) superoxide dismutase (MnSOD, SOD2), and glutathione peroxidase (GPx) and the levels of reduced and oxidized glutathione in Leydig cells isolated from the testes of young (4-month-old) and aged (20-month-old) Brown Norway rats. For some studies, Leydig cells were isolated separately from aged testes that either had regressed because of age-related losses of germ cells or that were nonregressed. SOD (total) and GPx activities were found to decrease significantly with age whether or not the testes were regressed. CuZnSOD and MnSOD mRNA levels decreased with aging, though the magnitude of the decreases were considerably lower than the respective decreases in enzyme activities. GPx mRNA levels also decreased, which is consistent with the decreases seen in enzyme activity. MnSOD protein expression declined with age, and to a lesser extent, CuZnSOD did as well. Reduced and oxidized glutathione also exhibited age-related reductions in cells from both normal and regressed aged testes. The age-related decreases in Leydig cell antioxidant enzyme activities, gene expression, and protein levels and in glutathione were consistent with the hypothesis that the loss of steroidogenic function that accompanies Leydig cell aging may result in part from a decrease in the fidelity of the cellular antioxidant defense system.

Effects of Different Grape Formulations on Antioxidative Capacity, Lipid Peroxidation and Oxidative DNA Damage in Aged Rats

In this study, the freeze-dried powders from whole grapes, pomace and juice of Campbell Early (Vitis labruscana Bailey) were prepared to determine the amount of total flavonoids, vitamins A, C, and E, and dietary fiber. Effects of whole grape, pomace, or juice intakes on their antioxidative capacity and DNA damage were investigated in Sprague-Dawley male rats. A total of 120 rats at 13 mo old and weighing 549 +/- 4 g were blocked into 8 groups according to body weight and raised for 3, 5, or 7 mo with diets containing 2% (w/w) dry powder of three different parts of grapes and 0.02% (w/w) CdCl2. The contents of flavonoids, antioxidant vitamins A and E, and dietary fiber in freeze-dried powder were the highest in grape pomace, but the vitamin C contents were similar among the three powders. In all the 16, 18, and 20-mo-old animals, plasma and liver thiobarbituric acid reactive substances levels of grape-ingesting groups were lower than those of the controls and that of the grape pomace group was the lowest among the groups. Cd administration increased plasma and liver thiobarbituric acid reactive substances levels remarkably; however, Cd+grape groups were lower than the Cd-control group. Red blood cell superoxide dismutase activity of 18- and 20-mo-old rats was higher than that of 16-mo-olds, showing an age-related increase; however, red blood cell catalase and glutathione peroxidase activities decreased with age. Grape diets promoted superoxide dismutase, catalase, glutathione peroxidase activities, and the grape pomace increased the activities most significantly among three different parts of the grape. Cd decreased superoxide dismutase, catalase, glutathione peroxidase activities; however Cd+grape groups showed similar activities to the non-Cd control group. Liver superoxide dismutase activity was decreased with age but catalase activity of 18-mo-old rats was higher than those of 16- and 20-mo-old groups, and glutathione peroxidase activities of 16- and 18-mo-old groups were similar but that of 20-mo-old groups decreased markedly. Grape intake increased these three antioxidative enzyme activities while Cd administration decreased catalase and glutathione peroxidase activities except superoxide dismutase activity. The concentration in the kidney of 8-hydroxy-2'-deoxyguanosine in the 18- and 20-mo-old rats was higher than that in the 16-mo-old groups, and grape intake showed a protecting effect on DNA from age-related or Cd-induced oxidative damage. In conclusion, grape intakes, especially grape pomace with the highest content of flavonoids, beta-carotene, tocopherols and dietary fiber among the three parts, showed the prominent antioxidative capacity of inhibiting age-related or Cd-induced increase of lipid peroxidation and DNA damage effectively, promoting liver and red blood cell antioxidant enzyme activities.

Increased Oxidative Stress and Altered Levels of Antioxidants in Chronic Obstructive Pulmonary Disease

An imbalance between oxidative stress and antioxidative capacity has been proposed to play an important role in the development and progression of chronic obstructive pulmonary disease. We carried out a study to assess the systemic oxidant-antioxidant status in patients with chronic obstructive pulmonary disease (COPD) and relate it to the severity of disease. We measured a wide range of parameters of oxidant-antioxidant balance in leukocytes, plasma and red cells of 82 patients with COPD and 22 healthy non-smoking controls (HNC). Lung function was measured by spirometry. Staging of COPD was done as per the recommended guidelines. Red cell antioxidative enzyme activities were altered, with glutathione peroxidase (GSH-Px) having lower, superoxide dismutase (SOD) having greater and catalase having similar activity in patients as compared to HNC. In plasma, ferric reducing antioxidant power (FRAP) and total protein sulfhydryls were lower and GSH-Px, lipid peroxides measured as MDA-TBA products, and protein carbonyls were higher in the patients as compared to HNC. Plasma total nitrates and nitrites (NO(x)) were similar in the two groups. Superoxide anion (O(2) (*-)) release from leukocytes upon stimulation with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) and total blood glutathione were also higher in patients as compared to HNC. Plasma FRAP had a positive whereas total blood glutathione had a significant negative correlation with the severity of airways obstruction (FEV(1)% predicted). Further, comparisons between clinical stages of severity of COPD revealed significant differences in plasma FRAP and total blood glutathione. Our observations suggest there is a systemic oxidant-antioxidant imbalance in the patients with COPD.

Increased Oxidative Stress in Acute Exacerbations of Asthma

Oxidant-antioxidant imbalance may play an important role in the pathogenesis of asthma, especially during acute exacerbations. To compare the systemic oxidant-antioxidant status in patients with acute exacerbations and stable asthma, we measured a wide range of parameters of oxidant-antioxidant balance in leukocytes, plasma, and red cells of 32 patients with acute exacerbations and 97 patients with stable asthma. These included measurement of superoxide anion generation by leukocytes, lipid peroxidation (measured as TBARS), total nitrates and nitrites, protein carbonyls, and protein sulfhydryls in plasma. Antioxidant status was evaluated by measuring the red cell superoxide dismutase and catalase activity, total blood glutathione, glutathione peroxidase activity in red cell and plasma, and total antioxidant capacity (assessed as ferric reducing antioxidant power) in plasma. Plasma total antioxidant capacity and total protein sulfhydryls were found to be decreased (p < 0.01), whereas plasma lipid peroxides were found to be increased (p < 0.05), in acute exacerbations of asthma. No significant differences were found in plasma glutathione peroxidase, protein carbonyls, and total nitrates and nitrites, red cell antioxidative enzyme activities, superoxide anion release from leukocytes, and total blood glutathione between the two groups (p > 0.05). Our observations suggest that acute exacerbations of asthma are associated with increased oxidative stress that is evident from some of the parameters in the plasma. Failure to observe simultaneous changes in all parameters of oxidative stress may be due to the possibility of their responses being dissociated in time or compensatory changes occurring in some of these.

Oxidative stress in Rett syndrome

The investigation of parameters that might influence the neurological evolution of Rett syndrome might also yield new information about its pathogenic mechanisms. Oxidative stress caused by oxygen free radicals is involved in the neuropathology of several neurodegenerative disorders, as well as in stroke and seizures. To evaluate the free radical metabolism in Rett syndrome, we measured red blood cell antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase) and plasma malondialdehyde, as lipid peroxidation marker in a group of patients with Rett syndrome. No significant differences were observed in erythrocyte glutathione peroxidase, glutathione reductase and catalase activities, between the Rett syndrome patients and the control group. Erythrocyte superoxide dismutase activities were significantly decreased in Rett syndrome patients ( P<0.001) compared with the control group. Plasma malondialdehyde concentrations were significantly increased in Rett syndrome patients ( P<0.001). An unbalanced nutritional status in Rett syndrome might explain the reduced enzyme activity found in these patients. Our results suggest that free radicals generated from oxidation reactions might contribute to the pathogenesis of Rett syndrome. The high levels of malondialdehyde reflect peroxidative damage of biomembranes that may contribute to progressive dementia, impaired motor function, behavioural changes, and seizures, in Rett syndrome. We found a probable relationship between the degree of oxidative stress and the severity of symptoms, which should be further investigated with a larger number of patients in different disease stages.

An insulin sensitizer improves the free radical defense system potential and insulin sensitivity in high fructose-fed rats.

Recently there has been growing interest in the effects of antioxidants on insulin activity. In the present study, we investigated the effect of metformin on free radical activity and insulin sensitivity in high fructose-fed rats, a diet that leads to insulin resistance. The animals were divided into four groups (n = 16 per group; experiment duration = 6 weeks): the control (C) group received a standard diet; the control metformin (CM) group was fed a control diet and received metformin (200 mg x kg(-1) x day(-1) in water); the fructose control (FT) group was fed a diet in which fructose composed 56.8% of the total carbohydrates; and the fructose metformin (FM) group received high-fructose diet and metformin (200 mg x kg(-1) x day(-1) in water). The glucose clamp technique was used to determine insulin sensitivity in eight animals per group. Metabolic and oxidative stress parameters were measured in the remaining rats. In the FT rats, insulin resistance, lower red cell CuZn superoxide dismutase activity and lower blood reduced glutathione were observed. Metformin treatment improved both the insulin activity and the antioxidant defense system. In the CM group, metformin had no effect on metabolic parameters, but improved red cell antioxidant enzyme activities and the blood GSH level, which suggests that it has an antioxidant activity independent of its effect on insulin activity.

Red blood cell antioxidant enzymes in age-related macular degeneration.

Oxidative damage has been proposed to be involved in the pathogenesis of age-related macular degeneration (ARMD). The purpose of this study was to evaluate whether red blood cell antioxidant enzyme activity correlates with severity of aging maculopathy in affected individuals. Blood samples were obtained from 54 patients with varying severity of aging maculopathy and 12 similarly aged individuals with normal ophthalmoscopic examination. Macular findings were graded according to a modification of the method described for the Age-Related Eye Disease Study. (AREDS). The activities of superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, and glutathione reductase were measured in red blood cells. Haemoglobin content of whole blood was measured, and enzyme activity was determined per mg haemoglobin. Multiple regression analysis and ordinal logistic regression analysis were performed to determine whether antioxidant enzyme activity was associated with severity of ARMD. No significant association between disease severity of ARMD and antioxidant enzyme activity was identified for any of the enzymes. These results do not provide evidence for a relation between oxidative stress, as measured by antioxidant enzyme activity in red blood cells, and disease severity in ARMD.

Heart and red blood cell antioxidant status and plasma lipid levels in the spontaneously hypertensive and normotensive Wistar–Kyoto rat

Heart and red blood cell endogenous antioxidant status and plasma lipids were investigated in hypertensive, 14-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats fed a standard commercial rat chow. Specific heart and red blood cell antioxidant enzyme activities, as well as the susceptibility of tissues to H2O2-induced glutathione (GSH) depletion and lipid peroxidation, were measured. Systolic blood pressure in SHR was greater than in WKY rats at 13 weeks of age (197 +/- 12 vs. 132 +/- 14 mmHg (1 mmHg = 133.3 Pa); p < or = 0.05), confirming the presence of hypertension in SHR. Red blood cell catalase (CAT) and superoxide dismutase (SOD) activities were greater (p < or = 0.05) in SHR than WKY rats. Red blood cell CAT activity was positively correlated (r = +0.634; p = 0.026) with SOD, which in turn was correlated (r = +0.709; p = 0.049) with systolic blood pressure. Heart SOD activity was higher (p < or = 0.05) in SHR, while glutathione reductase (GSSG-Red) activity was lower (p < or = 0.05) than in WKY rats. This reduced ability to recycle GSH in the heart coincided with greater (p < or = 0.05) levels of H2O2-induced lipid oxidation products in SHR. Plasma total cholesterol and triacylglycerol levels were lower (p < or = 0.05) in SHR than WKY rats, with no visible signs of atherosclerosis in either SHR or WKY rats. In summary, hypertension in SHR was associated with alterations in antioxidant enzyme profiles of red blood cells and heart, with the latter showing an increased susceptibility to in vitro lipid oxidation. Although hypertension is a recognized factor in the development of human atherosclerosis, spontaneously hypertensive rats did not exhibit signs of aortic plaque, reflecting the resistance of this species to the development of atherosclerosis.

In vitro effects of hyperoxia on alveolar type II pneumocytes: inhibition of glutathione synthesis increases hyperoxic cell injury.

An in vitro model of alveolar epithelial oxidant injury was developed based on exposure to hyperoxia of cultured guinea pig type II pneumocytes using a biphasic cell culture system in aerobiosis. The present study investigates the roles of intracellular antioxidant enzymes and of glutathione in providing protection against hyperoxia. A 2-day type II cell culture in normoxia was associated with a significant decrease in protein, catalase, and Cu-Zn SOD cell content, whereas ATP cell content, Mn-SOD, and glutathione peroxidase (GPx) activities did not change and glutathione cell content significantly increased. Exposure of type II cells to hyperoxia did not induce significant changes in cell content in protein, SOD, catalase, GPx, or glutathione cell content when compared to control cells (exposed to normoxia). With ATP cell content expressed as a cell injury index (CII), type II cell injury was found to increase with increasing O2 concentrations. Indeed, a 2-day 50% O2 and 95% O2 exposure resulted in a CII of -7.5 +/- 6.2% and 17.9 +/- 5.9%, respectively, LDH release by type II cells was not significantly increased after hypoxic exposure. Cell injury effects of hyperoxia did not correlate with the endogenous antioxidant enzyme activities (SOD, Mn-SOD, catalase). In marked contrast, there was a significant correlation between the CII and total glutathione content of type II cells (p < .01). This correlation was largely due to the close relationship between CII and reduced glutathione. Hyperoxic induced cell injury (as demonstrated by CII > 0) was clearly associated with significantly lower intracellular glutathione level when compared to experiments without hyperoxia induced cell injury (CII < 0). In addition, in the presence of buthionine sulfoximine (BSO), the ability of type II cells to synthetize new glutathione was severely impaired, whereas ATP cell content and cell antioxidant enzyme activities did not change. As a consequence, the reduction of intracellular glutathione significantly increased the susceptibility of cells to hyperoxia injury (p < .05). The results strongly support the hypothesis that the regulation of glutathione levels is an important mechanism in protecting hyperoxia-induced type II cell injury.

Antioxidant enzyme activity in alveolar type II cells after exposure of rats to hyperoxia.

The activity of antioxidant enzymes were measured in alveolar type II cells isolated from control and 85% oxygen-exposed rats to determine if type II cells, an oxygen-resistant lung cell type had constitutively high enzyme activities and to measure the effect of hyperoxia on these antioxidant enzyme. Type II cells were isolated from lungs of control rats and rats exposed to 85% O2 for 7 days. In whole lungs of rats exposed to 85% oxygen there is an increase in activity (per lung or per mg lung DNA) in the antioxidant enzymes CuZn superoxide dismutase, Mn superoxide dismutase, catalase, glutathione peroxidase and glucose-6-phosphate dehydrogenase. Oxygen exposure significantly increased (p less than 0.05) all type II cell antioxidant enzyme activities when expressed per mg DNA. The protein content of oxygen exposed type II cells increased 25% from (63.9 +/- 4.8 micrograms/10(6) cells to 79.6 +/- 4.2 micrograms/10(6) cells, p less than 0.05). When type II cell enzyme activities were expressed in U/mg cell protein, only CuZn superoxide dismutase and Mn superoxide dismutase increased in activity following oxygen exposure (by 43% and 28% relative to air exposed lung type II cells, respectively, p less than 0.05). This suggested that most lung cell antioxidant enzymes increased in activity following oxidant stress in proportion to increased cell mass. CuZn and Mn superoxide dismutase increased activity to an extent greater than the increase in type II cell protein content after oxygen exposure. Alveolar macrophages lavaged from control and oxygen-exposed rats were also evaluated, and they had no significant change in CuZn and Mn superoxide dismutase activities. Type II cells accounted for 10% and 17% of alveolar cells in control and oxygen treated rats. By knowing the antioxidant enzyme activities in type II cells, the total enzyme activity of whole lung and the number of type II cells in control and oxygen exposed rats from morphometric data, we calculated the percent of whole lung enzyme activity accounted for by type II cells. Type II cells accounted for a high percentage of lung glucose-6-phosphate dehydrogenase (58% in control rats, 65% in oxygen exposed rats) but a low percentage of Mn superoxide dismutase (4% in control rats, 6% in oxygen exposed rats).

Biochemical and cellular aspects of pulmonary oxygen toxicity

Pulmonary oxgen toxicity results in intraalveolar hemorrhage and edema following the breakdown of the alveolar-capillary barrier. Hyperoxia causes increased production of partially reduced species of oxygen in lung cells critical for maintaining the integrity of the alveolar-capillary barrier, the capillary endothelial cell and the alveolar epithelium. In vitro studies of subcellular organelles isolated from lung including mitochondria, microsomes and nuclei show that oxygen radical production by these organelles increases as a function of oxygen tension. Morphological alterations of lung cell organelles in early stages of oxygen toxicity probably reflect cell injury induced by toxic reactions of relatively high local concentrations of reactive oxygen species. Cell injury and secondary inflammatory responses will occur when edogenous antioxidant defenses are overwhelmed. Oxygen-injured lung cells release paracrine mediators which effect the growth and differentiation of other lung cells. A number of factors can modify pulmonary oxygen toxicity, including the maturational state of the lung, infiltration of phagocytic cells, liposome-mediated augmentation of lung cell antioxidant enzyme activities and commonly prescribed medications.