Chronic ethanol feeding to normal rats (10g/kg body weight) produces changes in the rate of respiration, P/O ratio, and respiratory control ratio (RCR), when either glutamate and malate or succinate was used as substrate. The activities of NADH dehydrogenase and cytochrome c oxidase were significantly decreased by ethanol administration compared with the control levels. Succinate dehydrogenase was not affected by ethanol. Similar findings were obtained with intact mitochondria or submitochondrial particles. No significant difference was observed in membrane potential of submitochondrial particles. In addition, cytochrome b, c, and aa3 content of mitochondria was significantly decreased by ethanol feeding. Administration of Berberis aristata (2ml extract/100g body weight) along with ethanol provided a significant protection against most of the alterations in mitochondria induced by ethanol. Ethanol-induced inhibition was almost relieved with respect to the rate of respiration, P/O ratio, RCR and NADH dehydrogenase by the administration of Berberis aristata extract. Inhibition of cytochrome c oxidase was relieved to some extent (38% inhibition was observed compared with ethanol alone (59%)). The decrease in amounts of cytochromes could not be relieved completely by Berberis aristata, but there was a significant increase in their levels compared with those of the ethanol-administered group.
This study was performed to determine plasma lipid changes and antioxidant status in relation to cholesterol content and fatty acid distribution in the aorta of rats after long-term ovariectomy (OV). After 12 months, OV induced in rat plasma a significant increase in glucose, total cholesterol, and triglycerides compared with the corresponding values for the control rats (C) of the same age (p<0.0005, p<0.005, p<0.000S, respectively). These changes were associated with a significant increase in lipid peroxide level (p<0.05) and a significant decrease in vitamin E in the plasma from group OV compared with the group C level (p<0.0001). Conversely, OV after 7 and 12 months induced a significant increase in vitamin C (p<0.001, p<0.0001, respectively). Concerning plasma fatty acid distribution, after 12 months, OV caused a significant increase in gamma and dihomo gamma linolenic acid (p<0.0005, p<0.05, respectively). These changes were associated with a significant increase in aortic cholesterol in group OV (p<0.0005), and a significant decrease in the percentage of arachidonic acid (p<0.005) and of the total amount of fatty acids of the n-3 series (p<0.0001) and plasmalogen fatty acids (C16:0, p<0.005; C 18:0, p<0.05) compared with the corresponding values for group C. These results show that OV induced, independently of any effects of aging, plasma-specific lipid alterations with dysregulation of oxidative status, which could be crucial in the development of atherothrombotic disease.
Oral administration of methacrylonitrile (MeAN) (100mg/kg body wt/day) to rats for 14 days damaged the lung tissue and altered the bronchoalveolar lavage (BAL) angiotensin-converting enzyme activity (ACE) and levels of phospholipids and surfactant phospholipids. However, there was no alteration in BAL lactate content or lactate dehydrogenase activity. A significant increase in the phosphatidylcholine content in the extracellular surfactant indicates Type-II cell proliferation. MeAN caused the lung injury by increasing alveolar capillary permeability and promoting the accumulation of surfactant phospholipids, which may lead to serious conditions such as fibrosis.
The modifying effects of the plant products neem and turmeric during the pre-initiation and post-initiation phases of oral carcinogenesis induced by 4-nitroquinoline 1-oxide were investigated in male Wistar rats. The chemopreventive potential of these plant products was biomonitored by measurement of lipid peroxidation and antioxidant status in the host liver and circulation of tumor-bearing animals. Both neem and turmeric significantly decreased the formation of lipid peroxides and enhanced the levels of enzymic and non-enzymic antioxidants in the pre-initiation as well as post-initiation phases. We speculate that the anticarcinogenic effect of these plant products is partly related to their antioxidant functions.
In our study to elucidate the biochemical basis of macrophage activation, we noted a transient surge (within 24h) in neutrophil number in the peritoneal cavity following the injection of thioglycollate. By day 2 the peritoneal cell population consisted predominantly of vacuolated macrophages. In order to understand the possible cause of the above short-lived increase in neutrophils, we compared the capacity to produce toxic free radicals (by measuring luminol-dependent chemilu-minescence) and the activities of detoxification enzymes, namely, glutathione peroxidase and glutathione reductase, between neutrophils (day-1 cells) and the day-2 cells, which were predominantly macrophages. The results show that the neutrophils obtained 1 day after elicitation by thioglycollate produced an intense burst of luminol-dependent chemilu-minescence, approximately 7-fold greater than that of the day-2 macrophages. This was true despite a markedly enhanced oxygen consumption by the latter compared with that by the neutrophils. In addition there were marked differences in the onset and duration of the response. Investigations on the activities of detoxification enzymes, especially glutathione peroxidase and glutathione reductase, which are known to be coupled to the oxidative segment of the pentose phosphate pathway, revealed neutrophils to have a reduced capacity to detoxify free radicals and peroxides in comparison with elicited macrophages. These findings suggest that the neutrophils, despite their enhanced capacity to emit toxic free radicals and peroxides, are less efficient in protecting themselves, which ultimately may cause cell death and, as a consequence, a decline in their cell number at the site of inflammation.
Prolonged skeletal muscle ischemia has been reported in acute arterial occlusion and crush syndrome. It often induces progressive edema and necrosis and occasionally life-threatening systemic complications, such as hypotension, hyperkalemia, acidosis, pulmonary edema, and acute renal failure. As in other organs, ischemic injury in skeletal muscle is initiated during hypoxia and is aggravated by reoxygenation during blood reperfusion. This study aimed at examining the protective effect of antioxidative enzymes, superoxide dismutase and catalase, on ischemia-reperfusion injury in skeletal muscle. Skeletal muscles in rat hindlimb were subjected to in vivo ischemia by clamping both the infrarenal aorta and the bilateral femoral arteries for 4h and to the subsequent blood reperfusion for 1h under profound anesthesia with pentobarbitone. An attempt was made to suppress the muscle injury by infusing superoxide dismutase and catalase 5min before starting reperfusion. Tissue water content was significantly increased by reperfusion. The increase in the water content was suppressed by the addition of those scavengers. Plasma levels of creatine phosphokinase and lactate dehy-drogenase were increased by ischemia and reperfusion. Addition of the scavengers did not suppress these increases, indicating that scavengers were not effective in suppressing the cellular injury, which might have begun during the ischemia and which might have been exacerbated by the reperfusion. Mitochondrial oxidative phosphorylation was significantly suppressed by ischemia and reperfusion. Such scavengers restored the inhibited mitochondrial function. These results indicate that the radical scavengers tested were effective to protect mitochondrial functions against ischemia-reperfusion insults. Although the present study was carried out on an animal model, administration of these radical scavengers may be effective to reduce injury due to acute arterial occlusion and crush syndrome.
In the present work, we studied the antioxidant status in the blood of a group (n=29) of rheumatoid arthritis (RA) patients and compared it with that of a control group (n=30). There was a significant increase (p<0.001) in the plasma lipid peroxide level, but no change in the plasma ascorbic acid level, when the RA group was compared with the control group. There was a significant decrease in reduced glutathione (GSH, p<0.01) and in glutathione peroxidase (GPX, p<0.05) and superoxide dismutase (SOD, p<0.001) activities in the hemolysate of RA patients when compared with the control group values. A good correlation was obtained between the parameters estimated in the hemolysate. This study reflects the oxidative stress as a result of altered antioxidant status in the blood of RA patients, which findings may have implications in the pathogenesis of the disease.