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S G Jenkinson

Publications and source records attributed to S G Jenkinson.

At least 55 records · Page 3Linked to original sources
PubMed1989

Effects of selenium deficiency on glutathione-induced protection from hyperbaric hyperoxia in rat.

Exposure of rats to 100% O2 at high pressure (greater than 2.0 ATA) results in generalized convulsions and death within several hours. The tripeptide, glutathione, has been shown to protect rats exposed to hyperbaric hyperoxia with delayed onset of seizures and prolonged survival. To investigate the hypothesis that glutathione exerts its protective effects via the glutathione redox cycle, we injected selenium-deficient rats and their selenium-supplemented controls with either glutathione (1 mmol/kg) or an equivolume of saline before exposure to 100% O2 at 4 ATA. Selenium-deficient rats exhibit marked reduction in liver glutathione peroxidase activity (GSH-Px). Glutathione administration significantly delayed both the onset of seizures and time to death in the control animals. In selenium-deficient rats, however, glutathione administration was not protective, having no significant effects on time to seizure or time to death. We also measured changes in glutathione concentrations in lung, liver, and brain of these same groups of animals exposed either to hyperbaric hyperoxia or to room air. In control rats, lung and brain glutathione concentrations did not change with the hyperbaric exposure regardless of glutathione pretreatment status, but hepatic glutathione concentration declined significantly during the exposure when glutathione was not supplied. If these animals were pretreated with glutathione, the decline in hepatic glutathione concentrations did not occur. In selenium-deficient rats, the hyperbaric exposure did not result in changes in lung, brain, or liver glutathione concentrations either in the glutathione-pretreated or in the saline-pretreated animals. Exogenous GSH administration does not protect selenium-deficient rats from hyperbaric hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of hyperoxia and vitamin E on the fatty acid composition of rat lung microsomes and mitochondria.

Peroxidation of lung membrane lipids in vitro produces very specific changes in lung membrane fatty acid content with some fatty acids being affected more than others. We performed a series of experiments to determine the changes occurring in fatty acid composition in lung microsomes and mitochondria during an in vivo hyperoxic exposure. Hyperoxia did produce specific changes in the relative content of fatty acids present in lung microsomes and mitochondria of both vitamin E-supplemented and vitamin E-deficient rats. Changes were noted to occur in saturated and polyunsaturated fatty acids. The total amount of lung lipids extractable in the microsomal fractions decreased after hyperoxia in both the vitamin E-supplemented and the vitamin E-deficient animals with no changes occurring in extraction of lung mitochondrial total lipids. Decreases in lung mitochondrial fatty acids caused by hyperoxia occurred in the same fatty acids in both the vitamin E-supplemented and the vitamin E-deficient animals with few polyunsaturated fatty acids (PUFA) being affected. Decreases in lung microsomal fatty acids occurring during hyperoxia were different in the vitamin E-supplemented animals from those in the vitamin E-deficient animals with many more PUFA decreasing in the vitamin E-deficient group. The greatest number of PUFA found to decrease after hyperoxia when comparing all the different groups occurred in the microsomal fraction of the vitamin E-deficient rats. These data suggest that vitamin E-deficient animals have increased peroxidation of lung microsomal PUFA or a decrease in production of lung microsomal PUFA in vivo during a hyperoxic exposure.

Animals↗
PubMed1989

Free radical effects on lung metabolism.

Exposure to hyperoxia or a number of different environmental toxins can result in free radical-mediated lung injury. Specific toxins and their activated breakdown products can produce free radicals and markedly change normal lung metabolism by reacting with cell membranes, intracellular proteins, and nucleic acids. Endogenous production of free radicals by polymorphonuclear leukocytes sequestered in the lung can also lead to lung damage. Numerous intracellular and extracellular free radical defenses are present in human lung to detoxify these oxygen species as they are being formed. Lung injury will begin to occur if free radical production overcomes lung antioxidant defenses.

Free Radicals↗
PubMed1988

BCNU-induced protection from hyperbaric hyperoxia: role of glutathione metabolism.

To explore the role of the glutathione oxidation-reduction cycle in altering the sensitivity of rats to the effects of hyperbaric hyperoxia, we administered N,N-bis(2-chloroethyl)-N-nitrosourea (BCNU) to decrease tissue glutathione reductase activity. We then exposed these animals and their matched vehicle-treated controls to 100% O2 at 4 ATA. Animals that received BCNU and were immediately exposed to hyperbaric O2 showed enhanced toxicity by seizing earlier in the exposure than controls. Animals that received BCNU 18 h before the hyperbaric O2 exposure were paradoxically protected from the effects of the exposure with a prolongation of their time to initial seizure and a marked increase in their survival time during the exposure. Tissue glutathione concentrations were also measured in the various groups and the hyperbaric O2 exposure produced marked decreases in hepatic glutathione levels in all control animals. In animals treated with BCNU 18 h before exposure, hepatic glutathione concentrations also decreased, but the concentrations had significantly increased during the 18-h waiting period, allowing these animals to maintain hepatic levels in the normal range even during their hyperbaric exposures. We conclude that treatment of rats with BCNU 18 h before exposure to hyperbaric hyperoxia results in enhanced protection of the animals during the exposure.

Animals↗
PubMed1988

Glutathione disulfide formation occurring during hypoxia and reoxygenation of rat lung.

To study changes in glutathione redox status as an indicator of oxidant stress during hypoxia and reoxygenation, we perfused isolated rat lungs with a high or low oxygen perfusate and measured the release of total glutathione and glutathione disulfide (GSSG) into the perfusate. Lungs were perfused for a 20-minute baseline period with a perfusate equilibrated with 95% O2 and 5% CO2 and ventilated with a 95% O2 and 5% CO2 gas mixture. Only very low amounts of oxygen were measurable in this hypoxic perfusate. The lungs were then perfused from a second reservoir containing perfusate equilibrated with 95% N2 and 5% CO2 and ventilated with a 95% N2 and 5% CO2 gas mixture. After the period of hypoxia, the lungs were reperfused with the 95% O2 and 5% CO2 equilibrated perfusate and ventilated with a 95% O2 and 5% CO2 gas mixture for the remainder of the experiment. Glutathione was measured in the perfusate serially throughout the experiment, and lactic dehydrogenase (LDH) was also measured to assess cell membrane rupture during the infusion. GSSG release remained stable in the baseline and hypoxic period but rose significantly in the reoxygenation period, to concentrations approximately two times basal release. Lung tissue concentrations of GSSC also rose in the reoxygenation period. Decreasing lung glutathione reductase activity by pretreating animals with 1,3-bis-2-chloroethyl)-1-nitrosourea (BCNU) increased GSSG release into the perfusate during reoxygenation. We conclude that GSSG formation and release is increased in the lung during the reoxygenation period after lung hypoxia, suggesting the presence of hydroperoxide and free radical metabolism. These data support the hypothesis that alterations in lung metabolism occur during hypoxia that allow free GSSG formation and release during the reintroduction of oxygen.

Animals↗
PubMed1988

Oxygen toxicity.

Ventilating patients with elevated oxygen tensions alters normal respiratory physiology and may damage lung tissue, depending on coexisting host and iatrogenic factors. Pulmonary oxygen toxicity begins at a cellular level when the generation of reduced oxygen intermediates exceeds local defenses. The mainstay of therapy is prevention. Supplemental oxygen should be prescribed at the lowest concentration possible that will still allow adequate tissue oxygenation. Presently, no specific therapeutic interventions are approved for use in humans to treat pulmonary oxygen toxicity. New agents that act as free radical scavengers or reduce free radical formation may prove useful in future clinical trials based on many of the scientific studies summarized in this review.

Animals↗
PubMed1988

Glutathione concentrations in rat lung bronchoalveolar lavage fluid: effects of hyperoxia.

Glutathione concentrations were measured in rat bronchoalveolar lavage fluid (BALF) obtained from normal rats and rats exposed to a fraction of inspired oxygen (FiO2) of 0.8 for up to 5 days. We also perturbed rat lung glutathione concentrations by administering the compound diisopropylidene acetone (phorone) to a separate group of animals and correlated changes in BALF glutathione with changes in lung tissue glutathione. We found that reduced glutathione is present in normal rat BALF but glutathione disulfide is extremely low. Increases in lung tissue glutathione concentration and in BALF glutathione concentration occurred after 5 days of exposure to hyperoxia. Animals treated with phorone exhibited decreases in lung glutathione concentration two hours after dosing and increases in lung glutathione concentration 24 hours after dosing. Rat BALF obtained from phorone-treated animals at 2 or 24 hours after administration revealed that changes in BALF glutathione concentrations reflected changes in lung tissue glutathione concentration. The presence of glutathione in lung lavage fluid suggests that the compound could be playing an extracellular role in the lung, either as an antioxidant or as a coenzyme for other glutathione-related enzymatic reactions.

Animals↗
PubMed1987

Nutritional changes in nonhuman primates during mechanical ventilation.

To characterize the baseline nutritional changes occurring in healthy baboons receiving an acute lung injury, we prospectively evaluated serial nutritional changes in eight adult baboons that received oleic acid (0.08 mL/kg) and then required mechanical ventilation for a period of 8 d. The animals were given hypocaloric feeding. Nutritional assessment included the measurement of changes in muscle mass and changes in visceral protein concentration and plasma lipids. Both serum protein and albumin concentrations decreased for 3 d after mechanical ventilation began but then remained stable. The animals exhibited a marked increase in bronchoalveolar lavage fluid (BALF) protein concentrations after receiving oleic acid. We conclude that previously healthy baboons receiving only dextrose infusion during mechanical ventilation have marked decreases in serum albumin occurring after the lung injury. Decreases in albumin occur very early and may represent pooling of albumin in the lung after the oleic acid injury.

Animals↗
PubMed1987

Rat lung glutathione release: response to oxidative stress and selenium deficiency.

We performed experiments to characterize the glutathione-dependent metabolism occurring during tert-butyl hydroperoxide infusion in isolated perfused rat lungs and to examine the effect of selenium deficiency on this metabolism. Selenium deficiency resulted in decreased lung glutathione peroxidase activity but normal glutathione reductase activity and glutathione content. Infusion of the hydroperoxide into control lungs caused a proportional increase in tissue glutathione disulfide (GSSG) concentration and release of GSSG into the perfusate up to an infusion rate of 250 nmol of tert-butyl hydroperoxide X min-1 X 100 g body wt-1. Infusion rates greater than this resulted in continued rise of tissue GSSG concentrations but GSSG release into the perfusate plateaued. Infusion of tert-butyl hydroperoxide into selenium-deficient rat lungs resulted in much lower concentrations of tissue GSSG and GSSG release into the perfusate; however, release in the selenium-deficient rat lung was also found to be saturable at infusion rates of 450 nmol of tert-butyl hydroperoxide X min-1 X 100 g of body wt-1. Selenium deficiency in the rat decreases the rate of reduction of infused tert-butyl hydroperoxide by glutathione and may predispose the lung to free radical damage.

Animals↗
PubMed1987

Species variation in lung antioxidant enzyme activities.

Exposure of several different animal models to O2-induced lung injury has revealed marked differences in sensitivity of various species to O2 damage. These differences may be due in part to variation of cellular antioxidant defenses. To characterize lung antioxidant enzyme activities in different species, we measured lung activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GSH S-trans) in rat, hamster, baboon, and human lung. Soluble lung fractions were also fractionated on Sephadex G-150-S columns and GSH-Px activity was measured using both cumene hydroperoxide and H2O2. This was done to evaluate non-Se-dependent GSH-Px activity in these lung samples. Human lung was obtained at surgery from patients undergoing lobectomy or pneumonectomy for localized lung tumors. SOD activity was similar for all four groups. GSH-Px activity was higher in rat lung than baboon or hamster lung. Lung CAT activity was variable with the highest activity present in the baboon which revealed a lung CAT activity 10 times higher than activity present in the rat. Lung GSH S-trans activities were higher in hamster, baboon, and human lung than in rat lung. Non-Se-dependent GSH-Px was present in rat lung but absent in hamster, baboon, and human lung. We conclude that the hamster was the best model of the animals studied for mimicking human lung antioxidant enzyme activities. Rat lung antioxidant enzyme activities were markedly different from any of the other species examined.

Animals↗
PubMed1987

Effects of copper deficiency on carbon tetrachloride-induced lipid peroxidation.

To investigate the hypothesis that copper deficiency in the rat could result in increased susceptibility to CCl4-induced lipid peroxidation caused by decreased free radical defenses, we performed a series of experiments administering CCl4 to copper-deficient and control rats. Peroxidation after CCl4 administration was monitored by measuring the evolution of expired ethane in closed metabolic chambers. Rats were fed one of two copper-deficient diets based on either evaporated milk or powdered milk. Compared with control values, liver copper content, liver superoxide dismutase activity, and plasma ceruloplasmin level were significantly decreased in copper-deficient rats fed either of the diets. Liver glutathione peroxidase activity was also decreased in the copper-deficient rats fed the evaporated milk diet. Ethane evolution was markedly increased in both copper-deficient groups as compared with their controls. Copper deficiency was also found to produce increases in hepatic iron concentrations, but normal rats loaded with iron dextran to increase hepatic iron concentrations into a range similar to that found in the copper-deficient rats did not exhibit increased ethane evolution after CCl4 administration. Copper deficiency in the rat results in increased CCl4-induced lipid peroxidation.

Animals↗
PubMed1986

Rat lung microsomal lipid peroxidation: effects of vitamin E and reduced glutathione.

Lung microsomal membranes that contain the redox active components associated with the mixed-function oxidase system can be peroxidized in vitro. To investigate the characteristics of rat lung microsomal lipid peroxidation, we performed experiments using a variety of peroxidation initiators and microsomes obtained from normal and vitamin E-deficient rats. We found that lung microsomes obtained from normal rats are peroxidized much less than liver microsomes obtained from the same animals. Only initiation systems using very high concentrations of ferrous iron produced any significant peroxidation of normal rat lung microsomes. Lung microsomes obtained from vitamin E-deficient rats were found to be much more susceptible to peroxidation. Glutathione (GSH) was effective in inhibiting peroxidation when lung microsomes from normal rats were peroxidized. GSH was not effective in decreasing peroxidation when microsomes from vitamin E-deficient rats were peroxidized in the same system. We conclude that both GSH and vitamin E protect lung microsomal membranes from peroxidation. Glutathione protection appears to be related to the presence of a sulfhydryl group.

Animals↗
PubMed1986

Effects of bacterial endotoxin on protecting copper-deficient rats from hyperoxia.

The administration of very low doses of bacterial endotoxin protects rats during exposure to hyperoxia and is associated with the induction of lung antioxidant enzyme activities. Copper-deficient rats have increased susceptibility to O2 toxicity, which may be related to their decreased lung superoxide dismutase activity (SOD) or decreased plasma ceruloplasmin concentrations. To determine whether endotoxin can protect against hyperoxia in this susceptible model, we exposed copper-deficient and control rats to a fractional inspiratory concentration of O2 greater than 0.95 for 96 h after pretreatment with 500 micrograms/kg of bacterial endotoxin or phosphate-buffered saline (PBS). Mortality in the copper-deficient and control rats given PBS and exposed to O2 for 96 h was 100%. Copper-deficient rats died significantly earlier during the exposure than controls. No mortality occurred in either group treated with endotoxin and hyperoxia despite the decreased activity of copper-dependent enzymes in the copper-deficient rats. Copper-deficient rats treated with endotoxin and exposed to hyperoxia did increase lung Cu-Zn-SOD activity, but activity remained below levels found in air-exposed controls. Mn-SOD activity was found to be induced above air-exposed controls in the copper-deficient rats treated with endotoxin and exposed to hyperoxia. Hyperoxic exposure resulted in a marked increase in plasma ceruloplasmin concentrations in the control rats, but no increases in ceruloplasmin occurred in the copper-deficient animals. Endotoxin protects copper-deficient rats from hyperoxia despite their decreased lung Cu-Zn-SOD activity, and decreased plasma ceruloplasmin.

Animals↗
PubMed1986

Respiratory gases.

Respiratory gases have access to the human circulation by diffusing through alveolar walls into pulmonary capillaries. Because of this circulatory access, these gases can act like other types of drugs, and can produce effects both locally in the lungs and systemically in distant organs or tissues. This article reviews the metabolism, pharmacology, and therapeutic use of the three most common gases used in the practice of respiratory medicine: oxygen, carbon dioxide, and helium.

Carbon Dioxide↗
PubMed1985

The use of cefotaxime in the treatment of gram-positive pneumonias.

A single-blind, prospective, randomized comparison of cefotaxime and cefazolin was conducted in 356 patients with gram-positive pneumonias. Clinical cure was achieved in 95.9% of patients receiving cefotaxime and 94% of patients receiving cefazolin. In a sub-group of patients with Staphylococcus aureus pneumonia, clinical cure was obtained in 31 of 37 patients treated with cefotaxime and all of six patients treated with cefazolin. Cefotaxime was well tolerated, safe, and efficacious. These data support the use of cefotaxime as an initial single antibiotic in treating patients with gram-positive pneumonias due to susceptible organisms.

Adolescent↗
PubMed1985

Pneumothorax.

Pneumothorax is a common clinical problem encountered by both surgical and medical physicians. Air leaks into the pleural space occur either spontaneously or as a result of traumatic tears in the pleura following chest injury or surgical procedures. Therapy is directed at removing air from the pleural space, re-expanding the underlying lung, and preventing recurrences.

Adult↗
PubMed1984

Enhanced pulmonary toxicity in copper-deficient rats exposed to hyperoxia.

The antioxidant enzyme superoxide dismutase (SOD) found in the cytosol of eucaryotic cells and the plasma protein ceruloplasmin are copper containing proteins though to be important in providing protection from oxygen toxicity. To investigate the hypothesis that copper deficiency in the rat could result in decreased lung SOD activity and plasma ceruloplasmin concentration resulting in increased susceptibility to O2 lung damage, we performed a series of experiments exposing copper-deficient and control rats to normobaric and hyperbaric hyperoxia. Lung SOD activity in the copper-deficient rats was found to be 56% of control and ceruloplasmin content was 6% of control. The copper-deficient rats exhibited increased mortality and enhanced pulmonary toxicity as evidenced by increased pathologic damage and lung edema during the normobaric exposure to 85% O2. Copper-deficient animals also showed increased susceptibility to a hyperbaric exposure of 4 ata of 100% O2 with a decreased time of survival. The copper-deficient rat represents a new model for the study of oxidant injury.

Animals↗