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Biomedical subjects

S K Nelson

Publications and source records attributed to S K Nelson.

At least 19 recordsLinked to original sources
PubMed2001

A novel iron chelator in combination with a P-selectin antagonist prevents ischemia/reperfusion injury in a rat liver model.

BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury is associated with early and late graft failure after liver transplantation. A major mechanism is leukocyte adhesion to endothelium followed by release of reactive oxygen intermediates. We examined whether desferriexochelin 772SM (D-Exo), a lipid soluble iron chelator that prevents hydroxyl radical formation, can enhance the capacity of recombinant P-selectin glycoprotein ligand immunoglobulin (rPSGL-Ig), a glycoprotein that binds to P-selectin and inhibits neutrophil adhesion, to protect against I/R injury in an ex vivo rat liver model. METHODS: Rat livers were harvested and stored for 6 hr at 4 degrees C in University of Wisconsin solution and then perfused with oxygenated whole blood for 2 hr. Three groups were studied (n=6 rats/group): an untreated control group; a group that received 0.4 mg/kg rPSGL-Ig intraportally at the time of harvest; and a group that received 0.4 mg/kg rPSGL-Ig plus 1 micromol D-Exo intraportally both at the time of harvest and at the onset of reperfusion. Liver portal venous blood flow was assessed during perfusion, and at the end of each experiment, liver samples were collected for blinded histological evaluation and biochemical analyses. RESULTS: Livers treated with D-Exo + rPSGL-Ig had significantly higher blood flow than livers treated with rPSGL-1Ig alone (P<0.05), and both treatment groups had higher blood flow than controls (P<0.001). Production of carbonyl proteins, a protein oxidation product, was significantly reduced in the D-Exo + rPSGL-1Ig group (P<0.02 vs. controls), but not in the rPSGL-Ig alone group. Total reduced glutathione was significantly higher than controls in the D-Exo + rPSGL-Ig group (P<0.001 vs. controls), but not in the rPSGL-Ig alone group, indicating less oxidative stress in the D-Exo-treated group. Production of malondialdehyde, an index of lipid peroxidation, was significantly less than controls in both treatment groups (P<0.03). Histopathological findings paralleled these results with Banffs scores of 3.3+/-0.5, 1.8+/-0.4, and 1.3+/-0.5 in the control, rPSGL-Ig alone, and D-Exo plus rPSGL-Ig groups, resp. CONCLUSION: rPSGL-Ig provides partial protection against I/R injury to ex vivo rat livers; however, the addition of D-Exo substantially increases protection by reducing oxidative injury. These findings may have clinical relevance in preventing the consequences of I/R injury after liver transplantation.

Animals↗
PubMed2001

Elemental release from dental casting alloys into biological media with and without protein.

OBJECTIVE: The objective of this study was to determine the role of proteins in affecting elemental release from a variety of clinically available dental casting alloys. An important role for proteins was suspected based on previous reports about the corrosion of stainless steel and the cytotoxicity of alloys after exposure to a saline-protein solution. METHODS: Clinically available alloys with compositions ranging from 0 to 94at.% noble elements were exposed for 1 week to either saline, saline with 3% bovine serum albumin (BSA), or complete cell-culture medium with 3% serum. Atomic absorption spectrophotometry was used to measure the release of elements from the alloys. Elemental release was normalized for the exposed surface area of the alloys. RESULTS: In general, more elemental release occurred into the saline-BSA solution compared to saline alone for all released elements (Ag, Cu, Pd, and Zn) except for Ni. Ni release from the NiCr alloy was lower in the presence of BSA. Each element responded somewhat differently with Pd being the least predictable in its behavior. Elemental release was less in the cell-culture medium than in the saline-BSA solution for most elements. For alloys which released multiple elements, all elements responded similarly but not identically to the presence of protein. A high elemental release during exposure to the saline-BSA solution correlated with a low alloy cytotoxicity post-exposure to the saline-BSA. SIGNIFICANCE: This study demonstrates the importance of defining exactly the composition of biological solutions used to assess in vitro corrosion and biocompatibility of dental casting alloys. Other molecules in addition to proteins appeared to be critical to the corrosion of these alloys in vitro.

Analysis of Variance↗
PubMed2001

Examination of the implant-abutment interface after fatigue testing.

PURPOSE: This study examined potential differences in detorque values of abutment screws after fatigue testing when the dimensions between external implant hexagon and internal abutment hexagon were altered or the implant external hexagonal shape was eliminated. MATERIAL AND METHODS: Three subsets (N = 10) of NobelBiocare implants were assessed: (1) standard external hexagon (R), (2) modified hexagon (M), and (3) circular (C) platform geometry. Thirty Procera machined abutments with 25-degree angulated loading platforms were manufactured. Abutments were retained with gold Unigrip abutment screws tightened to 32 N/cm with an electronic torque controller. Vertical scribes across the implant-abutment interface allowed longitudinal displacement evaluation. A carousel-type fatigue testing device delivered dynamic loading forces between 20 and 200 N for 5,000,000 cycles, or the approximate equivalent of 5 years in vivo mastication, through a piston to the abutment platform. Macroscopic and radiographic examination of the implant/abutment specimens was performed. The abutment screws were removed and the detorque values recorded. Bearing surfaces were examined microscopically. RESULTS: No abutment looseness or longitudinal displacements at the implant-abutment interface were noted. Radiographic examination demonstrated no indication of screw bending or displacement. The mean detorque values for R, M, and C were 14.40 +/- 1.84 N/cm, 14.70 +/- 1.89 N/cm, and 16.40 +/- 2.17 N/cm, respectively. The analysis of variance demonstrated significant differences between only designs R and C (P=.031). CONCLUSION: Increasing the vertical height, or degree of fit tolerance, between the implant external hexagon and the abutment internal hexagon or completely eliminating the implant external hexagon did not produce a significant effect on the detorque values of the abutment screws after 5,000,000 cycles in fatigue testing, or the equivalent of 5 years' of mastication for the implant/abutment specimens evaluated.

Analysis of Variance↗
PubMed2001

In vitro TNF-alpha release from THP-1 monocytes in response to dental casting alloys exposed to lipopolysaccharide.

STATEMENT OF PROBLEM: Studies have found that lipopolysaccharide (LPS) attaches to and is eluted from dental alloys, but the biologic effects of LPS are not known. PURPOSE: This study evaluated the ability of dental casting alloys pre-exposed to LPS to activate human monocytes with and without subsequent elution of the LPS. MATERIAL AND METHODS: Eight types of casting alloys (n = 6 specimens per type) were exposed to LPS (Escherichia coli @ 100 micrograms/mL) for 24 hours. Controls were not exposed to LPS. Teflon (Tf) (+/- LPS) served as the material control. Treated alloys were transferred to THP-1 human monocytes for 24 hours or placed into phosphate-buffered saline (PBS) solution for 120 hours before monocyte exposure. Monocyte activation was assessed by tumor necrosis factor alpha (TNF-alpha) secretion into the medium. Alloys without LPS, with LPS but without PBS elution, and with LPS and elution were compared with ANOVA and Turkey intervals (alpha=.05). RESULTS: Specimens without LPS exposure but with elution caused no detectable TNF-alpha secretion from monocytes. Specimens without elution into PBS caused low-to-moderate TNF-alpha secretion, indicating a possible false-positive result from the alloy conditioning solution used. After LPS exposure but no elution, high levels of TNF-alpha were found. When alloys were eluted for 120 hours after LPS exposure, there was no detectable TNF-alpha released. CONCLUSION: In this in vitro system as in past studies, LPS appeared to adhere to and elute from the alloys. Monocytes were activated initially but not after elution into PBS for 120 hours. Alloy conditioning solutions may also have an artifactual effect on cytokine release.

Analysis of Variance↗
PubMed2001

2000 Judson C. Hickey Scientific Writing Award. Effect of impression materials on hybridized dentin.

STATEMENT OF PROBLEM: Tooth sensitivity after crown preparation is not an uncommon complication. For dentin bonding agents to be effective in preventing postoperative sensitivity, they must remain intact throughout the fixed prosthodontic procedures. PURPOSE: This study evaluated, by analyzing the change in dentin permeability, whether a dentin bonding agent was removed from the surface of prepared teeth in the process of making an impression. MATERIAL AND METHODS: Eighty extracted human molars were cut horizontally apical to the cemento-enamel junction and horizontally through the middle of the clinical crown. The specimens were prepared to measure dentin permeability (fluid flow rate, Lp). The specimens (n = 40) were randomly assigned to either the primer-only group (PO) or the primer + adhesive group (PA). Five different impression materials were tested: vinyl polysiloxane, polyether, polysulfide, irreversible hydrocolloid, and reversible hydrocolloid. Dentinal permeability was measured after smear layer removal (control, etched Lp = ELp), after coating the dentin with either PO or PA (coated Lp = CLp), and again after making an impression (impression Lp = ILp). A 1-way ANOVA of differences, followed by a Student-Newman-Keuls test (alpha=.05), was performed to compare the ELp, CLp, and ILp values. RESULTS: A statistically significant difference was found between the CLp and ELp for all 5 impression materials in both groups (PO and PA). No difference was found between the CLp and ILp values for any of the impression materials. No significant differences were found between any of the 5 impression materials or either of the dentin surface treatments (PO or PA) when measuring the CLp and ILp. CONCLUSION: The dentin bonding agent had a significant effect in decreasing the Lp of the treated specimens. None of the impression materials significantly affected the measured CLp. There was no significant difference between the PO or PA (CLp) values.

Acid Etching, Dental↗
PubMed2001

The effect of storage time on the accuracy and dimensional stability of reversible hydrocolloid impression material.

STATEMENT OF PROBLEM: It has been stated that reversible hydrocolloid impression material must be poured immediately to remain accurate. This may not be true with modern formulations of reversible hydrocolloid. The accuracy of the impression, if kept at 100% humidity for varying periods, may not be affected as critically as has been suspected. PURPOSE: The purpose of this study was to evaluate the effect of storage time in a 100% humidity environment on the accuracy of gypsum casts poured from a newer formulation of reversible hydrocolloid impressions. MATERIAL AND METHODS: With the use of a stainless steel master model, 5 standardized reversible hydrocolloid impressions were made for each time interval tested (n = 5). Impressions were made with the use of both Cartiloid blue syringe and Slate tray reversible hydrocolloid material (both manufactured by Van R) to simulate a common clinical protocol. Six groups, representing times at 0, 30, 60, 120, 180, and 210 minutes, were evaluated for a total of 30 specimens. Gypsum casts were measured with a traveling microscope, and dimensional changes were compared between groups with ANOVA and Tukey intervals (alpha=.05). RESULTS: Measurements made up to and including the 60-minute storage time showed clinically acceptable distortion levels. These measurements were similar to the metal model and the gypsum casts poured at time 0 minutes. The only statistically significant difference between the gypsum cast and the metal master model was the distance between abutments at storage time 180 minutes (master model = 30.04 mm [SD 0.001]; gypsum casts = 29.944 mm [SD 0.076]). This difference was -91 microm (P=.002). In general, the gypsum abutments became wider and shorter with time. There was no significant difference between any gypsum abutment in regard to width or height when compared with the metal master model for all the storage times tested. However, as time increased, measurement became harder to accomplish, leading to a larger standard deviation and less reliable results. The distance between abutments remained relatively constant for storage times up to and including 60 minutes. For times longer than 60 minutes, the distance between abutments was reduced and more difficult to read. The distance between abutments at the 3-hour storage time was significantly different than the metal standard and time 0 gypsum casts. CONCLUSION: If a discrepancy of 78 microm (twice the 39 microm single margin opening) is clinically acceptable, then the results of this study show that this type of reversible hydrocolloid can be stored in 100% humidity for at least 60 minutes.

Analysis of Variance↗
PubMed1999

Accelerated toxicity testing of casting alloys and reduction of intraoral release of elements.

STATEMENT OF PROBLEM: Short-term (72-168 hours) in vitro testing of dental casting alloys for cytotoxicity may not reflect in vivo biocompatibility. An accelerated test for evaluation of dental casting alloy cytotoxicity could help screen newly developed alloys more rapidly and accurately. PURPOSE: This study evaluated a method of accelerating alloy cytotoxicity by short-term conditioning of alloys. Cytotoxicity and mass release of these conditioned alloys were compared with alloys conditioned for 10 months or unconditioned alloys. The hypothesis was that a short-term conditioning procedure could be developed that would give cytotoxicity and mass release values similar to alloys exposed to a biologic solution for 10 months. MATERIAL AND METHODS: Dental casting alloys were conditioned in either saline, cell-culture medium, or a saline/bovine serum albumin (BSA) solution for 168 hours before standard in vitro cytotoxicity testing. Eight types of casting alloys with a range of nobilities (98% to 0%) were tested (n = 6). Controls were Teflon (Tf). Conditioned alloys were placed in direct contact with Balb/c fibroblasts for 72 hours, and cell viability was measured by succinic dehydrogenase activity (MTT method) relative to Tf controls. Elements released into the conditioning solutions were measured by atomic absorption spectroscopy. The cytotoxicities of conditioned alloys and total mass released were compared with unconditioned alloys (0 month) and alloys that were exposed to cell culture medium for 10 months. ANOVA and Tukey multiple comparison intervals (alpha =. 05) were used to compare mass released and cytotoxicity. RESULTS: Conditioning for 168 hours altered the cytotoxicity of the alloys. The saline/BSA conditioning solution reduced cytotoxicity of the alloys compared with unconditioned alloys, except for the Ni-Cr alloy. Other conditioning solutions were not as uniform in their effects, some increasing toxicity, others decreasing it. Overall, the saline/BSA solution was the most effective at changing alloy cytotoxicity from the unconditioned (0 month) toward the 10-month values. Mass loss during saline/BSA conditioning most closely approximated 10-month loss for most alloys. CONCLUSION: Conditioning of casting alloys appeared to be a useful method for predicting long-term cytotoxicity with a short-term in vitro test, but all conditioning solutions were not equivalent.

Animals↗
PubMed1999

Cytotoxicity of dental casting alloys pretreated with biologic solutions.

STATEMENT OF PROBLEM: Short-term (72-168 hours) in vitro tests are used to evaluate the cytotoxicity of dental casting alloys. The ability of these short-term tests to predict long-term in vivo cytotoxicity has been questioned. A procedure to accelerate the testing of casting alloys would be useful in predicting longer-term alloy cytotoxicity. PURPOSE: This study hypothesized that preconditioning casting alloys by soaking in a biologic liquid would change subsequent cytotoxicity by removing some elements. Preconditioning may be 1 method of accelerating short-term in vitro tests. MATERIAL AND METHODS: Dental casting alloys were exposed to either saline, cell culture medium, or a saline/bovine serum albumin (BSA) solution for 72 hours before standard in vitro cytotoxicity testing. Six types of alloys were tested (n = 6): 5 Au-Ag-Cu-Pd alloys (single phase) and 1 Ag-Pd-Cu alloy (multiple phase). Teflon (Tf) samples served as a control. After preconditioning, alloys were placed in direct contact with Balb/c fibroblasts for 72 hours, after which cell viability was measured by succinic dehydrogenase activity (MTT method) relative to Tf controls (100% = no toxicity). Elements released into the preconditioning solutions were measured by atomic absorption spectroscopy. Cytotoxicities of preconditioned alloys and amounts of elemental release were compared with unconditioned alloys. RESULTS: A preconditioning time of 72 hours was sufficient to change the cytotoxicity of the tested alloys. The alloys that were more cytotoxic initially became less cytotoxic after preconditioning. For all the alloys tested, except the Ag-Pd-Cu multiphase alloy, preconditioning with either the saline or the saline/BSA solution caused an increase in cellular activity, therefore the preconditioned alloys were less cytotoxic. The cell culture medium preconditioning solution had a variable effect, causing increased or decreased cellular activity depending on the alloy treated. CONCLUSION: Preconditioning of casting alloys decreased subsequent cytotoxicity. However, not all preconditioning solutions are equivalent. A preconditioning strategy may be useful in accelerating the short-term cytotoxicity test toward a longer-term result.

3T3 Cells↗
PubMed1999

In vitro cytotoxicity of dental casting alloys over 8 months.

Although in vitro cytotoxicity tests have been a valuable part of the biological testing of dental casting alloys, these tests are generally limited by their short-term nature ( < 168 h). The objective of the current study was to measure the in vitro cytotoxicity of representative types of dental casting alloys over a relatively long-term interval (months) and compare longer-term cytotoxicity with that seen initially. Polished casting alloy samples were exposed to cell-culture medium for 30-day intervals. During the last 3 days of each interval, the medium was changed to provide a 3-day extract which was then placed on fibroblast or macrophage cultures for 48 h. The mitochondrial activity of the cells was measured and compared to control cultures to assess the cytotoxic effect of the alloys. The cytotoxic effect was plotted versus time of medium exposure. The total time of exposure was 8 months. For most alloys, the mitochondrial response was constant over the 8 months, indicating that the cytotoxic effect of the alloys did not change significantly after extended exposure to the medium. A trend of improving biological response was suspect for a reduced-gold alloy, but this trend was not statistically significant. The mitochondrial activity of the macrophages was less sensitive to the alloy extracts than the activity of the fibroblasts, which was significantly suppressed for several alloy types. However, mitochondrial activity of the macrophages was significantly increased for several alloys in the early time intervals. The total noble metal content of the alloys was not necessarily predictive of the biological response. Thus, it appears that in this indirect test of in vitro cytotoxicity, the short-term cytotoxicity is predictive of the longer-term for many types of dental casting alloys.

Analysis of Variance↗
PubMed1999

Initial versus subsequent release of elements from dental casting alloys.

The release of elements from dental casting alloys is directly related to adverse biological effects they may have. Longer-term (>1 month) studies of elemental release have suggested that release decreases significantly after a higher initial release of elements. The aim of the current study was to measure the release of elements from a variety of clinically relevant dental casting alloys and compare the release at weekly intervals through 4 weeks. The hypothesis was that the release during the initial week should be higher than in subsequent weeks, and that cytotoxicity should decrease as elemental release decreases. Alloy samples were exposed to cell-culture medium which was changed at weekly intervals and assessed for elemental release by means of atomic absorption spectrometry. The cytotoxicity of the medium was also measured. The results showed that for single phase alloys, initial release was often significantly higher in the first weeks than in subsequent weeks, but not for all elements in an alloy. Multiple phase alloys showed steady or increasing release relative to the first week. Cytotoxicity relationships were complex depending on which elements were released and the ratios of elements released. This study suggests that short-term tests (<1 week) may not be appropriate to evaluate longer-term elemental release or cytotoxicity because of changing rates of elemental release.

Animals↗
PubMed1999

Clinical study of tooth shade lightening from dentist-supervised, patient-applied treatment with two 10% carbamide peroxide gels.

PURPOSE: Prescribed, patient-applied tooth lightening agents, or nightguard vital bleaching, typically utilizes a 10% carbamide peroxide agent applied during nocturnal hours. The purpose of this randomized double-blind study was to compare the amount of tooth color change in two groups of subjects using dentist-supervised, patient-applied 10% carbamide peroxide gel. MATERIALS AND METHODS: One group used Opalescence (Ultradent Products Inc., South Jordan, Utah) and the other NiteWhite Excel (Discus Dental, Inc., Los Angeles, California). Evaluation of tooth color for the six maxillary anterior teeth was done using a Vita shade guide at baseline, 1, 2, and 4 weeks. Subjects were instructed to apply the gel nocturnally using a custom-made soft tray 8 hours per day for 2 weeks. The 16 tabs of the shade guide were ranked according to value from darkest to lightest. The number (1-16) that correlated to the shade tab selected as the match for each tooth was the outcome variable. A Kruskal-Wallis one way analysis of variance on ranks was used. RESULTS: The test revealed no statistically significant difference between Opalescence and NiteWhite Excel for lightening the teeth (p = .807). The color change was still significant after 2 weeks without further bleaching activity. The baseline evaluation of the maxillary incisors and canines for all subjects, regardless of group, demonstrated a significant shade difference, with the canines being darker. This difference was not seen after 2 weeks of active bleaching or at the 4-week evaluation. CLINICAL SIGNIFICANCE: In this study comparing bleaching products, patients using Opalescence and NiteWhite Excel experienced a significant change in the color of their teeth relative to baseline values after 2 weeks of active treatment.

Adult↗
PubMed1997

Burning mouth syndrome: a review of etiologies.

STATEMENT OF PROBLEM: Dental practitioners occasionally have patients present clinically with a history of chief complaint of burning and painful sensations in the oral cavity. Often the patient demonstrates clinically normal mucosa, which can make formulating a diagnosis challenging. This scenario, has been referred to as burning mouth syndrome, a multifactorial syndrome. PURPOSE: The purpose of this article is to present a review of etiologic factors and clinical implications related to the condition of burning mouth syndrome.

Adult↗
PubMed1997

Lipopolysaccharide affinity for titanium implant biomaterials.

STATEMENT OF PROBLEM: Lipopolysaccharide (LPS) affinity for titanium implant biomaterials could affect crevicular LPS concentrations and thereby influence periimplant inflammation. PURPOSE OF STUDY: The purpose of this study was to evaluate Porphyromonas gingivalis and Escherichia coli LPS affinity for titanium biomaterials groups that differed in surface oxide composition and surface roughness. MATERIAL AND METHOD: Polished and abraded grade 1 commercially pure titanium and grade 5 alloyed extra low interstitial titanium specimens were treated with 10 EU/mm2 and radiolabeled LPS. RESULTS: The resultant mean +/- SD LPS adherence values ranged from 4.17 +/- 0.29 to 4.79 +/- 0.40 EU/ mm2. No difference in adherence and elution was indicated on the basis of LPS type, surface oxide composition, or surface roughness. Moreover, P. gingivalis and F. coli LPS desorption was below detection. CONCLUSION: Clinically, the high affinity of both LPS types for titanium biomaterials may adversely influence the periimplant tissue response.

Adsorption↗
PubMed1997

Effect of glutaraldehyde cold sterilants on light transmission of curing tips.

This research examined the effect of immersion in glutaraldehyde-based cold sterilizing solutions on the ability of light-curing tips to transmit a standardized light intensity. Five commercial cold sterilizing solutions were selected, based on their classification: neutral (Cetylcide-G, 3.2%), acidic (Banicide, 2.0%), or alkaline (Cidex Plus, 2.5%; Cidex 7, 3.4%; and Sporicidin, 0.5%). Distilled water was used as the control. The light intensity transmitted through 24, 8-mm-diameter curing tips of similar type was determined by applying a standardized intensity (500 m W/cm2). Three tips were placed into each type of solution. The percentage of preimmersion intensity was determined at periodic intervals until all tips had received a total of 1,000 hours of immersion. After 1,000 hours' immersion, light transmission decreased significantly more in tips subjected to Cidex 7 than in tips subjected to all other treatments, which were all equivalent to the water control (an average increase of 1.5% over preimmersion values). The decrease in intensity seen with Cidex 7 averaged 49% and could not be totally recovered after use of conventional tip-polishing methods. Reduction in light levels could not be correlated with the pH of the sterilizing solutions.

Cold Temperature↗
PubMed1995

Leukemia inhibitory factor and tumor necrosis factor induce manganese superoxide dismutase and protect rabbit hearts from reperfusion injury.

Leukemia inhibitory factor (LIF) and tumor necrosis factor (TNF) have been shown to protect animals from radiation, hyperoxia, and endotoxic shock. TNF is also known to induce the expression of manganese superoxide dismutase (MnSOD) in vitro and in vivo. We therefore examined the effects of these cytokines on reperfusion injury in the isolated rabbit heart model. Rabbits were injected intravenously with 10 micrograms of either human TNF-alpha or lymphotoxin (TNF-beta), or murine TNF-alpha or murine LIF dissolved in saline. Control animals were injected with an equal volume of saline. After 24 h, hearts were isolated and perfused. Following an equilibration period, the hearts were subjected to 1 h ischemia and 1 h of reperfusion. All treated groups showed significant increases in percent recovery of developed tension (% preischemic) when compared to saline-treated control hearts. In addition there were significant decreases in lactate dehydrogenase release (LDH), accumulation of thiobarbituric acid reactive substances (TBARS), and accumulation of carbonyl proteins. These results correlate with increases in myocardial MnSOD activity. Thus, the protection from myocardial reperfusion injury seen in the pretreated group may be due to a mechanism that involves the induction of MnSOD.

Analysis of Variance↗
PubMed1995

Mitochondrial respiration scavenges extramitochondrial superoxide anion via a nonenzymatic mechanism.

We determined that mitochondrial respiration reduced cytosolic oxidant stress in vivo and scavenged extramitochondrial superoxide anion (O2-.) in vitro. First, Saccharomyces cerevisiae deficient in both the cytosolic antioxidant cupro-zinc superoxide dismutase (Cu,Zn-SOD) and electron transport (Rho0 state) grew poorly (P < 0.05) in 21% O2 compared with parent yeast and yeast deficient only in electron transport or Cu,Zn-SOD, whereas anaerobic growth was the same (P > 0.05) in all yeast. Second, isolated yeast and mammalian mitochondria scavenged extramitochondrial O2-. generated by xanthine/xanthine oxidase. Yeast mitochondria scavenged 42% more (P < 0.05) extramitochondrial O2-. during pyruvate/malate-induced respiration than in the resting state. Addition of either antimycin (respiratory chain inhibitor) or FCCP (respiratory chain uncoupler) prevented increased O2-. scavenging. Mitochondria isolated from yeast deficient in the mitochondrial manganous superoxide dismutase (Mn-SOD) increased (P < 0.05) O2-. scavenging 56% during respiration. This apparent SOD activity, expressed in units of SOD activity per milligram of mitochondrial protein, was the same (9 +/- 0.6 vs. 10 +/- 1.0; P = 0.43) as the O2-. scavenging of mitochondria with Mn-SOD, suggesting that respiration-dependent mitochondrial O2-. scavenging was nonenzymatic. Finally, isolated rat liver and lung mitochondria also increased (P < 0.05) O2-. scavenging during respiration. We speculate that respiring mitochondria, via the protonmotive pump, present a polarized, proton-rich surface that enhances nonenzymatic dismutation of extramitochondrial O2-. and that this is a previously unrecognized function of mitochondrial respiration with potential physiological ramifications.

Animals↗
PubMed1994

The toxicity of high-dose superoxide dismutase suggests that superoxide can both initiate and terminate lipid peroxidation in the reperfused heart.

Recently, we described an anomalous bell-shaped dose-response curve for the protection of the reoxygenated isolated myocardium by superoxide dismutase (SOD). SOD is dramatically protective up to a point (5 micrograms/ml in the perfusate) beyond which it loses its ability to protect and, at very high doses (50 micrograms/ml), exacerbates the injury. We proposed that O2-. may serve as both initiator and terminator of lipid peroxidation, such that over scavenging the radical may increase net lipid peroxidation via increased chain length. We examined the ability of U74389F, a lipid peroxidation inhibitor, to ameliorate the toxicity of high-dose SOD in the isolated perfused rabbit heart preparation. The results show a significant improvement in the percent recovery of developed tension of hearts treated with U74389F and overdosed with MnSOD, as well as a decrease in thiobarbituric acid reactive substances.

Animals↗