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Biomedical subjects

J Kalra

Publications and source records attributed to J Kalra.

At least 55 records · Page 3Linked to original sources

A critical review of the neurotoxicity of styrene in humans.

Styrene monomer is an aromatic industrial solvent. It is used to make polystyrene, resins, rubber, reinforced material and boats. Humans are exposed to styrene in occupational situations mostly during spraying processes at work, most of which is inhaled. The major neurotoxic effects of styrene as reviewed are prenarcotic effects, electroencephalographic abnormalities, slowing of motor, sensory and distribution nerve conduction velocities that reveal the possibility of polyneuropathy, dysfunction of the autonomic nervous system, slowing of reaction times, and centrally-controlled otoneurotoxicity. In acute exposure situations reversal of adverse effects has been observed; however, the impact of long-term exposure needs further studies. Dopamine depletion has been reported as a neurochemical basis of the neurotoxicity of styrene. Styrene epoxide, a toxic intermediate metabolite, has also been reported to deplete glutathione and cause lipid peroxidation, possibly leading to neuronal membrane damage. Raised concentrations of glial fibrillary acidic protein has been reported as an indicator of neurotoxicity in rats, which may damage the brain through astrogliosis phenomenon. This damage is also correlated to the toxic effects of styrene epoxide. Recently decreased monoamine oxidase type B activity in peripheral blood cells has been investigated as biochemical indicator of neurotoxicity of styrene in workers. There is a need for long-term studies, consideration of confounding factors (smoking, alcohol, diet, drugs, working environment and exposure to other solvents), and the effects on different ethnic and racial groups. More electroencephalographic studies and computer tomographic investigations are desired. Further reduction of the exposure limit to below 50 ppm is recommended.

Animals↗

Detection of ischemia-reperfusion cardiac injury by cardiac muscle chemiluminescence.

Various methods have been used in the past to assess the implication of oxygen free radicals (OFR) in ischemia-reperfusion-induced cardiac injury. Luminol-enhanced tert-butyl-initiated chemiluminescence in cardiac tissue reflects oxidative stress and is a very sensitive method. It was used to elucidate the role of OFR in cardiac injury due to ischemia and reperfusion. Studies were conducted on perfused isolated rabbit hearts in three groups (n = 8 in each): I, control; II, submitted to global ischemia for 30 min; III, submitted to ischemia for 30 min followed by reperfusion for 60 min. The heart tissue was then assayed for chemiluminescence (CL); content of malondialdehyde (MDA), an indicator of OFR-induced cardiac injury; and activity of tissue levels of antioxidants [superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px)]. The control values for left and right ventricular CL and malondialdehyde were 81.1 +/- 15.4 (S.E.) and 182.4 +/- 50.3 (S.E.), mv.min.mg protein-1; and 0.024 +/- 0.006 (S.E.) and 0.324 +/- 0.005 (S.E.) nmoles.mg protein-1 respectively. Ischemia produced an increase in the cardiac CL (3.3 to 4.4 fold) and MDA content (2 to 2.6 fold). Reperfusion following ischemia also produced similar changes in CL and MDA content. The control values for activity of left ventricular SOD, catalase, and GSH-Px were 45.77 +/- 1.73 (S.E.) U.mg protein-1, 5.35 +/- 0.51 (S.E.) K.10(-3).sec-1.mg protein-1, and 77.50 +/- 7.70 (S.E.) nmoles NADPH.min-1.mg protein-1 respectively. Activities of SOD and catalase decreased during ischemia but were similar to control values in ischemic-reperfused hearts. The GSH-Px activity of left ventricle was unaffected by ischemia, and ischemia-reperfusion. GSH-Px activity of the right ventricle increased with ischemia, and ischemic-reperfusion. These results indicate that cardiac tissue chemiluminescence would be a useful and sensitive tool for the detection of oxygen free radical-induced cardiac injury.

Animals↗

Gamma-vinyl GABA prevents hippocampal and substantia nigra reticulata damage in repetitive transient forebrain ischemia.

GABAergic inhibitory mechanisms may offer protection to neurons after global ischemia. We tested the effects of gamma-vinyl GABA, a GABA-transaminase inhibitor, via continuous infusion in the third ventricle (Alza pumps) in a gerbil model of repetitive forebrain ischemia. We used two episodes of 3 min duration with a 'reperfusion' interval of 1 h between the insults. Histological analysis was done with silver staining 5 days after the insult. Our results show that there is significant protection of the hippocampus CA1 region and substantia nigra reticulata in treated animals compared to controls. An increase in GABA levels, decrease in glutamate, or mild hypothermia, may be potential mechanisms for this protection. GABAergic agents may prove useful agents in repetitive ischemia.

4-Aminobutyrate Transaminase↗

Novel bovine heart calmodulin-dependent protein kinase which phosphorylates a high molecular weight calmodulin-binding protein.

A novel calmodulin-dependent protein kinase has been isolated from bovine cardiac muscle by successive chromatography on DEAE-Sepharose 6B, Calmodulin-Sepharose 4B affinity and Sepharose 6B chromatography columns. The protein kinase was shown by gel filtration chromatography to have a molecular mass of 36,000 daltons. The highly purified protein kinase stoichiometrically phosphorylated the high molecular weight calmodulin-binding protein from cardiac muscle [Sharma RK (1990) J Biol Chem 265, 1152-1157] in a Ca2+/calmodulin-dependent manner. The phosphorylation resulted in the maximal incorporation of 1 mol of phosphate/mol of the high molecular weight calmodulin-binding protein. Other Ca2+/calmodulin-dependent protein kinases failed to phosphorylate the high molecular weight calmodulin-binding protein. The distinct substrate specificity of this protein kinase indicates that it is not related to the known calmodulin-dependent protein kinases and therefore constitutes a novel protein kinase.

Animals↗

Oxygen free radical producing activity of polymorphonuclear leukocytes in patients with Parkinson's disease.

Oxygen free radicals (OFRs) have been suggested in the pathogenesis of Parkinson's disease (PD). These free radicals exert their cytotoxic effect by peroxidation of lipid membrane resulting in the formation of malondialdehyde (MDA). Polymorphonuclear (PMN) leukocyte is one of the major sources of OFR. However, the oxygen free radical producing activity of PMN leukocytes in patients with PD is not known. We therefore studied the oxygen free radical producing activity of polymorphonuclear leukocytes and MDA levels in the serum of healthy subjects and in patients with Parkinson's disease. The oxygen free radical producing activity of PMN leukocytes in blood and the MDA content in serum were significantly higher in patients with Parkinson's disease than in healthy subjects. These results indicate a possible role of oxygen free radicals in the pathogenesis of Parkinson's disease.

Aged↗

Serum antioxidant enzyme activity in Parkinson's disease.

The activities of superoxide dismutase (SOD; EC 1.15.1.1) and glutathione peroxidase (GSHPx; EC 1.11.1.9), the enzymes that metabolize the superoxide anion and hydrogen peroxide, respectively, were measured in serum from healthy subjects and patients with Parkinson's disease (PD). The activities of SOD and GSHPx in patients with PD were higher than those in normal healthy individuals. These results suggest that the increased activities of these enzymes could be due to oxidative stress in the initial stages of this disease.

Aged↗

Repetitive transient forebrain ischemia in gerbils: delayed neuronal damage in the substantia nigra reticulata.

Repetitive cerebral ischemia results in severe neuronal damage in multiple regions of the brain including the hippocampus, striatum, thalamus, medial geniculate nucleus and the substantia nigra reticulata (SNr). We postulated that the damage in the SNr was delayed, resulting from a loss of striatal inhibitory input. We used the gerbil model of repetitive ischemia (3 min times 2 and 3 min times 3) to evaluate the extent of neuronal damage at 2, 3, 5 and 7 days after the ischemic insult. Silver degeneration stain was used for histological evaluation. Our results indicate that damage in the SNr begins after 48 h and is maximum at 7 days. This delay in onset of damage offers a window for pharmacological protection.

Animals↗

Oxygen free radicals in volume overload heart failure.

It has been suggested that oxygen free radicals (OFR) depress the excitation-contraction coupling in cardiac muscle. It is possible that a decrease in the cardiac contractility in the failing heart may be due to an increased OFR producing activity of polymorphonuclear (PMN) leukocytes. We studied the OFR producing activity (chemiluminescence) of PMN leukocytes from blood in dogs with heart failure due to chronic volume overload. The animals were divided into two groups: I) normal, (n = 10): II) dogs with mitral insufficiency (MI) of 6 to 9 months duration, (n = 10). Hemodynamic studies were done to establish the presence of heart failure. Blood samples were collected to measure PMN leukocyte chemiluminescence. There was a decrease in the cardiac index and index of myocardial contractility (dp/dt/IIP) and an increase in the left ventricular end-diastolic pressure in dogs with MI indicating left ventricular failure. The peak chemiluminescent activity of the PMN leukocytes in blood of dogs with failure was about four folds greater than that in the blood from normal dogs. These results suggest that there may be an increased OFR generation in dogs with volume overload heart failure. The decrease in the myocardial contractility in the failing heart might be due to an increase in the OFR produced by the PMN leukocytes.

Animals↗

Increased oxygen free radical activity in patients on cardiopulmonary bypass undergoing aortocoronary bypass surgery.

Cardiac dysfunction after cardiopulmonary bypass (CPB) has been reported by various investigators. Oxygen free radicals have been shown to depress cardiac function and contractility. To evaluate the possible role of oxygen free radicals (OFR) in post-pump cardiac dysfunction, measurements of cardiac function, OFR producing activity of polymorphonuclear (PMN) leukocytes (PMN chemiluminescence) and malondialdehyde (MDA), a lipid peroxidation product, in blood were made at induction of anesthesia (T1), before cross clamping of the aorta (T2), after closure of the chest (T3), and 24 hours postoperatively (T4) in 21 patients undergoing aortocoronary bypass surgery. The total OFR-derived chemiluminescence at T1, T2, T3, and T4 was 1590 +/- 156, 3169 +/- 338, 1972 +/- 214, and 2614 +/- 366 mv.min.10(6) PMN-1, respectively. Superoxide dismutase (SOD)-inhibitable chemiluminescence at T1, T2, T3, and T4 was 1214 +/- 129, 2674 +/- 328, 1752 +/- 215, and 2139 +/- 292 mv.min.10(6) PMN-1, respectively. Superoxide anion at T1, T2, T3, and T4 was 0.99 +/- 0.14, 1.30 +/- 0.17, 1.07 +/- 0.14, and 1.19 +/- 0.12 nmol.10(6) PMN-1.30 min-1, respectively. Blood MDA at T1, T2, T3, and T4 was 0.17 +/- 0.02, 0.25 +/- 0.03, 0.20 +/- 0.03, and 0.23 +/- 0.02 nmol/ml, respectively. OFR-derived and SOD inhibitable chemiluminescence, superoxide anion, and blood MDA increased significantly during CPB and postoperatively. There were decreases in the blood pressure and stroke volume, and increases in the central venous pressure, capillary wedge pressure, and heart rate during CPB and postoperatively. Cardiac output remained unchanged during this procedure. There was leukopenia during CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Beneficial effects of methionine on myocardial hemodynamic and cellular functions in hemorrhagic shock.

Hypochlorous acid (HOCl), produced by activated polymorphonuclear (PMN) leukocytes, has been reported to depress cardiac function and contractility. Various mechanisms exist for activation of PMN leukocytes during hemorrhagic shock and reperfusion. In order to determine the role of HOCl in hemorrhagic shock and reinfusion, the authors studied the effects of shock and reinfusion on the cardiac function, contractility, blood lactate, blood gases, and creatine kinase (CK) and MB fraction of CK (MBCK) with and without methionine (quencher of HOCl) in anesthetized dogs. Dogs were divided into two groups: Group I, hemorrhagic shock (two hours) and reinfusion (two hours): Group II, hemorrhagic shock and reinfusion with methionine treatment. Cardiac index, mean arterial pressure, and index of cardiac contractility were similar in the two groups during shock. Postinfusion recovery of cardiac function and contractility was better in group II. Increases in blood lactate were similar in the two groups during shock. The rate of return of blood lactate to preshock values after reinfusion was greater in group II. The increases in serum CK and MBCK of the two groups during shock were similar but not significant. Following reinfusion the levels of these enzymes increased significantly, but the increases in group II were less. These results suggest that HOCl produced by activated PMN leukocytes may play a role in cardiac damage during hemorrhagic shock and reinfusion. Methionine may have beneficial effects in the hemodynamic and metabolic recovery and may reduce cellular damage during hemorrhage shock and reinfusion.

Animals↗

Methionine in protection of hemorrhagic shock: role of oxygen free radicals and hypochlorous acid.

Various mechanisms may exist for activation of polymorphonuclear (PMN) leukocytes during hemorrhagic shock and reinfusion. During activation of PMN leukocytes, hypochlorous acid (HOCl) is produced in addition to oxygen free radicals. We studied the effects of hemorrhagic shock and reinfusion on cardiac function and contractility, oxygen free radical producing activity of PMN leukocytes (PMN chemiluminescence), and serum and cardiac tissue malondialdehyde (MDA), a lipid peroxidation product, with and without methionine (quencher of hypochlorous acid) in anesthetized dogs, in order to assess the role of hypochlorous acid in depression of cardiac function and contractility in hemorrhagic shock. The dogs were divided into two groups: group I, hemorrhagic shock (2 hr) followed by reinfusion (2 hr); and group II, hemorrhagic shock and reinfusion similar to group I but methionine (30 mg/kg i.v.) was administered before bleeding, before reinfusion, and after 1 hr of reinfusion in this group. Mean arterial pressure (mAo), mean pulmonary arterial pressure (mPAP), index of myocardial contractility (dp/dtmax), and cardiac function (stroke volume index [SVI], left-ventricular work index [LVWI]) decreased significantly during shock and the decreases were similar in both groups. The indices of myocardial contractility which are independent of pre- and/or afterload ([dp/dt]/IIP and [dp/dt]/IIP/CPIP) were affected to a lesser degree than the other indices of myocardial contractility (dp/dtmax) during shock and reinfusion. However, the systemic and pulmonary vascular resistance increased significantly in both groups. Postinfusion recovery of cardiac function and contractility in group II was greater than in group I. Cardiac function and contractility after reinfusion returned to preshock levels initially followed by a decrease below the preshock values in group I. However, these parameters remained at or above preshock levels after reinfusion in group II. Cardiac tissue MDA levels were higher in group I, as compared to those in control dogs. The tissue levels of MDA in group II were lower than in group I but similar to those of control. The serum MDA did not change significantly during shock and reinfusion in either group. Although there were increases in the serum MDA after reinfusion in group I, they were not significant. While the chemiluminescent activity of PMN leukocyte increased significantly in group I, this activity decreased significantly in group II during shock and reinfusion. Methionine in in vitro studies did not affect the oxygen free radical producing activity of PMN leukocyte. These results suggest that hypochlorous acid is produced during shock and reinfusion. The decrease in the cardiac function and contractility after reinfusion may be due to hypochlorous acid.

Animals↗

During repetitive forebrain ischemia, post-ischemic hypothermia protects neurons from damage.

In rodents damage from repetitive transient cerebral ischemia is more severe than that seen with a single ischemic insult of similar duration. Mild hypothermia has been shown to be very effective in protecting the brain during single ischemic insults. We tested the protective effects of hypothermia in repetitive ischemic insults. We used the gerbil model of repetitive ischemia (three minutes ischemia repeated at one hourly intervals three times) and histological evaluation was done using the silver staining technique. Our study reveals that a decrease in body and scalp temperature by 1-2 degrees Celsius can significantly reduce neuronal damage in the cerebral cortex, CA1 region of the hippocampus and substantia nigra reticulata during repetitive ischemia. As the hypothermia was induced after the initial insult, we believe this offers an opportunity for intervention in the clinical settings.

Animals↗

Construction and characterization of a high-affinity chimeric anti-colorectal carcinoma antibody ccM4.

We have produced a high-affinity chimeric anti-colorectal carcinoma antibody, ccM4, chimerized in both heavy and light chains by the construction of two expression vectors, the chimeric heavy-chain expression vector mpSV2neo-EP1-Vm4Cr1 and chimeric light-chain vector mpSV2gpt-EP1-VKCK. These vectors contained the neo or gpt gene as a selection marker, the murine immunoglobulin promoter and enhancer (EP1), the genomic DNA fragments of human immunoglobulin constant region (CK and C gamma 1), and murine cDNA fragments of VH and VK region amplified and cloned directly from the B72.3 hybridoma RNA by the polymer chain reaction technique. These two vector DNAs were sequentially transfected into the SP2/0Ag14 cell line. Transfectants were selected in media containing both G418 and mycophenolic acid. The ccM4 antibody was purified from transfectant supernatants with positive binding reactivity for the TAG72 antigen on a protein A column. We demonstrated that ccM4 antibody retained the same high binding reactivity for the TAG72 antigen as its counterpart, the high-affinity chimeric heavy-chain cB72.3m4 antibody. The ccM4 antibody bound specifically to human colon cancer cells, displayed biodistribution patterns similar to cB72.3m4 antibody, and mediated effective antibody-dependent cellular cytotoxicity to human OVCAR3 tumor cells. Therefore, the high-affinity chimeric ccM4 antibody should be useful in cancer immunotherapy.

Animals↗

Cytosine arabinoside and cisplatin for advanced breast cancer. A phase II study of the Cancer and Leukemia Group B.

Forty-four women with advanced breast cancer participated in a prospective clinical trial to evaluate the efficacy and toxicity of a regimen consisting of cytosine arabinoside and cisplatin. All patients had previously received chemotherapy. Three patients (7%) responded to therapy with response durations of 153, 160, and 441 days. The median time to disease progression and median survival time in all 44 patients were 2.3 and 5 months, respectively. This regimen had significant toxicity, with most patients experiencing severe or life-threatening hematologic, renal, or infectious complications. This regimen cannot be recommended for previously treated patients with advanced breast cancer.

Adult↗

Oxygen-derived free radicals producing activity and survival of activated polymorphonuclear leukocytes.

Activation of polymorphonuclear (PMN) leukocytes is known to generate oxygen free radicals (OFR). However the fate of activated PMN leukocytes is not known. We investigated the OFR producing (chemiluminescence) activity and the survival of the activated PMN leukocytes. The study was divided into two groups. Group I, In vivo study (n = 7): zymosan (8.4 mg/kg) was administered intravenously in the anesthetized dogs and the blood samples were collected before and after 5, 15, 30, 60 and 120 min of zymosan administration. This group represents the in vivo pre-stimulated PMN leukocytes; Group II, In vitro study (n = 7): the blood were collected from dogs and further divided into two groups. Group A (n = 7): non-stimulated, without any added zymosan and group B (n = 7): zymosan was added to stimulate PMN leukocytes. Blood samples from group A and B were also collected at various time intervals similar to in vivo studies. Oxygen free radical producing activity of PMN leukocytes was monitored by measuring luminol-dependent chemiluminescence (CL). Opsonized zymosan was used to activate PMN leukocytes. The studies in which the PMN leukocytes were stimulated in in vivo, both oxygen derived free radicals and superoxide dismutase (SOD) inhibitable oxygen free radical CL decreased significantly for 60 min and tended to reach thereafter to the pre-stimulated values. The resting chemiluminescence (chemiluminescence without zymosan stimulation in the assay medium) increased significantly for 15 min reaching to pre-stimulated values at 30 min and thereafter. In in vitro studies, oxygen derived free radicals CL of pre-stimulated PMN leukocytes (Group B) was depressed for the whole duration of investigation while SOD inhibitable CL was depressed for only 60 min. There was approximately a two-fold increase in the resting CL within 5 min of PMN leukocyte activation and it remained high for the whole duration of study. The chemiluminescence of non-stimulated PMN leukocytes in vitro (group A) remained practically normal throughout the period of observation. In in vivo studies, total white blood cells (WBC) and PMN leukocyte counts decreased initially and tended to approach towards pre-stimulated values at the end of the protocol. There were no changes in these counts in in vitro studies. These results indicate that the capacity to generate OFR is decreased in the in vivo and in vitro pre-stimulated PMN leukocytes. However this activity recovers with time. This study also suggests that the activated PMN leukocytes are not destroyed.

Animals↗

Influence of endothelin on cardiovascular function, oxygen free radicals, and blood chemistry.

Endothelin, a peptide that is derived from vascular endothelial cells, is a potent constrictor of mammalian blood vessels in in vitro studies. Various clinical conditions have been reported to be associated with an increase in the blood and tissue levels of endothelin. In the present study, the effects of two doses (2.059 and 4.118 micrograms/kg, intravenously) of endothelin on cardiac function and contractility; blood lactate, gases, and pH levels; blood and cardiac tissue MDA levels; PMN leukocyte chemiluminescence activity; and total WBC and PMN leukocyte counts were investigated in anesthetized dogs. Hemodynamic measurements and collection of blood samples for various biochemical measurements were made before and at various intervals up to 2 hours after endothelin administration. Endothelin in the large dose (4.118 micrograms/kg) produced a prolonged decrease in the indices of cardiac contractility and cardiac function and increases in TSVR, PVR, and mean right atrial pressure. The changes in the hemodynamic parameters with the smaller dose (2.059 micrograms/kg) were similar but of smaller magnitude. Significant decreases in dp/dt at CPIP:PAW and CI and increases in TSVR and PVR were observed with the smaller dose of endothelin. There were decreases in the blood HCO3- and pH levels and an increase in H+ and blood lactate concentration and CK activity with the high dose of endothelin. No changes were observed in blood PO2 and PCO2 with either dose of endothelin. Circulating WBCs and PMN leukocytes decreased significantly with both doses of endothelin. There were no changes in the oxygen free radical-producing activity of PMN leukocytes and in the blood and cardiac tissue MDA levels. These results suggest that endothelin decreased cardiac function and cardiac contractility and increased SVR and PVR. The decrease in cardiac function and contractility may be due to ischemia from constriction of coronary arteries. The hemodynamic changes are unlikely be due to oxygen free radicals since there was no increase in the blood and cardiac tissue MDA levels and no change in the PMN chemiluminescence. These studies suggest that increases in endothelin levels in certain clinical conditions might cause added deleterious effects on cardiovascular function.

Animals↗

Increased production of oxygen free radicals in cigarette smokers.

Oxygen free radicals are known to produce damage in many biological tissues. Cigarette smoking is a major risk factor for various diseases. It is possible that oxygen free radical producing activity of polymorphonuclear (PMN) leucocytes is increased by cigarette smoking. We studied the oxygen free radical producing (luminol-dependent chemiluminescent) activity of PMN leucocytes in blood and the malondialdehyde (lipid peroxidation product) content of blood and serum in nonsmokers and smokers. The zymosan-induced chemiluminescent activity was measured on a LKB 1251 luminometer. The malondialdehyde (MDA) was measured as thiobarbituric acid (TBA) reactive substances. The chemiluminescent activity due to oxygen-derived free radicals (superoxide anion, hydrogen peroxide, hydroxyl radical) and superoxide dismutase (SOD)-inhibitable (superoxide anion) in nonsmokers were 1215.1 +/- 91.1 and 849.3 +/- 72.3 mV min/10(6) PMN leucocytes respectively. There was a significant increase in the oxygen-derived free radicals and SOD-inhibitable chemiluminescence in smokers. The values of blood and serum MDA were 171.7 +/- 6.1 and 222.2 +/- 5.6 nmoles/l respectively in nonsmokers. There was an increase in both blood and serum MDA in smokers. These results suggest that the increased generation of oxygen free radicals by PMN leucocytes might be responsible for an enhanced risk of various diseases related to cigarette smoking.

Adult↗

Effect of oxygen free radicals, hypoxia and pH on the release of liver lysosomal enzymes.

We investigated the effect of acidic environment, hypoxia and oxygen free radicals on the release of beta-glucuronidase from rat liver lysosomes. A lysosomal enriched fraction from the homogenate of rat liver was prepared, using differential centrifugation technique. Exogenous oxygen free radicals were generated using xanthine-xanthine oxidase system. The release of beta-glucuronidase activity was measured from the lysosomes. The lysosomal fraction was exposed to various pH (8.0, 7.4, 6.5, 6.0, 5.5) and pO2 (454, 172, 96, 57,34 mm Hg) separately or to a combination of low pH (5.5, 6.5) and low pO2 (34, 57 mm Hg). The changes in pH or pO2 separately did not cause any increase in the release of beta-glucuronidase activity. The presence of oxygen free radicals at each pH or pO2 resulted in about a 3-fold increase in the release of beta-glucuronidase. A combination of very low pO2 and pH (pO2 (mm Hg)/pH; 34/5.5, 34/6.5) resulted in an increased release of beta-glucuronidase from lysosomes. Oxygen free radicals in the presence of both low pO2 and pH resulted in a further increase in the release of beta-glucuronidase. These data indicate that oxygen free radicals and not the alterations in pH and/or pO2 are primarily responsible for the disruption of lysosomes.

Animals↗