Scintigraphic assessment of renal function in steel plant workers occupationally exposed to lead.

OBJECTIVES: Occupational exposure to lead may produce kidney damage, but existing data on the dose range associated with nephrotoxicity are inconclusive. We here assessed renal function under conditions of low to moderate lead exposure using renal scintigraphy. METHODS: Fifty-three male foundrymen (exposed group) and fourty male office workers (control group) from a steel plant were included in the study. Glomerular and tubular renal function were assessed by means of (99m)Tc-DTPA and (99m)Tc-EC clearance, respectively. Urinary markers of glomerular dysfunction (albumin) and tubular damage (α1-microglobulin (α1M), ß2-microglobulin (ß2M), retinol-binding protein (RBP), N-acetyl-ß-glucosaminidase (NAG) activity) were determined using latex beads tests or colorimetry. The lead concentration in blood was measured with atomic absorption spectrometry. RESULTS: The blood lead concentrations were 145.8 (121.3-175.3) and 39.3 (35.1-44.1) µg/l (geometric mean, 95(th) CI, p<0.001) in the exposed and control groups, respectively. Subjects exposed to lead presented with increased (99m)Tc-DTPA clearance (158.3 (148.4-168.8) vs. 135.9 (127.9-144.4) ml/min; p<0.01) and urinary albumin excretion (7.61 (6.28-9.22) vs. 4.78 (4.05-5.65) mg/g creatinine; p<0.001). (99m)Tc-EC clearance and excretion of α1M, ß2M, RBP and NAG were not significantly different between the groups. Significant correlations between (99m)Tc-DTPA clearance and blood lead concentrations (r=0.45; p<0.01) and between urinary albumin excretion and blood lead concentrations (r=0.71; p<0.001) were noted. CONCLUSIONS: Use of renal scintigraphy in present study revealed measurable alterations of renal function under the conditions of low-level lead exposure and suggest that increased glomerular filtration may be an early indicator of kidney damage in subjects occupationally exposed to lead.

Oxidative DNA damage and oxidative stress in subjects occupationally exposed to nitrous oxide (N(2)O).

OBJECTIVES: Occupational exposure to nitrous oxide (N(2)O) and/or halogenated hydrocarbons has been suggested to induce damage of genetic material, but the underlying mechanisms remain obscure. This study investigated the role of oxidative processes in the genotoxicity associated with exposure to waste anaesthetic gases. METHODS: The study was performed in 36 female nurses and in 36 unexposed female health care workers matched for age and employment duration. Genotoxic effects were examined by Comet test modification employing formamidopyrimidine glycosylase (FPG) that allows assessment of oxidative DNA damage. Reactive oxygen species (ROS) in leukocytes were investigated by fluorescence spectroscopy with 2',7'-dichlorofluorescin diacetate. Oxidative stress markers including 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)), thiobarbituric acid-reacive substances (TBARS), α-tocopherol, and glutathione peroxidise (GPX) activity were measured immuno- or colorimetrically. N(2)O, sevoflurane and isoflurane were monitored by gas chromatography and mass spectrometry. RESULTS: The study documents for the first time the positive correlation between the oxidative DNA damage and the N(2)O levels in the ambient air. By contrast, no association was observed between genotoxic effects and sevoflurane or isoflurane. In addition, ROS generation and plasma and urine concentrations of TBARS and 8-iso-PGF(2α), respectively, were elevated, while GPX activity was reduced in nurses exposed to waste anaesthetic gases. Path analysis pointed to a causal relationship between N(2)O exposure, oxidative stress and DNA damage. CONCLUSION: Occupational exposure to N(2)O is associated with increased oxidative DNA damage and the level of exposure plays a critical role in this regard. Increased oxidative stress may represent a mechanistic link between chronic N(2)O exposure and genotoxicity.

DNA damage induced by nitrous oxide: study in medical personnel of operating rooms.

Occupational exposure to anaesthetics such as nitrous oxide (N(2)O) and halogenated hydrocarbons has been suggested to increase risk of genetic damage. However, the dose-dependency of genotoxic effects has not been unequivocally established and their relation to occupational exposure limit (OEL) remain obscure. In this study, the genotoxicity associated with occupational exposure to anaesthetics has been investigated in a group of 55 female nurses and 29 male anaesthesiologists active for at least 5 years in a working environment containing variable concentrations of N(2)O and halogenated hydrocarbons. 83 unexposed health care workers (52 female nurses and 31 male doctors) matched for age, gender, smoking habit and employment duration were included in the control group. Genotoxicity has been assessed using comet test. Concentrations of nitrous oxide, sevoflurane and isoflurane monitored by gas chromatography and mass spectrometry made possible to relate the extent of DNA damage to the level of exposure. Our results for the first time document a positive correlation between the DNA damage and the N(2)O levels in the ambient air. By contrast, no correlation has been observed between genotoxic effects and concentrations of sevoflurane and isoflurane. The extent of genetic injury was especially aggravated among nurses and anaesthesiologists exposed to N(2)O in concentrations exceeding OEL (180 mg/m(3)). We conclude that occupational exposure to N(2)O is associated with increased DNA damage and that the level of exposure plays a critical role in this regard.

Occupational exposure to nitrous oxide - the role of scavenging and ventilation systems in reducing the exposure level in operating rooms.

OBJECTIVES: The aim of this study was to assess the level of occupational exposure to nitrous oxide (N(2)O) in operating rooms (ORs), as related to different ventilation and scavenging systems used to remove waste anaesthetic gases from the work environment. METHODS: The monitoring of N(2)O in the air covered 35 ORs in 10 hospitals equipped with different systems for ventilation and anaesthetic scavenging. The examined systems included: natural ventilation with supplementary fresh air provided by a pressure ventilation system (up to 6 air changes/h); pressure and exhaust ventilation systems equipped with ventilation units supplying fresh air to and discharging contaminated air outside the working area (more than 10 air changes/h); complete air-conditioning system with laminar air flow (more than 15 air changes/h). The measurements were carried out during surgical procedures (general anaesthesia induced intravenously and maintained with inhaled N(2)O and sevofluran delivered through cuffed endotracheal tubes) with connected or disconnected air scavenging. Air was collected from the breathing zone of operating personnel continuously through the whole time of anaesthesia to Tedlar((R)) bags, and N(2)O concentrations in air samples were analyzed by adsorption gas chromatography/mass spectrometry. RESULTS: N(2)O levels in excess of the occupational exposure limit (OEL) value of 180mg/m(3) were registered in all ORs equipped with ventilation systems alone. The OEL value was exceeded several times in rooms with natural ventilation plus supplementary pressure ventilations and twice or less in those with pressure/exhaust ventilation systems or air conditioning. N(2)O levels below or within the OEL value were observed in rooms where the system of air conditioning or pressure/exhaust ventilation was combined with scavenging systems. Systems combining natural/pressure ventilation with scavenging were inadequate to maintain N(2)O concentration below the OEL value. CONCLUSION: Air conditioning and an efficient pressure/exhaust ventilation (above 12 air exchanges/h) together with efficient active scavenging systems are sufficient to sustain N(2)O exposure in ORs at levels below or within the OEL value of 180mg/m(3).

Evidence for oxidative stress at elevated plasma thiol levels in chronic exposure to carbon disulfide (CS2) and coronary heart disease.

OBJECTIVES: Oxidative stress in plasma may be promoted by plasma thiols such as homocysteine. However, other thiols such as glutathione may also exert antioxidant effects in vitro and in vivo. To further investigate whether plasma thiols act as prooxidants or antioxidants, we compared plasma oxidative status in patients with coronary heart disease (CHD) and in subjects occupationally exposed to carbon disulfide (CS(2)). METHODS: Fifty-five subjects chronically exposed to CS(2), 53 CHD patients, and 52 healthy controls were examined. To assess plasma oxidative status, concentrations of thiobarbituric reactive substances (TBARS) and total antioxidative capacity (TAC), as well as ferritin and ceruloplasmin were determined. Antioxidative reserve was assessed by the determination of vitamine E, uric acid, superoxide dismutase, catalase, and glutathion peroxidase. In addition, protein and non-protein plasma thiol levels were measured. RESULTS: Patients in both groups had increased levels of plasma thiols as compared to controls: CS(2)-exposed subjects presented with increased levels of thiols associated with plasma proteins, whereas CHD patients presented with elevated total homocysteine and cysteine levels. TBARS were significantly increased and TAC was significantly decreased both in CS(2)-exposed subjects and in CHD patients. In addition decreased activity of glutathione peroxidase, an antioxidative enzyme inhibited by thiol-containing compounds, was noted in both groups. CONCLUSION: These results demonstrate that regardless of their metabolic origin increased thiols are associated with increased oxidative stress in plasma.

Combined exposure to m-xylene and ethanol: oxidative stress in the rat liver.

OBJECTIVES: Ethanol may be a significant combined factor in human solvent toxicity. Lipid peroxidation has been suggested to be an important contributing mechanism involved in experimental alcohol-induced liver injury. The aim of the study was to investigate whether a short-term ethanol ingestion in rats chronically exposed to m-xylene vapor may influence the lipid peroxidation rate in the intracellular hepatic membranes, the level of glutathione and the activity of glutathione-related enzymes in the liver. MATERIALS AND METHODS: Experiments were performed on male Wistar rats (outbred IMP:WIST) exposed to m-xylene (5 months, 5 h/day), at a low concentration (400 mg/m3), and/or acute ethanol administration (6 oral doses of 0.25 g/100 g b.w. at 12 h intervals, for the last 3 days of xylene exposure). To estimate the oxidative stress in the liver, lipid peroxidation rate in microsomal and lysosomal membranes, glutathione sulfhydryls levels, and glutathione-S-transferase activity were determined. RESULTS: The studies indicated that combined exposure to ethanol and m-xylene, as distinct from the chronic exposure to m-xylene alone, led to the increased lipid peroxidation rate in microsomal and lysosomal membranes with a simultaneous decrease in the levels of glutathione sulfhydryls and glutathione-S-transferase activity. CONCLUSIONS: We conclude that the enhanced lipid peroxidation rate in the intracellular hepatic membranes may be an important agent in combined ethanol/xylene-induced hepatotoxicity.

Increased oxidative stress in subjects exposed to carbon disulfide (CS2)--an occupational coronary risk factor.

There is considerable epidemiological evidence that workers exposed to carbon disulfide (CS2) develop premature atherosclerosis leading to increased rates of coronary heart disease (CHD), but mechanisms underlying this association remain obscure. The present study documents that occupational exposure to CS2 modifies the oxidative status of plasma, which is a major determinant of the susceptibility to atherosclerosis. Concentrations of thiobarbituric reactive substances (TBARS), which reflect lipid peroxidation processes in plasma, were determined in 29 men who were exposed to CS2 for more than 20 years, in 24 patients with peripheral atherosclerosis, and in 30 unexposed, healthy control subjects. TBARS concentrations were significantly increased both in CS2-exposed subjects and in patients with peripheral atherosclerosis. Subjects in both groups presented also with decreased levels of plasma alpha-tocopherol, a major plasma antioxidant. In addition, decreased activities of two enzymatic antioxidants, glutathion peroxidase and catalase, were noted both in CS2-exposed subjects and patients with peripheral atherosclerosis. Finally, LDL isolated from both groups showed increased susceptibility to transition metal-induced oxidation in vitro. It is concluded, that occupational exposure to CS2 produces oxidative stress in plasma. This may favor the development of atherosclerosis and increase the incidence of CHD in workers exposed to CS2.