Influence of ezetimibe on selected parameters of oxidative stress in rat liver subjected to ischemia/reperfusion.

INTRODUCTION: Ischemia/reperfusion (I/R) is considered to be one of the main causes of liver damage after transplantation. The authors evaluated the effect of ezetimibe on selected oxidative stress parameters in ischemic/reperfused (I/R) rat liver. MATERIAL AND METHODS: Rats were administered ezetimibe (5 mg/kg) (groups E and E-I/R) or saline solution (groups C and C-I/R) intragastrically for 21 days. Livers of animals in groups C-I/R and E-I/R were subjected to 60 min of partial ischemia (left lateral and median lobes) followed by 4 h of reperfusion. Alanine and asparagine aminotransferase (ALT, AST) activity was determined in blood before I/R and during reperfusion (at 15 and 240 min). After the reperfusion period, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GPx) were determined in liver homogenates using colorimetric methods. RESULTS: Ezetimibe caused a significant increase in GSH level in groups subjected to I/R (E-I/R (99.91 ±9.01) vs. C-I/R (90.51 ±8.87), p < 0.05). Additionally, under I/R the decrease of GPx activity in the drug-treated group was lower compared to the non-treated group (E-I/R (3.88 ±1.11) vs. E (5.31 ±1.83), p = 0.076). Neither ezetimibe nor I/R affected SOD or MDA levels. I/R produced a significant increase in aminotransferase levels (ALT240-0: C-I/R (42.23 ±43.56) vs. C (9.75 ±11.09), and E-I/R (39.85 ±26.53) vs. E (4.38 ±1.36), p < 0.05 in both cases; AST 240-0: E-I/R (53.87 ±17.23) vs. E (24.10 ±9.66), p < 0.05) but no effect of ezetimibe on those enzymes was found. CONCLUSIONS: Ezetimibe demonstrates antioxidant properties in rat livers subjected to I/R. However, neither a hepatoprotective nor a hepatotoxic effect of ezetimibe was demonstrated, regardless of I/R.

Effect of simvastatin treatment on rat livers subjected to ischemia/reperfusion.

We evaluated the effect of simvastatin (SV) on the oxido-redox state in rat livers submitted to ischemia-reperfusion (I/R). Rats received SV (groups: S, S-IR) or saline solution (groups: C, C-IR) intragastrically (25 mg/kg) for 21 days. Before homogenization, rat livers (C-IR, S-IR) underwent ischemia (40 min) and reperfusion (60 min). Activities of such antioxidative enzymes as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) as well as lipid peroxides (LPO) level as indicator of oxidative stress were then estimated in the homogenates. All these parameters were measured spectrophotometrically. Additionally, alanine and asparagine aminotransferase (ALT, AST) levels were estimated in the blood before and after I/R. In groups C and S all examined parameters were similar regardless of SV-treatment. I/R produced significant increases in GPx and CAT activities only in the C-IR group. Conversely, GPx activity was significantly decreased and ALT and AST increased significantly in the S-IR group. SV did not evoke any noticeable protective changes in rat livers after 3 weeks of treatment. After I/R, some of the observed properties could suggest that SV may have even made liver function and the oxidative state worse.

Effect of simvastatin on nitric oxide synthases (eNOS, iNOS) and arginine and its derivatives (ADMA, SDMA) in ischemia/reperfusion injury in rat liver.

Hydroxymethylglutaryl-CoA reductase inhibitors play a role in nitric oxide synthesis. In this study, the impact of simvastatin (SV) on the levels of nitric oxide synthases, and arginine (Arg) and its derivatives was evaluated in rat liver under ischemia-reperfusion (I/R) conditions. Rats received SV (25 mg/kg) (groups S and S-IR) or saline solution (groups C and C-IR) intragastrically for 21 days. The livers of groups C and S were homogenized after treatment while those of groups C-IR and S-IR underwent ischemia and reperfusion before homogenization. Endothelial (eNOS) and inducible (iNOS) nitric oxide synthase concentrations were determined in the homogenates. Alanine and asparagine aminotransferase (ALT, AST, respectively), arginine (Arg), and asymmetric (ADMA) and symmetric (SDMA) methylarginine levels were determined in the blood before I/R and during reperfusion. I/R injury produced significant increases in aminotransferase, ADMA, eNOS, and iNOS, but decreases in Arg and Arg/ADMA levels. Arg concentration increased significantly after warm ischemia in the S-IR group, but decreased significantly during the first 30 minutes of reperfusion in both the S-IR and C-IR groups. eNOS concentration was significantly higher in group S than in group C. Both I/R and SV exerted no influence on SDMA concentration. SV exerted a protective action by increasing eNOS levels under normal conditions and Arg levels after ischemia and by preventing a significant increase in iNOS concentration after I/R. SV had no effect on ADMA concentration under normal and pathological conditions.

Influence of water-soluble flavonoids, quercetin-5'-sulfonic acid sodium salt and morin-5'-sulfonic acid sodium salt, on antioxidant parameters in the subacute cadmium intoxication mouse model.

Water-soluble quercetin-5'-sulfonic acid sodium salt (NaQSA) and morin-5'-sulfonic acid sodium salt (NaMSA) could exert an antagonistic effect on cadmium intoxication. The aim of the study was to examine the influence of these substances on superoxide dismutase (SOD) and glutathione (GSH) levels in the mouse liver in the subacute cadmium intoxication model. NaQSA and NaMSA significantly counteracted cadmium-induced decreases in SOD and GSH levels. No significant differences in SOD and GSH levels between groups exposed to cadmium receiving NaQSA or/and NaMSA were observed.

[The influence of occupational lead exposure on transmural repolarization dispersion]. / Wplyw zawodowego narazenia na olów na przezscienna dyspersje repolaryzacji.

UNLABELLED: The parts of QT interval: time from Q wave to the peak of T wave (QTp) representing the de- and repolarization of subepicardial layer and the time from the peak of T wave to its end (QTp-e) building the transmural dispersion of repolarization enable more exact assessment of repolarization period of the heart muscle. Occupational exposure to lead influences the electrophysiologic properties of the heart. The aim of our study was to assess the QTp and QTp-e interval in workers occupationally exposed to lead. MATERIAL AND METHOD: The study was carried out in 22 copper smelters aged 41.8 +/- 8.7 years, occupationally exposed to lead. The control group consisted of 14 healthy men. In all studied subjects blood lead concentration (Pb) and the concentration of free protoporphyrins in erytrocytes were assessed. 24-hour ECG holter monitoring was done to study rhythm disturbances and the duration in lead CM5 of QT interval, QTp interval, RR interval preceding the assessed QT interval (pRR) during sleep, rest during the awake state and moderate daily activity. The QTp-e interval is the difference between the duration of QT and QTp interval. The duration of QTp and QTp-e in occupationally exposed workers and healthy persons did not differ significantly. These parameters were significantly lower in both groups during moderately physical activity comparing to the values during sleep. The QTp-e/ QTp ratio in occupationally exposed workers during night hours was significantly lower than during daily activity what was not the case in control persons. Occupational exposure to lead do not change significantly the transmural dispersion of repolarization. Occupational exposure to lead diminishes the QTp-e/QTp ratio during the night.

Heart rate variability in workers chronically exposed to lead.

BACKGROUND: Lead is a strong neurotoxin. The effects of lead on the activity of the autonomic nervous system, assessed by the use of heart rate variability (HRV) analysis, have not yet been established. AIM: To assess the effects of occupational chronic lead exposure on the autonomic nervous system activity. METHODS: The study group consisted of 22 copper foundry workers (mean age 41.8+/-8.7 years) who had elevated parameters of lead overload and were admitted to the hospital for chelate therapy. The control group consisted of 13 age-matched healthy males. Lead concentration was measured with the use of atomic absorption spectrophotometry, and concentration of free protoporphyrins in erythrocytes (FEP) using a fluorometric method. Each patient underwent 24-hour ambulatory ECG monitoring, and standard short-term as well as long-term HRV parameters were obtained. RESULTS: There were no significant differences between patients and controls in HRV parameters. In the control group, HRV parameters correlated with age. In patients, a significant negative correlation between lead concentration and some short-term HRV parameters calculated during the night was found: SDNN (r=-0.48, p<0.05), TP (r=-0.48, p<0.01) and LF (r=-0.48, p<0.01). In patients, a negative correlation between lead concentration and HFnight/HFday index was found (r=-0.47 p<0.01), whereas in controls this correlation was positive (r=0.66 p<0.05). CONCLUSIONS: Overall HRV indices are similar in subjects exposed to lead and in healthy controls. A decrease in the physiological elevation of HF values during the night, together with an increase in lead blood concentration and lack of relationship between age and HRV parameters in workers chronically exposed to lead may suggest disturbances of the autonomic system. In subjects not exposed to lead a decrease in heart rate with an increase in FEP concentration was observed.

[Acute intermittent porphyria coexisting with chronic postinfectious renal failure]. / Porfiria ostra przerywana wspólistniejaca z przewlekla poinfekcyjn niewydolnoscia nerek.

In this paper a case of 46-year-old woman suffering from the acute intermittent porphyria (AIP) was presented. She developed the chronic renal failure due to the hypertension, reccurent urinary tract infections and neurogenic urinary bladder following the autonomic neuropathy. The patient eventually died in spite of haemodialysis. Skin lesions observed in the last stage of the disease could be an evidence of the possible conversion of AIP in variegate porphyria (VP). However, this suspicion is only the hypothesis due to the lack of the adequate enzymatic lab tests.

[The effect of occupational exposure to heavy metals and arsenic on serum concentrations of carotenoids in copper foundry workers]. / Wplyw ekspozycji zawodowej na olów i arsen na stezenie karotenoidów w surowicy u pracowników huty miedzi.

BACKGROUND: The aim of the project was to analyze the effect of occupational exposure to heavy metals on the efficiency of antioxidative defensive mechanisms, represented by the concentration of carotenoids (KTND) in serum. MATERIALS AND METHODS: The study involved 96 workers exposed to heavy metals in a copper foundry. Two subgroups of workers--those exposed only to lead and those to the combination of lead and arsenic--were analyzed. The control group consisted of 81 subjects not exposed to heavy metals. We measured concentrations of lead and cadmium in whole blood, selenium, manganese, copper, zinc, calcium, magnesium and carotenoids in serum, arsenic in urine and free erythrocyte protoporphyrin (FEP). RESULTS: Serum carotenoids concentration was significantly lower in workers exposed to heavy metals than in the control group (48.76 +/- 15.32 vs. 68.36 +/- 21.46 microg/dl; p < 0.001). There were no significant differences between serum concentrations of carotenoids in the subgroup exposed only to lead and the subgroup exposed to both lead and arsenic ((48.62 +/- 16.64 vs. 48.86 +/- 14.41 microg/dl). We found significant positive correlation between blood cadmium levels and serum carotenoids in the control group (r = -0.3406, p < 0.05). In the multiple regression analysis (optimal model), there was significant negative influence of blood lead on serum KTND levels and positive influence of blood cadmium on serum KTND concentrations in the subgroup of workers exposed only to lead (R(2) A = 0.9102; p < 0.001). In smelters exposed to both lead and arsenic, we observed significant negative influence of FEP and positive influence of arsenic on KTND concentrations in serum in the optimal model of multiple regression (R(2) A = 0.9249; p < 0.001). CONCLUSIONS: Occupational exposure to lead and arsenic in moderate doses affects serum carotenoids concentration in exposed humans.

[Effect of lead on the cardiovascular system]. / Wplyw olowiu na uklad sercowo-naczyniowy.

Lead is a metal widely spread in the natural environment. It is strongly toxic, particularly to the peripheral and central nervous systems. The toxic influence on the cardiovascular system is most pronounced in case of higher exposures, where myocardium and the renal circulation are affected, in consequence of which secondary arterial hypertension can develop. It seems that lead affects the cardiovascular system mainly by changing the peripheral autonomic nervous system and leading to chronic neuropathy. Chronic exposure, even to low doses of lead, can impair conduction in myocardium. In order to assess those changes thoroughly prospective studies involving newly employed workers with occupational exposure to toxic activity of lead will be necessary.

[Effect on manganese on the circulatory system]. / Wplyw manganu na uklad krazenia.

This review describe the effect of manganese on the heart and blood vessels. The interaction between manganese and redox systems and manganese contribution to atherosclerosis development were also investigated. The results of the experimental studies on animals, on isolated blood vessels in vitro and on people professionally exposed to manganese were presented.