Andrzej Sapota

Disturbed homeostasis of zinc and other essential elements in the prostate gland dependent on the character of pathological lesions

Pathophysiological changes in the prostate take the form of benign prostate hyperplasia (BPH) and prostate adenocarcinoma (PCa). In prostate, zinc is particularly important to its normal functioning, especially in terms of the consequences of hormone disturbance. The aim of this study was to assess the levels of Zn, Cu, Ca, Mg, and Se in the prostate dependent on the character of patological changes. Zinc, copper, magnesium and calcium were determined by AAS and selenium with spectrofluorometric method. Zn levels in BPH patients were over twofold higher than in controls. On the other hand, in the patients with PCa, the levels of Zn were found almost three times lower than in BPH patients and by almost 50% lower than in controls. In this study, significant changes in the levels of other essential elements were observed. The results apparently confirm the disturbed homeostasis of zinc and other essential elements in the etiology of BPH and PCa.

New inhibitors of protein kinase CK2, analogues of benzimidazole and benzotriazole

Derivatives of 4,5,6,7-tetrabromobenzotriazole (TBBt) and 4,5,6,7-tetrabromobenzimidazole (TBBi) with IC50 in the low micromolar range and with high selectivity belong to the most promising inhibitors of protein kinase CK2 (casein kinase 2). Treatment of various cell lines with TBBt, TBBi or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) affected cell viability with simultaneous induction of apoptosis. The inhibitory activity of newly synthesized hydroxyalkyl derivatives of TBBi and TBBt depends on the length of the alkyl chain. The hydroxypropyl substituted derivatives show higher or similar inhibitory activity than the parent compounds when tested with human protein kinase CK2. To test the distribution of this class of compounds in mammals, [14C] TBBi was synthesized.

Subacute toxicity of polychlorinated naphthalenes and their effect on cytochrome P-450.

The aim of the study was to investigate the subacute toxicity of a polychlorinated naphthalene (PCN) mixture and its effect on cytochrome P-450 levels in rats. The animals were administered PCNs intragastrically in repeated daily doses of 1, 10, and 100 mg/kg. The animals were dissected after 7, 14, or 21 doses. Doses of 10 and 100 mg/kg induced a significant decrease in the body weight at all time points of the experiment compared with the control group. The exposure to PCNs increased both the level of total cytochrome P-450 and the activity of CYP 1A at the same time points. In the groups of rats given PCNs in doses of 10 and 100 mg/kg, an evident dose- and time-dependent increase in malondialdehyde (MDA) level was observed throughout the experiment. The correlation between the increased MDA and decreased glutathione (GSH) levels in the liver was also observed.

Chemical composition of surgical smoke formed in the abdominal cavity during laparoscopic cholecystectomy – Assessment of the risk to the patient

ObjectivesThe aim of this study was to assess the exposure of patients to organic substances produced and identified in surgical smoke formed in the abdominal cavity during laparoscopic cholecystectomy.Material and MethodsIdentification of these substances in surgical smoke was performed by the use of gas chromatography-mass spectrometry (GC-MS) with selective ion monitoring (SIM). The selected biomarkers of exposure to surgical smoke included benzene, toluene, ethylbenzene and xylene. Their concentrations in the urine samples collected from each patient before and after the surgery were determined by SPME-GC/MS.ResultsQualitative analysis of the smoke produced during laparoscopic procedures revealed the presence of a wide variety of potentially toxic chemicals such as benzene, toluene, xylene, dioxins and other substances. The average concentrations of benzene and toluene in the urine of the patients who underwent laparoscopic cholecystectomy, in contrast to the other determined compounds, were significantly higher after the surgery than before it, which indicates that they were absorbed.ConclusionsThe source of the compounds produced in the abdominal cavity during the surgery is tissue pyrolysis in the presence of carbon dioxide atmosphere. All patients undergoing laparoscopic procedures are at risk of absorbing and excreting smoke by-products. Exposure of the patient to emerging chemical compounds is usually a one-time and short-term incident, yet concentrations of benzene and toluene found in the urine were significantly higher after the surgery than before it.

Disposition and metabolism of 1,6-dimethylnaphthalene in rats

The distribution, excretion and metabolism of 1,6-dimethylnaphthalene following i.p. administration of a single dose of 20 mg/kg to rats, was investigated using radiotracer [3H] and a gas chromatography-mass spectrometry technique (GC-MS). After 72 h, about 94% of the given dose was excreted in urine and feces. In organs and tissues, the highest concentration during the first hours after administration was detected in fat, liver, spleen and kidneys. Then gradual decline of tritium was noticed in all examined tissues. In urine, the following substances were identified and quantified by GC peak areas: unchanged 1,6-dimethylnaphthalene, 1-methyl-hydroxynaphthalenes, 1-hydroxymethyl-6-methylnaphthalene, 1,6-dimethyl-thionaphthalene, 6-methyl-1-naphthoic aldehyde, 6-methyl-1-naphthoic acid, 1,6-dimethyl-thionaphthalene and 1,6-dimethyl-methylthionaphthalene.

Developmental toxicity of hexachloronaphthalene in Wistar rats. A role of CYP1A1 expression.

Hexachloronaphthalene (HxCN) is one of the most toxic congeners of polychlorinated naphthalenes (PCNs). This study assesses the prenatal toxicity of HxCN after daily administration at doses of 0.1-1.0mg/kg b.w. to pregnant Wistar rats during organogenesis. We evaluated also the expression of CYP1A1 mRNA and protein in the livers of dams and fetuses, as well as the placenta. The results indicate that 0.3mg/kg b.w. was the lowest HxCN toxic dose for dams (LOAEL) while a dose of 0.1mg/kg b.w. was sufficient to impair the intrauterine development of embryos/fetuses without maternal toxicity. Regardless of the applied dose, HxCN generated embryotoxic effects. Dose-dependent fetotoxic effects were associated with HxCN exposure. HxCN was found to be a strong inducer of maternal and fetal CYP1A1. Expression of CYP1A1 mRNA in the placenta appears to be the most sensitive marker of HxCN exposure.

The disposition and metabolism of 1,3,5-[U-14C]trioxane in male Wistar albino rats

Abstract The present study was designed to investigate 1,3,5-[U-14C]trioxane (TOX) distribution, excretion and metabolism. The experiments were performed on male Wistar albino rats after a single administration of TOX at doses of 40 mg/kg and 400 mg/kg. The exhaled air proved to be the main route of 14C elimination, mainly as 14CO2. During the first 12 h following the administration of 40 mg/kg of TOX the exhalation of 14CO2 was monophasic, with a half-life of 3.5 h. After the administration of 400 mg/kg, TOX was eliminated mainly as 14CO2 with the exhaled air (77%) and unchanged TOX (8%). About 3% of 14C was excreted in the urine as unchanged 1,3,5-trioxane. With regards to TOX elimination from blood plasma for the lower dose, a biphasic process was observed, with half-lives of 4.5 and 72 h. The amount of 14C bound by the erythrocytes was minute compared with the amount in blood plasma. When the higher dose of TOX was administered the efficiency of 14C binding to the erythrocytes was found to be 10 times higher than the respective value for blood plasma. Among the examined tissues the highest concentration of TOX-derived radioactivity was detected in the liver while the lowest was in fat tissue and brain. A subsequent decay of radioactivity occurred in the tissues. The results of the present study indicate that TOX belongs to the group of compounds, which are rapidly eliminated from the organism; hence TOX should not be expected to accumulate within the tissues. The data obtained confirm the assumed pattern of metabolic transformation, according to which 1,3,5-trioxane undergoes enzymatic transformation to formaldehyde, with carbon dioxide and water being the final products.

Health risk to medical personnel of surgical smoke produced during laparoscopic surgery.

OBJECTIVES During laparoscopic cholecystectomy, the removal of the gall bladder, pyrolysis occurs in the peritoneal cavity. Chemical substances which are formed during this process escape into the operating room through trocars in the form of surgical smoke. The aim of this study was to identify and quantitatively measure a number of selected chemical substances found in surgical smoke and to assess the risk they carry to medical personnel. MATERIAL AND METHODS The study was performed at the Maria Skłodowska-Curie Memorial Provincial Specialist Hospital in Zgierz between 2011 and 2013. Air samples were collected in the operating room during laparoscopic cholecystectomy. RESULTS A complete qualitative and quantitative analysis of the air samples showed a number of chemical substances present, such as aldehydes, benzene, toluene, ethylbenzene, xylene, ozone, dioxins and others. CONCLUSIONS The concentrations of these substances were much lower than the hygienic standards allowed by the European Union Maximum Acceptable Concentration (MAC). The calculated risk of developing cancer as a result of exposure to surgical smoke during laparoscopic cholecystectomy is negligible. Yet it should be kept in mind that repeated exposure to a cocktail of these substances increases the possibility of developing adverse effects. Many of these compounds are toxic, and may possibly be carcinogenic, mutagenic or genotoxic. Therefore, it is necessary to remove surgical smoke from the operating room in order to protect medical personnel.

Selected oxidative stress parameters after single and repeated administration of octabromodiphenyl ether to rats.

ObjectivesOctabromodiphenyl ether (OctaBDE) was used as a flame retardant applied mostly in the manufacture of plastics utilized in the electrical and electronic industries. Owing to its long half-life and being regarded as an environmental pollutant, OctaBDE, like other polybrominated diphenyl ethers, has been classified as a persistent organic pollutant (POP). This study was carried out to assess the effects of oxidative stress (redox homeostasis) induced in rats by OctaBDE.Material and MethodsFemale Wistar rats exposed intragastrically to OctaBDE at single (25, 200 or 2000 mg/kg b.w.), or repeated (0.4, 2, 8, 40 or 200 mg/kg/day) doses during 7–28 days were used in the experiment. Selected oxidative stress parameters were determined in the liver and blood serum.ResultsAdministration (single or repeated) of OctaBDE to rats resulted in the impaired redox homeostasis, as evidenced by the increased levels of reduced (GSH) and oxidized (GSSG) glutathione in the liver, the reduced total antioxidant status (TAS) in serum and the increased concentration of malondialdehyde (MDA) in the liver. After multiple doses of OctaBDE, elevated activity of glutathione transferase (GST) in the liver was also noted.ConclusionsAfter repeated administration of OctaBDE at the lowest dose (0.4 mg/kg/day), changes were observed in the parameters (MDA, TAS, GSSG) indicative of oxidative stress.