- Email: [email protected]
Rat liver microsomal monooxygenase system after ethanol and ethylene glycol administration
S64
Abstracts / Toxicology Letters 164S (2006) S1–S324
these glutathione and protein SH-groups contents as well as liver glutathione reductase and catalase activity were decreased. The rate of induced malonodialdehyde (MDA) formation, hydroperoxides and super oxide anion contents were increased in comparison to the control. Alanine aminotransferase (AlAT) activity elevated in blood serum of 1.7-fold the upper limit of normal. After chronic ethanol consumption feeding for 6 months, aniline-N-hydroxylase, glutathione reductase, AlAT activities and MDA formation was increased significantly, whereas content of glutathione were decreased compared with control. After parallel administration of acetaminophen (dose—500 mg/kg b.w.) the activities of aniline-N-hydroxylase followed up 65% and the serum ALAT activities increased of 5.6-fold. In acetaminophen-treated animals, ethanol-fed rats showed a significant decreased hepatic glutathione levels. Our results suggest that ethanol may be an additional risk factor for developing acetaminophen hepatotoxicity. The observation that acetaminophen and alcohol intensify the induction of CYP2E1 in a synergistic manner may help to understand and to prevent an additional risk factor for developing acetaminophen hepatotoxicity. doi:10.1016/j.toxlet.2006.06.132 P1-03 Rat liver microsomal monooxygenase system after ethanol and ethylene glycol administration Andrzej Plewka 1 , Joanna Kowalowka-Zawieja 2 , 2 Jedrzej Przystanowicz , Danuta Plewka 1 , Grazyna 1 Nowaczyk-Dura , Barbara Zielinska-Psuja 2 , Jerzy 2 Orlowski 1 Medical 2 Poznan
University of Silesia, Katowice, Poland; University of Medical Sciences, Poznan,
Poland Ethylene glycol (EG) is a popular component of antifreeze coolants, windscreen cleaners and de-icers used in automotive industry. Ingestion of EG solutions results in conversion of relatively non-toxic glycol into highly toxic metabolites. Ethanol (EtOH) administered i.v. restricts first step of EG biotransformation by competitive inhibition of alcohol dehydrogenase. This is a key enzyme in metabolic route of both xenobiotics, a smaller amount of them is transformed by microsomal monooxygenase system. We evaluated the effect of separate and simultaneous per os administration of ethylene glycol (3830 mg/kg b.w.) and ethanol (1000 mg/kg b.w.) on CYP450 and
cytochrome b5 concentrations and activities of their reductases in rat liver. Tests were performed 8, 12, 18, 24, 36 and 48 h after exposure. In rats exposed to EtOH amount of microsomal protein was elevated to 115% of control after 8 h and 150% at the end of experiment. EG administration, single or simultaneous with EtOH, resulted in substantial decrease of protein amount in period 24–48 h to 85% and 80%, respectively. A continuing decrease to 66% of control in CYP450 concentrations in EG group was measured in 24–48 h period. EtOH elevated CYP450 concentration to 110% and 145% of control after 8 and 48 h, respectively. Exposure to both xenobiotics resulted in decrease of concentration to 70–80% in whole time of experiment. Activity of CYP450 reductase increased to 125% and 150% after 48 h in EG and EG with EtOH group, respectively. After EtOH administration the activity decreased to 70% after 18 h, to reach 90% of control after 48 h. Cytochrome b5 concentrations after EG administration were 90–65% of control in 18–48 h without effect on cytochrome b5 reductase. Similar results were obtained after EtOH administration (80–70% of concentration in control group). Simultaneous exposure to both alcohols resulted in decrease of cytochrome b5 concentration and its reductase activity (80% after 8 h and 60% after 36 h). doi:10.1016/j.toxlet.2006.06.133 P1-04 The effect of ethanol and ethylene glycol administration on CYP450 and cytochrome b5 concentrations and their reductases activities in rat kidney Andrzej Plewka 1 , Joanna Kowalowka-Zawieja 2 , 2 Jedrzej Przystanowicz , Danuta Plewka 1 , Grazyna 1 Nowaczyk-Dura , Barbara Zielinska-Psuja 2 , Jerzy 2 Orlowski 1 Medical 2 Poznan
University of Silesia, Katowice, Poland; University of Medical Sciences, Poznan,
Poland Ethylene glycol (EG) is extensively metabolised into acid and aldehyde compounds what results in direct renal failure. Ethanol is commonly used in acute EG poisonings to prevent toxic metabolite formation. The aim of the study was to assess the influence of ethylene glycol and ethanol on microsomal monooxygenase system in kidney. Male Wistar rats were exposed separately or simultaneously per os to EG (3830 mg/kg b.w.) and ethanol (1000 mg/kg b.w.). Cytochrome P450 and
Abstracts / Toxicology Letters 164S (2006) S1–S324
these glutathione and protein SH-groups contents as well as liver glutathione reductase and catalase activity were decreased. The rate of induced malonodialdehyde (MDA) formation, hydroperoxides and super oxide anion contents were increased in comparison to the control. Alanine aminotransferase (AlAT) activity elevated in blood serum of 1.7-fold the upper limit of normal. After chronic ethanol consumption feeding for 6 months, aniline-N-hydroxylase, glutathione reductase, AlAT activities and MDA formation was increased significantly, whereas content of glutathione were decreased compared with control. After parallel administration of acetaminophen (dose—500 mg/kg b.w.) the activities of aniline-N-hydroxylase followed up 65% and the serum ALAT activities increased of 5.6-fold. In acetaminophen-treated animals, ethanol-fed rats showed a significant decreased hepatic glutathione levels. Our results suggest that ethanol may be an additional risk factor for developing acetaminophen hepatotoxicity. The observation that acetaminophen and alcohol intensify the induction of CYP2E1 in a synergistic manner may help to understand and to prevent an additional risk factor for developing acetaminophen hepatotoxicity. doi:10.1016/j.toxlet.2006.06.132 P1-03 Rat liver microsomal monooxygenase system after ethanol and ethylene glycol administration Andrzej Plewka 1 , Joanna Kowalowka-Zawieja 2 , 2 Jedrzej Przystanowicz , Danuta Plewka 1 , Grazyna 1 Nowaczyk-Dura , Barbara Zielinska-Psuja 2 , Jerzy 2 Orlowski 1 Medical 2 Poznan
University of Silesia, Katowice, Poland; University of Medical Sciences, Poznan,
Poland Ethylene glycol (EG) is a popular component of antifreeze coolants, windscreen cleaners and de-icers used in automotive industry. Ingestion of EG solutions results in conversion of relatively non-toxic glycol into highly toxic metabolites. Ethanol (EtOH) administered i.v. restricts first step of EG biotransformation by competitive inhibition of alcohol dehydrogenase. This is a key enzyme in metabolic route of both xenobiotics, a smaller amount of them is transformed by microsomal monooxygenase system. We evaluated the effect of separate and simultaneous per os administration of ethylene glycol (3830 mg/kg b.w.) and ethanol (1000 mg/kg b.w.) on CYP450 and
cytochrome b5 concentrations and activities of their reductases in rat liver. Tests were performed 8, 12, 18, 24, 36 and 48 h after exposure. In rats exposed to EtOH amount of microsomal protein was elevated to 115% of control after 8 h and 150% at the end of experiment. EG administration, single or simultaneous with EtOH, resulted in substantial decrease of protein amount in period 24–48 h to 85% and 80%, respectively. A continuing decrease to 66% of control in CYP450 concentrations in EG group was measured in 24–48 h period. EtOH elevated CYP450 concentration to 110% and 145% of control after 8 and 48 h, respectively. Exposure to both xenobiotics resulted in decrease of concentration to 70–80% in whole time of experiment. Activity of CYP450 reductase increased to 125% and 150% after 48 h in EG and EG with EtOH group, respectively. After EtOH administration the activity decreased to 70% after 18 h, to reach 90% of control after 48 h. Cytochrome b5 concentrations after EG administration were 90–65% of control in 18–48 h without effect on cytochrome b5 reductase. Similar results were obtained after EtOH administration (80–70% of concentration in control group). Simultaneous exposure to both alcohols resulted in decrease of cytochrome b5 concentration and its reductase activity (80% after 8 h and 60% after 36 h). doi:10.1016/j.toxlet.2006.06.133 P1-04 The effect of ethanol and ethylene glycol administration on CYP450 and cytochrome b5 concentrations and their reductases activities in rat kidney Andrzej Plewka 1 , Joanna Kowalowka-Zawieja 2 , 2 Jedrzej Przystanowicz , Danuta Plewka 1 , Grazyna 1 Nowaczyk-Dura , Barbara Zielinska-Psuja 2 , Jerzy 2 Orlowski 1 Medical 2 Poznan
University of Silesia, Katowice, Poland; University of Medical Sciences, Poznan,
Poland Ethylene glycol (EG) is extensively metabolised into acid and aldehyde compounds what results in direct renal failure. Ethanol is commonly used in acute EG poisonings to prevent toxic metabolite formation. The aim of the study was to assess the influence of ethylene glycol and ethanol on microsomal monooxygenase system in kidney. Male Wistar rats were exposed separately or simultaneously per os to EG (3830 mg/kg b.w.) and ethanol (1000 mg/kg b.w.). Cytochrome P450 and