Christian Steffen - Academia.edu (original) (raw)
Papers by Christian Steffen
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz, 2006
Zusammenfassung In vitro durchgefhrte experimentelle Untersuchungen konnten nachweisen, dass ein... more Zusammenfassung In vitro durchgefhrte experimentelle Untersuchungen konnten nachweisen, dass einzelne Pathomechanismen der Atherosklerose durch Antioxidantien (z. B. β-Carotin, Vitamin C und Vitamin E) gnstig beeinflusst werden knnen, wobei Vitamin E die deutlichsten Effekte aufwies. Tierexperimentell und in einer Reihe epidemiologischer Studien konnte ein protektiver Effekt von Vitamin E insbesondere unter Verabreichung hoher Dosen nachgewiesen werden. Demgegenber zeigten die meisten der zur primren und sekundren Prvention durchgefhrten placebokontrollierten Studien selbst bei Verabreichung hoher Dosen keinen relevanten protektiven Effekt einer Supplementierung von Antioxidantien (insbesondere von Vitamin E). Darber hinaus wiesen einzelne Untersuchungen auch auf mgliche Nebenwirkungen einer Supplementierung hin. Die vorliegende Arbeit liefert einen berblick ber das Prinzip der Supplementierung von Antioxidantien insbesondere unter Verwendung von Vitamin E und beschreibt die Ergebnisse zahlreicher epidemiologischer und klinischer Studien zur Prvention atherosklerotischer Geferkrankungen. Sie kommt zu dem Ergebnis, dass eine Supplementierung in der Normalbevlkerung derzeit nicht empfohlen werden kann.
Toxicology, 1993
Intoxications with chlorate salts are characterized by methaemoglobin formation, haemolysis and r... more Intoxications with chlorate salts are characterized by methaemoglobin formation, haemolysis and renal insufficiency. The toxic effects on the erythrocyte can be reproduced in vitro. Incubation of human and rabbit erythrocytes with chlorates induces a concentration-dependent oxidation of haemoglobin. This methaemoglobin formation is followed by denaturation of the globin, a cross-linking of erythrocyte membrane proteins and an inactivation of membrane enzymes. The high sensitivity of glucose-6-phosphate dehydrogenase to denaturation by chlorate explains the inefficacy of methylene blue to reduce methaemoglobin formed, as the antidotal effect of methylene blue depends on NADPH formed mainly by the oxidation of glucose-6-phosphate. The observed changes occur only in the presence of methaemoglobin which forms a destabilising complex with chlorate. Methaemoglobin thus autocatalytically increases methaemoglobin formation and destruction of the erythrocyte. As the rabbit is known to have a high methaemoglobin-reduction capacity, human and rabbit erythrocytes were compared. In vitro, the rabbit erythrocyte is less sensitive to oxidative attack than the human red cell. In vivo, an oral dose of sodium chlorate (1 g/kg body wt.) resulted in high serum (16 +/- 4 mM) and urine concentrations (246 +/- 99 mM) in the rabbit. Methaemoglobin was not formed nor could a nephrotoxic effect be observed. These experiments also indicate that the nephrotoxicity of chlorate is mediated by methaemoglobin catalysis.
RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2010
Human Toxicology, 1985
Relle et al., 1984). Reduction in the intracellular content of glutathione was achieved by nutrit... more Relle et al., 1984). Reduction in the intracellular content of glutathione was achieved by nutritional deprivation of L-cysteine or by exposure of cells to D,L-buthionine-S,R-sulphoximine (BSO), a potent inhibitor of y-glutamylcysteine synthetase, and was accompanied by sensitization of melphalan-resistant L1210 cells. We have investigated the effect of BSO on glutathione levels in two types of human leukaemia cells: (1) K562 human chronic myeloid leukaemia cell line; (ii) primary isolates of cyclophosphamide (CP)-resistant chronic lymphocytic leukaemia (CLL) cells. K562 and primary CLL isolates were exposed to BSO at concentrations of 1-500 Rm for 0-24 h periods (three experiments). Glutathione was determined by the Griffith (1980) enzymic recycling method, based on glutathione reductase, as modified by Suzukake et al. (1982). A maximal reduction of approximately 60% in cellular glutathione content was achieved in mid-late log-phase K562 cells and primary CLL isolates by exposure to 50 u,M-BSO for 20 h. This treatment had no effect on cell viability and caused only a slight reduction in colonyforming ability in K562 cells. K562 cells depleted of glutathione were exposed to hepatocyte-activated CP for 1 h and cytotoxicity measured by proliferation and colony-forming assays as described previously (Crook et al., 1985). These cells displayed a very marked increase in sensitivity to CP (Table 1). Moreover, loss of viability was evident as early as 3 h after drug exposure in glutathione-depleted cells but much later in control cells exposed to a CP dose having the same final cytotoxicity. This suggests a separate mechanism of toxicity of CP in glutathione-depleted cells.
Biochemical Pharmacology, 1985
Archives of Toxicology, 1979
The absorption of radioactively labeled paraquat was measured in rat ileum, jejunum and colon by ... more The absorption of radioactively labeled paraquat was measured in rat ileum, jejunum and colon by a micro everted sac technique (Semenza and Mühlhaupt, 1969). The absorption rate increased linearly over the range of concentrations measured (10−5 to 10−2 M) and was enhanced by nearly 50% in the absence of sodium ions. The absorption rate decreased in the order: ileum, jejunum, colon whereby in the colon still 65% of the values of the small intestine were observed.
Archives of Toxicology, 1981
A case of severe sodium chlorate poisoning was observed within 5 h after suicidal ingestion of 15... more A case of severe sodium chlorate poisoning was observed within 5 h after suicidal ingestion of 150-200 g of the herbicide. Methaemoglobinaemia was the early symptom of the intoxication. Treatment with methylene blue and ascorbic acid could not prevent a massive haemolysis with disseminated intravascular coagulation. Hypercoagulation and hyperfibrinolysis could be treated successfully with exchange transfusions, heparin and flesh plasma. During the first hours, 70 mmol chlorate were excreted before complete renal failure occurred which required haemodialysis for several weeks. Clinical observations and in vitro experiments provide evidence that methylene blue is effective only in the very early stages of chlorate poisoning. Consequently, the following treatment is suggested: gastric lavage, exchange transfusion, bicarbonate infusion, haemodialysis, anticoagulation with heparin and substitution of clotting factors if necessary.
Archives of Toxicology, 1983
A method is presented that allows the measurement of erythrocyte filtration times that are extrem... more A method is presented that allows the measurement of erythrocyte filtration times that are extremely prolonged. Filtration times through polycarbonate sieves are increased by a factor of 40 after 2 h incubation with 30 mM sodium chlorate. This increase in red cell rigidity offers an explanation for the haemolysis observed in chlorate poisoning in vivo.
Toxicology, Jan 20, 2007
Clinical trials with antidotes are difficult to perform for a variety of practical, ethical, and ... more Clinical trials with antidotes are difficult to perform for a variety of practical, ethical, and financial reasons. As acute poisoning is a rare event, the commercial interest in basic and clinical research is low. Poisoned patients are usually not available for normal clinical trial procedures and, if they are, they cannot give informed consent. This situation results in a dilemma: antidotes are essential drugs. A resolution of the Council of Europe requests to guarantee the optimal availability of antidotes and the improvement of their use. As comprehensive data on the efficacy of antidotes are often missing, a marketing authorisation under exceptional circumstances according to Article 14(8) of Regulation (EC) No. 276/2004, will often be the only way to get an approval, as: (1) the indications for which the product in question is intended are encountered so rarely that the applicant cannot reasonably be expected to provide comprehensive evidence ("orphan drug"), (2) in ...
Journal of Clinical Pathology, 1983
Increased erythrocyte rigidity in chlorate Is guinea-pig inoculation ever justified for poisoning... more Increased erythrocyte rigidity in chlorate Is guinea-pig inoculation ever justified for poisoning the dianosis of tuberculosis?
Journal of Cardiovascular Pharmacology, 1995
We wished to determine whether chronic treatment of rats with cyclosporin A (CSA), an angiotensin... more We wished to determine whether chronic treatment of rats with cyclosporin A (CSA), an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor antagonists modulates the angiotensin receptor density. In rats treated chronically with CSA, the vasoconstrictor response to angiotensin II (AII) is increased and this increase is modulated by ACEI and angiotensin receptor antagonists. Rats were treated for 6 weeks orally with CSA (15 mg/kg/day), the ACE inhibitor lisinopril (10 mg/kg/day), the angiotensin receptor antagonists DUP 753 (10 mg/kg/day), and D 8731 (10 mg/kg/day) and the combinations CSA + lisinopril, CSA + DUP 753, and CSA + D 8731. Olive oil was used as a control. The number of total AII receptors (Bmax) was determined by Scatchard analysis of [125I]Sar1 Ile8 AII binding in kidney, liver, adrenal cortex, and adrenal medulla. The receptor subtypes were analyzed with the specific antagonists DUP 753 (subtype 1) and PD 123319 (subtype 2). CSA upregulated angiotensin receptors in all organs studied. Lisinopril alone downregulated angiotensin receptors and abolished the effect of CSA in liver and adrenal cortex and medulla, but not in the kidney, where it had no effect. DUP 753 alone downregulated the angiotensin receptor subtype 1 in kidney, liver and adrenal cortex; its effect on the adrenal medulla in which 89% of angiotensin receptors are subtype 2, did not quite reach significance. The combination of DUP 753 and cyclosporin CSA abolished the CSA-induced increase in angiotensin receptor density in all four organs. The angiotensin receptor antagonists D 8731 downregulated the angiotensin receptors (subtype 1) in liver and kidney and upregulated angiotensin receptors (subtype 2) in the adrenal medulla.(ABSTRACT TRUNCATED AT 250 WORDS)
NaunynSchmiedeberg's Archives of Pharmacology, 1980
Ethane evolution was measured in rats breathing pure oxygen. Animals injected i.p. with a lethal ... more Ethane evolution was measured in rats breathing pure oxygen. Animals injected i.p. with a lethal dose of paraquat (50 rng/kg) developed signs of pulmonary insufficiency within 3 hours and died within 24 hours. Ethane evolution, a parameter of lipid peroxldation in vlvo, was increased over control levels only by 26 % after 4 hours. It is concluded that this increase is too small to support the theory that lipid peroxidation is the biochemical mechanism of paraquat toxicity.
![Research paper thumbnail of Paraquat-induced formation of hydroperoxide in mouse liver microsomes [proceedings]](https://attachments.academia-assets.com/106301369/thumbnails/1.jpg)
](British journal of pharmacology, 1978
Toxicology and Applied Pharmacology, 1979
Liver microsomes from control and phenobarbital-induced (PB) mice have been used to study the eff... more Liver microsomes from control and phenobarbital-induced (PB) mice have been used to study the effect of paraquat (PQ) on oxygen reduction and malondialdehyde (MDA) formation. PQ increased the rate of NADPH-dependent oxygen uptake considerably in control and even more in PB-induced microsomes, but reduced the total amount of oxygen consumed, thus increasing the NAPDH/OI ratio from about unity to 2. This effect is not specific to PQ since menadione, electron acceptor for NADPH-cytochrome c-reductase, can produce the same phenomenon. Hydrogen peroxide was only a minor product in the unstimulated reaction, but accounted for all the oxygen consumed in the reaction stimulated by PQ. This was shown by methanol oxidation and after inhibition of catalase by sodium azide in vitro and by 2-amino-1,2,4-triazole (AT) in viuo. In contrast to previously published results lipid peroxidation as measured by MDA formation was not increased but rather inhibited by concentrations of PQ (K, 0.064 mM) lower than those needed to stimulate oxygen uptake (K,,, 0.60 mhi) and to inhibit p-nitroanisole-0-demethylation (K, 0.58 mM). The IO-fold concentration difference suggests different mechanisms for the action of PQ in these processes. This observation does not favor the concept of lipid peroxidation as the mechanism of PQ toxicity.
European Journal of Drug Metabolism and Pharmacokinetics, 1984
A kinetic evaluation of 14C0 2 in expired air after 14C-methacetin administration in rats, used f... more A kinetic evaluation of 14C0 2 in expired air after 14C-methacetin administration in rats, used for the study of the metabolism of drugs
Red yeast rice (i.e., rice fermented with Monascus spp.) is currently sold via the Internet as a ... more Red yeast rice (i.e., rice fermented with Monascus spp.) is currently sold via the Internet as a dietary supplement. Claims state that red yeast rice has the ability to lower blood cholesterol concentrations. The mechanism of action is well characterised because the red yeast rice constituent monacolin K is identical with lovastatin, an inhibitor of the hydroxymethylglutaryl-CoA (HMG-CoA) reductase that is used in many cholesterol-lowering medicinal products. The aim of this article is to evaluate the properties of red yeast rice products that are marketed via the Internet. Three out of five analyzed products may reach the daily dosage of 10 mg lovastatin, which is necessary for the substantiation of health claims on the maintenance of normal blood LDL-cholesterol levels as suggested by the Scientific Opinion of the European Food Safety Authority. 10 mg is also the starting dosage of medicinal lovastatin products on the German market. From a regulatory standpoint, red yeast rice pro...
Zeitschrift für Naturforschung C, 1979
Catalase (E. C. 1.11.1.6) activity and NADPH-depen-dent lipid peroxidation have been measured in ... more Catalase (E. C. 1.11.1.6) activity and NADPH-depen-dent lipid peroxidation have been measured in liver micro somes from normal and acatalasemic mice. The absence of lipid peroxidation in acatalatic microsomes is not restituted by exogenous catalase as is microsomal methanol oxidation nor is it inhibited by sodium azide, thus suggesting an additional abnormality in these mice.
Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz, Jan 4, 2017
Red yeast rice is the fermentation product of the mould Monascus ruber and is traditionally used ... more Red yeast rice is the fermentation product of the mould Monascus ruber and is traditionally used in East Asia to dye and conserve food. Its main pharmacologically active compound, monakolin K, was isolated from red yeast rice and is used as an inhibitor of cholesterol synthesis under the INN lovastatin. Lovastatin and several other statins are marketed as drugs whereas red yeast rice is offered as a food supplement. As statins can cause severe side effects, such as muscle damage and kidney failure, the dosing and information about interactions with drugs and food is essential for the use of these products. Furthermore, red yeast rice can contain the mycotoxin citrinin and several other substances that are not yet toxicologically evaluated.
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz, 2006
Zusammenfassung In vitro durchgefhrte experimentelle Untersuchungen konnten nachweisen, dass ein... more Zusammenfassung In vitro durchgefhrte experimentelle Untersuchungen konnten nachweisen, dass einzelne Pathomechanismen der Atherosklerose durch Antioxidantien (z. B. β-Carotin, Vitamin C und Vitamin E) gnstig beeinflusst werden knnen, wobei Vitamin E die deutlichsten Effekte aufwies. Tierexperimentell und in einer Reihe epidemiologischer Studien konnte ein protektiver Effekt von Vitamin E insbesondere unter Verabreichung hoher Dosen nachgewiesen werden. Demgegenber zeigten die meisten der zur primren und sekundren Prvention durchgefhrten placebokontrollierten Studien selbst bei Verabreichung hoher Dosen keinen relevanten protektiven Effekt einer Supplementierung von Antioxidantien (insbesondere von Vitamin E). Darber hinaus wiesen einzelne Untersuchungen auch auf mgliche Nebenwirkungen einer Supplementierung hin. Die vorliegende Arbeit liefert einen berblick ber das Prinzip der Supplementierung von Antioxidantien insbesondere unter Verwendung von Vitamin E und beschreibt die Ergebnisse zahlreicher epidemiologischer und klinischer Studien zur Prvention atherosklerotischer Geferkrankungen. Sie kommt zu dem Ergebnis, dass eine Supplementierung in der Normalbevlkerung derzeit nicht empfohlen werden kann.
Toxicology, 1993
Intoxications with chlorate salts are characterized by methaemoglobin formation, haemolysis and r... more Intoxications with chlorate salts are characterized by methaemoglobin formation, haemolysis and renal insufficiency. The toxic effects on the erythrocyte can be reproduced in vitro. Incubation of human and rabbit erythrocytes with chlorates induces a concentration-dependent oxidation of haemoglobin. This methaemoglobin formation is followed by denaturation of the globin, a cross-linking of erythrocyte membrane proteins and an inactivation of membrane enzymes. The high sensitivity of glucose-6-phosphate dehydrogenase to denaturation by chlorate explains the inefficacy of methylene blue to reduce methaemoglobin formed, as the antidotal effect of methylene blue depends on NADPH formed mainly by the oxidation of glucose-6-phosphate. The observed changes occur only in the presence of methaemoglobin which forms a destabilising complex with chlorate. Methaemoglobin thus autocatalytically increases methaemoglobin formation and destruction of the erythrocyte. As the rabbit is known to have a high methaemoglobin-reduction capacity, human and rabbit erythrocytes were compared. In vitro, the rabbit erythrocyte is less sensitive to oxidative attack than the human red cell. In vivo, an oral dose of sodium chlorate (1 g/kg body wt.) resulted in high serum (16 +/- 4 mM) and urine concentrations (246 +/- 99 mM) in the rabbit. Methaemoglobin was not formed nor could a nephrotoxic effect be observed. These experiments also indicate that the nephrotoxicity of chlorate is mediated by methaemoglobin catalysis.
RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2010
Human Toxicology, 1985
Relle et al., 1984). Reduction in the intracellular content of glutathione was achieved by nutrit... more Relle et al., 1984). Reduction in the intracellular content of glutathione was achieved by nutritional deprivation of L-cysteine or by exposure of cells to D,L-buthionine-S,R-sulphoximine (BSO), a potent inhibitor of y-glutamylcysteine synthetase, and was accompanied by sensitization of melphalan-resistant L1210 cells. We have investigated the effect of BSO on glutathione levels in two types of human leukaemia cells: (1) K562 human chronic myeloid leukaemia cell line; (ii) primary isolates of cyclophosphamide (CP)-resistant chronic lymphocytic leukaemia (CLL) cells. K562 and primary CLL isolates were exposed to BSO at concentrations of 1-500 Rm for 0-24 h periods (three experiments). Glutathione was determined by the Griffith (1980) enzymic recycling method, based on glutathione reductase, as modified by Suzukake et al. (1982). A maximal reduction of approximately 60% in cellular glutathione content was achieved in mid-late log-phase K562 cells and primary CLL isolates by exposure to 50 u,M-BSO for 20 h. This treatment had no effect on cell viability and caused only a slight reduction in colonyforming ability in K562 cells. K562 cells depleted of glutathione were exposed to hepatocyte-activated CP for 1 h and cytotoxicity measured by proliferation and colony-forming assays as described previously (Crook et al., 1985). These cells displayed a very marked increase in sensitivity to CP (Table 1). Moreover, loss of viability was evident as early as 3 h after drug exposure in glutathione-depleted cells but much later in control cells exposed to a CP dose having the same final cytotoxicity. This suggests a separate mechanism of toxicity of CP in glutathione-depleted cells.
Biochemical Pharmacology, 1985
Archives of Toxicology, 1979
The absorption of radioactively labeled paraquat was measured in rat ileum, jejunum and colon by ... more The absorption of radioactively labeled paraquat was measured in rat ileum, jejunum and colon by a micro everted sac technique (Semenza and Mühlhaupt, 1969). The absorption rate increased linearly over the range of concentrations measured (10−5 to 10−2 M) and was enhanced by nearly 50% in the absence of sodium ions. The absorption rate decreased in the order: ileum, jejunum, colon whereby in the colon still 65% of the values of the small intestine were observed.
Archives of Toxicology, 1981
A case of severe sodium chlorate poisoning was observed within 5 h after suicidal ingestion of 15... more A case of severe sodium chlorate poisoning was observed within 5 h after suicidal ingestion of 150-200 g of the herbicide. Methaemoglobinaemia was the early symptom of the intoxication. Treatment with methylene blue and ascorbic acid could not prevent a massive haemolysis with disseminated intravascular coagulation. Hypercoagulation and hyperfibrinolysis could be treated successfully with exchange transfusions, heparin and flesh plasma. During the first hours, 70 mmol chlorate were excreted before complete renal failure occurred which required haemodialysis for several weeks. Clinical observations and in vitro experiments provide evidence that methylene blue is effective only in the very early stages of chlorate poisoning. Consequently, the following treatment is suggested: gastric lavage, exchange transfusion, bicarbonate infusion, haemodialysis, anticoagulation with heparin and substitution of clotting factors if necessary.
Archives of Toxicology, 1983
A method is presented that allows the measurement of erythrocyte filtration times that are extrem... more A method is presented that allows the measurement of erythrocyte filtration times that are extremely prolonged. Filtration times through polycarbonate sieves are increased by a factor of 40 after 2 h incubation with 30 mM sodium chlorate. This increase in red cell rigidity offers an explanation for the haemolysis observed in chlorate poisoning in vivo.
Toxicology, Jan 20, 2007
Clinical trials with antidotes are difficult to perform for a variety of practical, ethical, and ... more Clinical trials with antidotes are difficult to perform for a variety of practical, ethical, and financial reasons. As acute poisoning is a rare event, the commercial interest in basic and clinical research is low. Poisoned patients are usually not available for normal clinical trial procedures and, if they are, they cannot give informed consent. This situation results in a dilemma: antidotes are essential drugs. A resolution of the Council of Europe requests to guarantee the optimal availability of antidotes and the improvement of their use. As comprehensive data on the efficacy of antidotes are often missing, a marketing authorisation under exceptional circumstances according to Article 14(8) of Regulation (EC) No. 276/2004, will often be the only way to get an approval, as: (1) the indications for which the product in question is intended are encountered so rarely that the applicant cannot reasonably be expected to provide comprehensive evidence ("orphan drug"), (2) in ...
Journal of Clinical Pathology, 1983
Increased erythrocyte rigidity in chlorate Is guinea-pig inoculation ever justified for poisoning... more Increased erythrocyte rigidity in chlorate Is guinea-pig inoculation ever justified for poisoning the dianosis of tuberculosis?
Journal of Cardiovascular Pharmacology, 1995
We wished to determine whether chronic treatment of rats with cyclosporin A (CSA), an angiotensin... more We wished to determine whether chronic treatment of rats with cyclosporin A (CSA), an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor antagonists modulates the angiotensin receptor density. In rats treated chronically with CSA, the vasoconstrictor response to angiotensin II (AII) is increased and this increase is modulated by ACEI and angiotensin receptor antagonists. Rats were treated for 6 weeks orally with CSA (15 mg/kg/day), the ACE inhibitor lisinopril (10 mg/kg/day), the angiotensin receptor antagonists DUP 753 (10 mg/kg/day), and D 8731 (10 mg/kg/day) and the combinations CSA + lisinopril, CSA + DUP 753, and CSA + D 8731. Olive oil was used as a control. The number of total AII receptors (Bmax) was determined by Scatchard analysis of [125I]Sar1 Ile8 AII binding in kidney, liver, adrenal cortex, and adrenal medulla. The receptor subtypes were analyzed with the specific antagonists DUP 753 (subtype 1) and PD 123319 (subtype 2). CSA upregulated angiotensin receptors in all organs studied. Lisinopril alone downregulated angiotensin receptors and abolished the effect of CSA in liver and adrenal cortex and medulla, but not in the kidney, where it had no effect. DUP 753 alone downregulated the angiotensin receptor subtype 1 in kidney, liver and adrenal cortex; its effect on the adrenal medulla in which 89% of angiotensin receptors are subtype 2, did not quite reach significance. The combination of DUP 753 and cyclosporin CSA abolished the CSA-induced increase in angiotensin receptor density in all four organs. The angiotensin receptor antagonists D 8731 downregulated the angiotensin receptors (subtype 1) in liver and kidney and upregulated angiotensin receptors (subtype 2) in the adrenal medulla.(ABSTRACT TRUNCATED AT 250 WORDS)
NaunynSchmiedeberg's Archives of Pharmacology, 1980
Ethane evolution was measured in rats breathing pure oxygen. Animals injected i.p. with a lethal ... more Ethane evolution was measured in rats breathing pure oxygen. Animals injected i.p. with a lethal dose of paraquat (50 rng/kg) developed signs of pulmonary insufficiency within 3 hours and died within 24 hours. Ethane evolution, a parameter of lipid peroxldation in vlvo, was increased over control levels only by 26 % after 4 hours. It is concluded that this increase is too small to support the theory that lipid peroxidation is the biochemical mechanism of paraquat toxicity.
British journal of pharmacology, 1978
Toxicology and Applied Pharmacology, 1979
Liver microsomes from control and phenobarbital-induced (PB) mice have been used to study the eff... more Liver microsomes from control and phenobarbital-induced (PB) mice have been used to study the effect of paraquat (PQ) on oxygen reduction and malondialdehyde (MDA) formation. PQ increased the rate of NADPH-dependent oxygen uptake considerably in control and even more in PB-induced microsomes, but reduced the total amount of oxygen consumed, thus increasing the NAPDH/OI ratio from about unity to 2. This effect is not specific to PQ since menadione, electron acceptor for NADPH-cytochrome c-reductase, can produce the same phenomenon. Hydrogen peroxide was only a minor product in the unstimulated reaction, but accounted for all the oxygen consumed in the reaction stimulated by PQ. This was shown by methanol oxidation and after inhibition of catalase by sodium azide in vitro and by 2-amino-1,2,4-triazole (AT) in viuo. In contrast to previously published results lipid peroxidation as measured by MDA formation was not increased but rather inhibited by concentrations of PQ (K, 0.064 mM) lower than those needed to stimulate oxygen uptake (K,,, 0.60 mhi) and to inhibit p-nitroanisole-0-demethylation (K, 0.58 mM). The IO-fold concentration difference suggests different mechanisms for the action of PQ in these processes. This observation does not favor the concept of lipid peroxidation as the mechanism of PQ toxicity.
European Journal of Drug Metabolism and Pharmacokinetics, 1984
A kinetic evaluation of 14C0 2 in expired air after 14C-methacetin administration in rats, used f... more A kinetic evaluation of 14C0 2 in expired air after 14C-methacetin administration in rats, used for the study of the metabolism of drugs
Red yeast rice (i.e., rice fermented with Monascus spp.) is currently sold via the Internet as a ... more Red yeast rice (i.e., rice fermented with Monascus spp.) is currently sold via the Internet as a dietary supplement. Claims state that red yeast rice has the ability to lower blood cholesterol concentrations. The mechanism of action is well characterised because the red yeast rice constituent monacolin K is identical with lovastatin, an inhibitor of the hydroxymethylglutaryl-CoA (HMG-CoA) reductase that is used in many cholesterol-lowering medicinal products. The aim of this article is to evaluate the properties of red yeast rice products that are marketed via the Internet. Three out of five analyzed products may reach the daily dosage of 10 mg lovastatin, which is necessary for the substantiation of health claims on the maintenance of normal blood LDL-cholesterol levels as suggested by the Scientific Opinion of the European Food Safety Authority. 10 mg is also the starting dosage of medicinal lovastatin products on the German market. From a regulatory standpoint, red yeast rice pro...
Zeitschrift für Naturforschung C, 1979
Catalase (E. C. 1.11.1.6) activity and NADPH-depen-dent lipid peroxidation have been measured in ... more Catalase (E. C. 1.11.1.6) activity and NADPH-depen-dent lipid peroxidation have been measured in liver micro somes from normal and acatalasemic mice. The absence of lipid peroxidation in acatalatic microsomes is not restituted by exogenous catalase as is microsomal methanol oxidation nor is it inhibited by sodium azide, thus suggesting an additional abnormality in these mice.
Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz, Jan 4, 2017
Red yeast rice is the fermentation product of the mould Monascus ruber and is traditionally used ... more Red yeast rice is the fermentation product of the mould Monascus ruber and is traditionally used in East Asia to dye and conserve food. Its main pharmacologically active compound, monakolin K, was isolated from red yeast rice and is used as an inhibitor of cholesterol synthesis under the INN lovastatin. Lovastatin and several other statins are marketed as drugs whereas red yeast rice is offered as a food supplement. As statins can cause severe side effects, such as muscle damage and kidney failure, the dosing and information about interactions with drugs and food is essential for the use of these products. Furthermore, red yeast rice can contain the mycotoxin citrinin and several other substances that are not yet toxicologically evaluated.