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Age-associated inhibition of renal and hepatic Mg2+-ATPase activity by factors known to affect mixed function oxidase (MFO) system
Book of Abstmcts- EUROTOX ‘94
16 Age-Associated Inhibition of Renal and Hepatlc Affect WhrcedFunction Oxidase (MFO) System f?Czekai.
G. Nowaczyk-Dura.
A. Plewka.
II Department
of
Mg
*+-ATPase Activity by Factors Known to
Histology and Embryology. Silesian MedicalAcademH
Kktowice. Poland The main purpose of this study was to elucidate the effect of age, beta-naphthoflavone (DM) on Mg*+-ATPase which is thought to be related to the membrane transport.
(BNF), and dexamethasone
The experiments were carried out on 0.5-. l-. 2-. 4-. 8-. 12-. 20-. and 28-months old Wistar males rats. The animals of the treated groups were injected once daily for 3 days with BNF - 20 mg/kg. or DM - 10 mg/kg. Mg*+-ATPase was determined according to the method of Wachstein and Meisel. The activity of the examined enzymatic reactions were carried by densitometric measurements. The pattern of age-dependent changes of renal and hepatic Mg *+-ATPase activities was similar. Between 0.5-l month of postnatal life there was observed an increase of activity to a level that was not significantly altered until 4 months (in the liver). or decreased slightly (in the kidney). The increase of activity was again observed (in both organs) in 8 month old rats to a level that was maintained until 28-months age. BNF and DM -typical MFO inducers - inhibited the transport enzyme - Mg *+-ATPase, in all investigated age groups by 59% and 46%. respectively -
in the liver. and by 56% and 43%.
the inducers that stimulate biotransformation
respectively
-
in the kidney. Thus,
of xenobiotics can inhibit other enzymatic activities during the young,
adult or old life of rats. Key words:
Mg*+-ATPase;
beta-naphthoflavone;
dexamethasone:
age; rats
Teratogenic Activity of Tketinoin in the Giittingen Mini-Pig K. Damm Jaroensen. Scantox, Denmark Retinoic acid has been shown to be teratogenic in mice. rats, hamsters,
monkeys and man. In the present study
the teratogenic activity of all-trans retinoic acid (tretinoin) was assessed in the mini-pig. Groups of 4-7 mini-pigs (gilts) were given tretinoin in doses of 3. 10 and 20 mg/kg p.o. in oleum arachidis through day 11 to day 35 incl. of gestation. Only four mini-pigs were given 20 mg/kg. as this dose level proved to have a marked toxicity. A control group of 5 mini-pigs was given oleum arachidis. Pregnancy was verified by ultrasonography 3-4 weeks after mating. The dams and foetuses were autopsied on day 110-l 11 of pregnancy and skeletal examinations of the foetuses were performed using both X-ray and alizarin staining. Dose-dependent maternal toxicity was seen In all dose groups. The adverse clinical signs comprised erythema. eczema and dermatitis. depression and anorexia. Two mini-pigs given 20 mg/kg died and one had to be sacrificed. One mlnl-pig given 10 mg/kg died from cardiac Insufficiency. Only early resorptions occurred in the group given 20 mgkg.
In the group given 10 mglkg multiple major malformations
were seen such as agenesis or hypogenesis of
radius and ulna. tibia arbd fibuia. ectrodactyly, cleft palate. gastroschisis. gall bladder agenesis. atresia ani and tetralogy of Fallot. In the group given 3 mg/kg minor malformations such as polydactyly and muscular-joint contractures were seen. The susceptibility of the mini-pig to the teratogenic effects of tretinoin is similar to that reported for pigtail monkeys with respect to types of malformations
as well as teratogenic
potency.
Alterations of lnterdigitating Dendritic Cells in the Rat Thymus During Cyclosporin A Treatment and Recovery E.J. De Waal’,
H.-J. Schuurman 3, J.G. Vos ‘, H. Van Loveren Protection, Bilthoven, lhe Netherlands; 2 Department
L.H.i?M. Rademakers*,
Public Health and Environmental
Hospital. Utrecht. The Netherlands;
‘. ’ National institute of of Pathology. University
3 Preclinical Research, Sandoz Pharma Ltd. BaseI, Switzerland
in the normal rat thymus. interdigitating
dendritic cells (IDC) are involved in antigen presentation
and clonal dele-
tion of autoreactive thymocytes. After cyclosporin A (CsA) treatment, IDC disappear. Related to this action, CsA administration can result in the release of autoreactive thymocytes to the periphery. We pet-formed a quantitative ultrastructural
study on the rat thymic IDC population Juring CsA treatment
and recovery
Male Wistar rats were
injected intravenously with 7.5 mg CsA/kg body weight once daily for 14 days. Animals were sacrificed during treatment and subsequent criteria.
B-week recovery, respectively. Classification of IDC subtypes was based on ultrastructural
During CsA treatment.
a prominent reduction of IDC was seen in the medulla. The number of mature IDC de-
clined later than the number “f immature ones. A decrease in the antigen-presenting
capacity of remaining IDC was
suggested by disappearance of Birbeck granules and loss of tubulovesicular complexes. These findings support a disturbance of clonal deletion during CsA treatment. The IDC alterations appeared reversible first on day 41 of recovery. i.e. four weeks after the restoration of the original architecture.
During recovery, IDC displaying lysoso-
16 Age-Associated Inhibition of Renal and Hepatlc Affect WhrcedFunction Oxidase (MFO) System f?Czekai.
G. Nowaczyk-Dura.
A. Plewka.
II Department
of
Mg
*+-ATPase Activity by Factors Known to
Histology and Embryology. Silesian MedicalAcademH
Kktowice. Poland The main purpose of this study was to elucidate the effect of age, beta-naphthoflavone (DM) on Mg*+-ATPase which is thought to be related to the membrane transport.
(BNF), and dexamethasone
The experiments were carried out on 0.5-. l-. 2-. 4-. 8-. 12-. 20-. and 28-months old Wistar males rats. The animals of the treated groups were injected once daily for 3 days with BNF - 20 mg/kg. or DM - 10 mg/kg. Mg*+-ATPase was determined according to the method of Wachstein and Meisel. The activity of the examined enzymatic reactions were carried by densitometric measurements. The pattern of age-dependent changes of renal and hepatic Mg *+-ATPase activities was similar. Between 0.5-l month of postnatal life there was observed an increase of activity to a level that was not significantly altered until 4 months (in the liver). or decreased slightly (in the kidney). The increase of activity was again observed (in both organs) in 8 month old rats to a level that was maintained until 28-months age. BNF and DM -typical MFO inducers - inhibited the transport enzyme - Mg *+-ATPase, in all investigated age groups by 59% and 46%. respectively -
in the liver. and by 56% and 43%.
the inducers that stimulate biotransformation
respectively
-
in the kidney. Thus,
of xenobiotics can inhibit other enzymatic activities during the young,
adult or old life of rats. Key words:
Mg*+-ATPase;
beta-naphthoflavone;
dexamethasone:
age; rats
Teratogenic Activity of Tketinoin in the Giittingen Mini-Pig K. Damm Jaroensen. Scantox, Denmark Retinoic acid has been shown to be teratogenic in mice. rats, hamsters,
monkeys and man. In the present study
the teratogenic activity of all-trans retinoic acid (tretinoin) was assessed in the mini-pig. Groups of 4-7 mini-pigs (gilts) were given tretinoin in doses of 3. 10 and 20 mg/kg p.o. in oleum arachidis through day 11 to day 35 incl. of gestation. Only four mini-pigs were given 20 mg/kg. as this dose level proved to have a marked toxicity. A control group of 5 mini-pigs was given oleum arachidis. Pregnancy was verified by ultrasonography 3-4 weeks after mating. The dams and foetuses were autopsied on day 110-l 11 of pregnancy and skeletal examinations of the foetuses were performed using both X-ray and alizarin staining. Dose-dependent maternal toxicity was seen In all dose groups. The adverse clinical signs comprised erythema. eczema and dermatitis. depression and anorexia. Two mini-pigs given 20 mg/kg died and one had to be sacrificed. One mlnl-pig given 10 mg/kg died from cardiac Insufficiency. Only early resorptions occurred in the group given 20 mgkg.
In the group given 10 mglkg multiple major malformations
were seen such as agenesis or hypogenesis of
radius and ulna. tibia arbd fibuia. ectrodactyly, cleft palate. gastroschisis. gall bladder agenesis. atresia ani and tetralogy of Fallot. In the group given 3 mg/kg minor malformations such as polydactyly and muscular-joint contractures were seen. The susceptibility of the mini-pig to the teratogenic effects of tretinoin is similar to that reported for pigtail monkeys with respect to types of malformations
as well as teratogenic
potency.
Alterations of lnterdigitating Dendritic Cells in the Rat Thymus During Cyclosporin A Treatment and Recovery E.J. De Waal’,
H.-J. Schuurman 3, J.G. Vos ‘, H. Van Loveren Protection, Bilthoven, lhe Netherlands; 2 Department
L.H.i?M. Rademakers*,
Public Health and Environmental
Hospital. Utrecht. The Netherlands;
‘. ’ National institute of of Pathology. University
3 Preclinical Research, Sandoz Pharma Ltd. BaseI, Switzerland
in the normal rat thymus. interdigitating
dendritic cells (IDC) are involved in antigen presentation
and clonal dele-
tion of autoreactive thymocytes. After cyclosporin A (CsA) treatment, IDC disappear. Related to this action, CsA administration can result in the release of autoreactive thymocytes to the periphery. We pet-formed a quantitative ultrastructural
study on the rat thymic IDC population Juring CsA treatment
and recovery
Male Wistar rats were
injected intravenously with 7.5 mg CsA/kg body weight once daily for 14 days. Animals were sacrificed during treatment and subsequent criteria.
B-week recovery, respectively. Classification of IDC subtypes was based on ultrastructural
During CsA treatment.
a prominent reduction of IDC was seen in the medulla. The number of mature IDC de-
clined later than the number “f immature ones. A decrease in the antigen-presenting
capacity of remaining IDC was
suggested by disappearance of Birbeck granules and loss of tubulovesicular complexes. These findings support a disturbance of clonal deletion during CsA treatment. The IDC alterations appeared reversible first on day 41 of recovery. i.e. four weeks after the restoration of the original architecture.
During recovery, IDC displaying lysoso-