maternal diets and early environmental exposure influences weight maintenance and development of the...

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Abstracts / Toxicology Letters 172S (2007) S1–S240 S189 sis of Alzheimer’s disease (AD), which is characterized by progressive decline of cognitive function, formation of A beta plaques, and neurofibrillary trangles, and loss of neurons. In the present study we have examined that treatment by vitamin E + Statin in PDAPP aged mice compared with control groups is able to decrease 20% in AB plaques levels of cerebral amyloidosis in necortex. More- over, our results suggest that treatment by vitamins is able to prevent the disruption of basal cholinergic fore- brain system and prevent of loss of cholinergic basal forebrain neurons (Ms + HDB, VDB). doi:10.1016/j.toxlet.2007.05.477 D29 Maternal diets and early environmental exposure influences weight maintenance and development of the offspring Andr´ e Wolterbeek , Simone Eussen, Renate Jansink, Linda van der Horst, Marlies Otto, Ine Waalkens, Anja Dijkstra, Florence Salmon, Heleen Wortelboer, Wilrike Pasman, Henk Hendriks, Ivana Bobeldijk, Didima de Groot TNO Quality of Life, Zeist, Netherlands Obesity and related diseases are major threats to health in western societies. To study (1) the impact of maternal diets on body weight of the offspring and (2) the effects of maternal diets in combination with environmental exposure on the (neuro)development of the offspring, three groups of female Wistar rats (n = 28–32) were kept on a con- trol diet, a western style type diet or a deficient diet during 6 weeks premating, mating, gestation and lac- tation. On postnatal day 1 (PN 1) the F1-pups were cross-fostered to dams of the same group or to dams of the other two dietary groups to obtain nine different groups. F1-pups were fed the various diets up to PN 70 and body weight/mass and food intake were mea- sured regularly. To investigate environmental influences, the vulnerability for chemically induced neurotoxicity F1-pups were treated subcutaneously with MAM (from PN day 2 to 5, twice daily) or MeHg (from PN 2 to 21). The results showed that: (1) Food consumption, energy intake and body weights of the dams differed significantly between the groups. (2) Birth weight of the pups of dams on a deficient diet were slightly, not signif- icantly, decreased. (3) Dietary habits during premating and gestation phases appeared to influence the growth of the pups during lactation, showing ‘catch-up’ growth of the deficient pups fostered to dams on the western style type diet and, vice-versa, decreased growth of the western style type diet pups fostered to dams on a defi- cient diet. Dietary induced effects on body weights of F1 animals were exacerbated by exposure to MAM or MeHg. It was concluded that maternal diet manipulation had (transitory) effects on the offspring which, in turn, may be responsible for increased vulnerability of the off- spring for (subtle) environmental influences at or shortly after birth causing life-long developmental effects. doi:10.1016/j.toxlet.2007.05.478 P11 Food Safety F01 Ochratoxin A-induced renal gene expression changes in F344 rats after repeated oral administration Leire Arbillaga , Ariane Vettorazzi, Ana G. Gil, Adela opez de Cerain Department of Food Sciences, Physiology and Toxicology, Faculty of Pharmacy, University of Navarra, Pamplona, Navarra, Spain Ochratoxin A (OTA) is a nephrotoxic mycotoxin often found in agricultural products. There is unequivocal evi- dence of renal carcinogenicity in male rats although its mechanism of action is unknown. Direct genotoxicity versus epigenetic mechanisms are still under debate. The most recent data based on biochemical and toxicoge- nomic evidence, indicate that chronic administration of a carcinogenic dose of OTA results in a significant reduc- tion of renal antioxidant defence and increased oxidative DNA damage. This study has been designed to analyze renal gene expression changes in F344 rats after repeated oral car- cinogenic dose of OTA dissolved in 0.1 M NaHCO 3 pH 7.4. For this purpose, 0.5mg/kg bw OTA was adminis- tered daily by gavage to two groups (n = 5) of male F344 rats and gene expression modulation was studied at 7 and 21 days. Two control vehicles of five animals were also included in order to compare the gene expression pat- tern of each treated group with its corresponding control. Affymetrix Rat Genome 230 2.0 Gene Chips containing 28.000 well-substantiated rat genes, were used. Modu- lated genes were identified using BRB-ArrayTools and classified in biological pathways using GenMapp. Histopathological and biochemical data showed slight signs of nephrotoxicity. These findings will be

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Abstracts / Toxicology

is of Alzheimer’s disease (AD), which is characterizedy progressive decline of cognitive function, formationf A beta plaques, and neurofibrillary trangles, and lossf neurons.

In the present study we have examined that treatmenty vitamin E + Statin in PDAPP aged mice comparedith control groups is able to decrease 20% in ABlaques levels of cerebral amyloidosis in necortex. More-ver, our results suggest that treatment by vitamins isble to prevent the disruption of basal cholinergic fore-rain system and prevent of loss of cholinergic basalorebrain neurons (Ms + HDB, VDB).

oi:10.1016/j.toxlet.2007.05.477

29aternal diets and early environmental exposure

nfluences weight maintenance and development ofhe offspring

ndre Wolterbeek, Simone Eussen, Renate Jansink,inda van der Horst, Marlies Otto, Ine Waalkens, Anjaijkstra, Florence Salmon, Heleen Wortelboer,ilrike Pasman, Henk Hendriks, Ivana Bobeldijk,idima de Groot

TNO Quality of Life, Zeist, Netherlands

besity and related diseases are major threats to healthn western societies.

To study (1) the impact of maternal diets on bodyeight of the offspring and (2) the effects of maternaliets in combination with environmental exposure onhe (neuro)development of the offspring, three groupsf female Wistar rats (n = 28–32) were kept on a con-rol diet, a western style type diet or a deficient dieturing 6 weeks premating, mating, gestation and lac-ation. On postnatal day 1 (PN 1) the F1-pups wereross-fostered to dams of the same group or to damsf the other two dietary groups to obtain nine differentroups. F1-pups were fed the various diets up to PN0 and body weight/mass and food intake were mea-ured regularly. To investigate environmental influences,he vulnerability for chemically induced neurotoxicity1-pups were treated subcutaneously with MAM (fromN day 2 to 5, twice daily) or MeHg (from PN 2

o 21).The results showed that: (1) Food consumption,

nergy intake and body weights of the dams differed

ignificantly between the groups. (2) Birth weight of theups of dams on a deficient diet were slightly, not signif-cantly, decreased. (3) Dietary habits during prematingnd gestation phases appeared to influence the growth

172S (2007) S1–S240 S189

of the pups during lactation, showing ‘catch-up’ growthof the deficient pups fostered to dams on the westernstyle type diet and, vice-versa, decreased growth of thewestern style type diet pups fostered to dams on a defi-cient diet. Dietary induced effects on body weights ofF1 animals were exacerbated by exposure to MAM orMeHg.

It was concluded that maternal diet manipulation had(transitory) effects on the offspring which, in turn, maybe responsible for increased vulnerability of the off-spring for (subtle) environmental influences at or shortlyafter birth causing life-long developmental effects.

doi:10.1016/j.toxlet.2007.05.478

P11 Food Safety

F01Ochratoxin A-induced renal gene expressionchanges in F344 rats after repeated oraladministration

Leire Arbillaga, Ariane Vettorazzi, Ana G. Gil, AdelaLopez de Cerain

Department of Food Sciences, Physiology andToxicology, Faculty of Pharmacy, University ofNavarra, Pamplona, Navarra, Spain

Ochratoxin A (OTA) is a nephrotoxic mycotoxin oftenfound in agricultural products. There is unequivocal evi-dence of renal carcinogenicity in male rats although itsmechanism of action is unknown. Direct genotoxicityversus epigenetic mechanisms are still under debate. Themost recent data based on biochemical and toxicoge-nomic evidence, indicate that chronic administration ofa carcinogenic dose of OTA results in a significant reduc-tion of renal antioxidant defence and increased oxidativeDNA damage.

This study has been designed to analyze renal geneexpression changes in F344 rats after repeated oral car-cinogenic dose of OTA dissolved in 0.1 M NaHCO3 pH7.4. For this purpose, 0.5 mg/kg bw OTA was adminis-tered daily by gavage to two groups (n = 5) of male F344rats and gene expression modulation was studied at 7 and21 days. Two control vehicles of five animals were alsoincluded in order to compare the gene expression pat-tern of each treated group with its corresponding control.Affymetrix Rat Genome 230 2.0 Gene Chips containing28.000 well-substantiated rat genes, were used. Modu-

lated genes were identified using BRB-ArrayTools andclassified in biological pathways using GenMapp.

Histopathological and biochemical data showedslight signs of nephrotoxicity. These findings will be