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Immunostimulating lipopeptide, LtriP (RP 56142): Comparison of the effect on hepatic cytochrome P 450 modulation and radioprotection in male and female of three mouse strains

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Abstract

The sex-dependent effect of lauroyl-L-Ala-D-γ-Glu-L,L-A2pmNH2 (LtriP, RP 56142) on hepatic microsomal cytochromes P 450 (cyt P 450) was studied in three mouse strains NMRI, C3H/OuJ and C3H/HeJ. In NMRI and C3H/OuJ, strains which are responsive to bacterial lipopolysaccharides (LPS-responsive), regardless of the sex of the mouse, significant decrease in the amount of cyt P 450 was observed after LtriP treatment, with a concomitant reduction in ethoxyresorufin-O-deethylase (cyt P 450 1A-dependent) and 7-ethoxycoumarin-O-deethylase activities. This was not seen in C3H/HeJ (LPS-hyporesponsive) mice. These effects may be related to LtriP-dependent cytokine induction, since neither LtriP nor LPS stimulated interleukin-1 (IL-1) secretion by C3H/HeJ macrophages. 11- and 12-hydroxylations (11- and 12-OH) of lauric acid were compared in C3H/OuJ and C3H/HeJ mice. LtriP depressed the total enzymatic conversion of lauric acid in the two strains without modification of the 11/12-OH ratio for C3H/OuJ or male C3H/HeJ mice. However, in females C3H/HeJ mice this decrease was particularly significant and concerned especially the 12-OH activity (a marker of cyt P450 4A family). Although males of the three strains were more sensitive to irradiation than females, LtriP exerted a sex-independent radioprotection on NMRI and C3H/OuJ mice. Its radioprotective effect was illustrated by the preservation of all the enzymatic activities studied in treated NMRI mice, contrary to irradiated control animals. In contrast, for the C3H/HeJ strain, males were not protected by LtriP treatment and, furthermore, females showed a marked sensitization to irradiation.

The effects in CH3/HeJ strain implicate LtriP in the control of cyt P 450 induction and of sensitivity to irradiation independently of IL-1 induction.

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Abbreviations

A 2 pm :

diaminopimelic acid

BCG :

Bacillus Calmette Guerin

B.R.O.D. :

benzyloxyresorufin-O-dealkylase

cyt :

cytochrome

DMSO :

dimethylsulfoxide

7-E.C. :

7-ethoxycoumarin-O-deethylase

EDTA :

ethylenediaminetetraacetic acid

E.R.O.D. :

ethoxyresorufin-O-deethylase

IL-1 :

interleukin-1

i.p. :

intraperitoneal

LPS :

lipopolysaccharide or endotoxin

LtriP :

lauroyltripeptide

M-CSF :

macrophage-colony stimulating factor

MDA :

malondialdehyde

NADPH :

reduced β-nicotinamide adenine dinucleotide phosphate

P.R.O.D. :

pentoxyresorufin-O-dealkylase

TNFα :

tumor necrosis factor α

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Authors and Affiliations

  1. Laboratoire des protéines, CNRS URA 1188, Université de Paris V, 45 rue des Saints-Pères, F-75270, Paris Cedex 06, France

    M. Sedqi, P. Jollès & D. Migliore-Samour

  2. Laboratoire de chimie et biochimie pharmacologiques et toxicologiques, CNRS URA 400, Université de Paris V, 45 rue des Saints-Pères, F-75270, Paris Cedex 06, France

    M. Delaforge & D. Mansuy

  3. Laboratoire de génétique neurogénétique et comportement, CNRS URA 1294, Université de Paris V, 45 rue des Saints-Pères, F-75270, Paris Cedex 06, France

    B. Martin

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  1. M. Sedqi
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  6. D. Migliore-Samour
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Sedqi, M., Delaforge, M., Mansuy, D. et al. Immunostimulating lipopeptide, LtriP (RP 56142): Comparison of the effect on hepatic cytochrome P 450 modulation and radioprotection in male and female of three mouse strains. Experientia 51, 790–798 (1995). https://doi.org/10.1007/BF01922432

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