Influence of anaesthetics on PAF-acether-induced death in mice

PROSTAGLANDINS

Pharmawlogid studiesmditJmanol-inducedtiitis Kemeny, M. Csato and A. Dobozy. Dept. L. University,Szeged,Hungary

of

Dermatology, Albert

Szent-Gysrgyi

Dithrenolis the main therapeuticagent used for the local treatmentof psoriasis.The usefulnessof this compound is however highly limited by its irritativeeffect on the skin. In the present work the effect of differentpharmacologicalsubstancieson dithranol-induced irritativedermatitiswas studied both in mice and humans. Irritativedermatitiswas elicitedby painting the ears of CFLP female mice wiht 20 pm of a 0.5 % w/v solutionof dithranolin aceton : olive oil (4:l).One group of animals has been treated with the PAP-antagonist BN 52021 one hour prior to the elicitationof the Crmatitis in doses of 5-100 mg/kg body weight i.p. Other groups of mice receivedpretreatmentwith the entihistamin clemestineTevegyl@; 4 &kg i.p.), indcmethacin(20 w/kg p.o.) or with the antioxidants,superoxide dismutase (SOD), PeroxinonnR (20 mg/kg i.p.) end MTIQ-DS (2.2 dimethyl-4-methansulphcnic acid sodium-1.2-dihydrochinclin ; 240 mg/kg i.p.).The dermatitiswes characterized by the meesurerwnt_~ the ear thiclmess of the animals 24 hours after the elicitationend is expressed in units of 10 mn. Vehicletreated animals served es control.Dithrenolinduceda consistentand significantincrease in the thicknessof the ears as comparedto the controls (AT = 15.5 + 1.7, p < 0.01).Pretreatmentof the animalswith BN 52021 reducedsignificantly the ear swellingin a dose-dependent manner (AT = 9.8 + 1.4, p < 0.01). The entihisteminclemastine (AT = 6.5 + 1.1, p < O.Ol), the cyclooxygenaseinhibitor indcmethacin(AT = 8.1 + 2.2, p < 0.01) and the antioxidants, SOD (AT = 9.4 + 1.4, p < 0.01) end MTDS-DS (AT = 9.3 + 2.2, p < 0.01) also proved to be effectivein the reductionof the dermatitisin mice. In addition,BN 52021 in a 0.45 % oinment appearedto diminishthe dithracol-induced irritativedermatitis irritative in humans, too. These date provide evidenceof the involvementof PAF in dithranol-induced dermatitisin mice, also support the already presumed roles for histemin,prostaglandinsand reactive BN 52021 might open futureprospectsto cvercome some oxygen radicals.Furthermore,the PAP-antagonist limitationsin the practicaluse of dithranol.

0

INFLUENCE

OF ANAESTHETICS

Criscuoli

M., Department

Via Livornese

ON PAF-ACETHER-INDUCED of Pharmacology,

DEATH IN MICE. Subissi A. and

Laboratori

Guidotti

S.p.A.,

402, 56010 S. Piero a Grade, Piss, Italy

death in mice is proposed as a convenient in viva model for the screening of potential antagonists of this phospholipid autacoid.

PAF-acether-induced

This test may be performed either in conscious or in anaesthetized animals. Since anaesthetics may have profound effects upon responses of various test systems to pharmacological on PAF-x&her-induced Urethane

produced

pentobarbital

stimulation,

lethality a

the effects of different in mice were evaluated.

dose-dependent

and secobarbital

inhibition

produced

of

anaesthetics

PAF-acether

a dose-dependent

toxicity,

potentiation,

while

ketamine was devoid of effects. Both protection by urethane and potentiation by pentobarbital did not appear in adrenalectomized mice. These results suggest that the actions reported above are mediated through an increased (urethane) or decreased (barbiturates) secretion of catecholamines from the adrenal medulla.

This study was supported

834

by Istituto Mobiliare

Italiano.

MAY

1988 VOL.

35 NO. 5