Paper Information

Title: 

EMBRYOTOXICITY OF ACETAMINOPHEN IN BALB/C MOUSE

Type: SPEECH
Author(s): JALALI M.,NIKRAVESH M.R.
 
 
 
Name of Seminar: IRANIAN CONGRESS OF TOXICOLOGY
Type of Seminar:  CONGRESS
Sponsor:  SOCIETY OF TOXICOLOGY
Date:  2004Volume 8
 
 
Abstract: 

IN THE PAST FEW DECADES IT HAS BECOME INCREASINGLY EVIDENT THAT HUMAN EMBRYOS ARE SUBJECT TO A VARIETY OF ENVIRONMENTAL INFLUENCES THAT MIGHT HAVE DELETERIOUS EFFECTS ON THEIR DEVELOPMENT. ONE AGENT TO WHICH MANY HUMAN MOTHERS MAY BE EXPOSED IS ACETAMINOPHEN. ACETAMINOPHEN IS A WIDELY USED ANALGESIC AND ANTI-PYRETIC WHICH IS CONSIDERED SAFE AT THERAPEUTIC LEVELS DURING PREGNANCY. THE AIM OF THE STUDY WAS TO EVALUATE THE TOXIC EFFECT OF ACETAMINOPHEN ON MOUSE FETUSES.
IN THIS INVESTIGATION, WE ADMINISTERED THERAPEUTIC DOSE OF ACETAMINOPHEN (48.5MG/KG) TO BALB/C MICE DURING CRITICAL PERIODS OF PREGNANCY (DAY'S 8-11 GESTATION). WE ALSO ADMINISTRATED THE DOUBLE THERAPEUTIC DOSE (97MG/KG) OF ACETAMINOPHEN TO OTHER EXPERIMENTAL GROUP. THE CONTROLS WERE RECEIVED THE SAME VOLUME OF PHISILOGICAL SERUM. FROM DAY 14 OF GESTATION SOME OF THE MICE IN BOTH EXPERIMENTAL AND CONTROL GROUP WERE SACRIFICED AND THEIR EMBRYOS WERE COLLECTED FOR FIXATION, PROCESSED, SERIALLY SECTIONED AND STAINED FOR HISTOLOGICAL STUDIES. OUR FINDING SHOWED THAT ADMINISTRATION OF THERAPEUTIC DOSES OF ACETAMINOPHEN RESULTED IN SEVERE DEFECT IN DEVELOPING LIVER. THESE DEFECTS WERE CONSIST OF DELAY IN FORMATION LOBULES, REMAINING OF HEMOPOITIC CENTRE UP TO LAST DAY OF FETAL PERIOD, INCREASIG THE NUMBER OF MEGACARYOCITES AS WELL AS OTHER DEFECTS SUCH AS VISUAL SYSTEM, INTRAUTERINE GROSS RETARDATION AND FETAL RESORPTION AMONG OTHER DEVELOPMENTALLY RELATED MALFORMATIONS ARE THOSE AFFECTING THE CENTRAL NERVOUS SYSTEM, URINARY TRACT AND SKELETAL SYSTEM. ALTHOUGH ADMINISTRATION OF A DOUBLED THERAPEUTIC DOSE CAUSED A FURTHER INCREASE IN THE SEVERITY AND FREQUENCY OF THE MALFORMATIONS, THERE WAS NO SIGNIFICANT DIFFERENCE BETWEEN EXPERIMENTAL GROUPS
.
IT SEEMS THAT WHEN PREGNANT ANIMALS WERE EXPOSED TO ACETAMINOPHEN, IT IS METABOLIZED IN THE LIVER AND CONVERTED INTO POTENTIALLY TOXIC METABOLITES. THESE METABOLITES CAN PASS THROUGH THE PLACENTA AND MAY CAUSE MALFORMATION IN THE EMBRYO, THE MECHANISM BY WHICH ACETAMINOPHEN AFFECTS COMPONENTS OF THE DEVELOPING EMBRYO REMAINS TO BE DETERMINED
.

 
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