AIDSWEEKLY Plus; Monday, December 8, 2003
Staff Medical Writers

"The anti-HIV drug 3'-azido-3'-deoxythymidine (AZT) is the drug of choice for preventing maternal-fetal HIV transmission during pregnancy," scientists in the United States explained.

A.C. Collier and colleagues at the University of Nevada conducted a study "to assess the cytotoxic effects of AZT on human placenta in vitro."

"The mechanisms of AZT-induced effects were investigated using JEG-3 choriocarcinoma cells and primary explant cultures from term and first-trimester human placentas," they wrote in the journal Toxicology and Applied Pharmacology. "Cytotoxicity measures included trypan blue exclusion, MTT, and reactive oxygen species (ROS) assays."

"Apoptosis was measured with an antibody specific to cleaved caspase-3 and by rescue of cells by the general caspase inhibitor Boc-D-FMK," while "the effect of AZT on the activities of glutathione-S-transferase, beta-glucuronidase, UDP-glucuronosyl transferase, cytochrome P450 (CYP) 1A, and CYP reductase (CYPR) in the placenta was assessed using biochemical assays and immunoblotting," according to the report.

"AZT increased ROS levels, decreased cellular proliferation rates, was toxic to mitochondria, and initiated cell death by a caspase-dependent mechanism in the human placenta in vitro," test results revealed. "In the absence of serum, the effects of AZT were amplified in all the models used. AZT also increased the amounts of activity of GST, beta-glucuronidase, and CYP1A, whereas UGT and CYPR were decreased."

These findings show that "AZT causes apoptosis in the placenta and alters metabolizing enzymes in human placental cells," and "have implications for the safe administration of AZT in pregnancy with respect to the maintenance of integrity of the maternal-fetal barrier," the researchers concluded.

Collier and coauthors published their study in Toxicology and Applied Pharmacology (3'-Azido-3'-deoxythymidine (AZT) induces apoptosis and alters metabolic enzyme activity in human placenta. Toxicol Appl Pharmacol. 2003 Oct 15;192(2):164-73.

For more information, contact A.C. Collier, University of Nevada, 1664 N Virginia St., Mail Stop 199, Reno, NV 89557, USA.

Publisher contact information for the journal Toxicology and Applied Pharmacology is: Academic Press Inc., Elsevier Science, 525 B St., Ste. 1900, San Diego, CA 92101-4495, USA.

The information in this article comes under the major subject areas of Adverse Drug Effects, AIDS & HIV and Obstetric.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Collier AC, Helliwell RJ, Keelan JA, et al., "3'-azido-3'-deoxythymidine (AZT) induces apoptosis and alters metabolic enzyme activity in human placenta", Toxicol Appl Pharmacol. 2003 Oct 15;192(2):164-73.

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