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In utero exposure to HAART induces oxidative stress in adult mice offsprings
Author(s) -
Lee Yun Kyung,
Nerurkar Vivek,
Frank Jennifer E,
Nerurkar Pratibha
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1033.3
Subject(s) - offspring , oxidative stress , pregnancy , in utero , endocrinology , medicine , toxicity , insulin resistance , gestation , physiology , weaning , diabetes mellitus , fetus , biology , genetics
Use of nucleoside analogue reverse transcriptase inhibitors (NRTI) during pregnancy reduces HIV infection among newborns and prevents vertical transmission of the virus. The fact that alterations in fetal environment can have long‐term consequences on metabolic and endocrine pathophysiology in adult life raises concern about long‐term safety of uterine exposure to NRTI. Since NRTI can induce mitochondrial toxicity and oxidative stress, we hypothesize that infants exposed to NRTI in utero may be at increased risk of oxidative stress‐associated diseases in adult life. To test our hypothesis, pregnant mice were treated with the NRTI, combivir, two weeks before mating, during mating, pregnancy, delivery and lactation. After weaning the pups also received combivir for two additional weeks. The untreated control mothers received the vehicle, apple juice. Our data indicates that 3 months after birth, the adult offsprings of NRTI‐treated mice had significantly higher levels of blood glucose, total cholesterol and calculated LDL‐cholesterol and reduced levels of hepatic and plasma glutathione, as compared to age‐matched offsprings born to control mothers (p<0.05). Since oxidative stress is implicated in pathophysiology of insulin resistance and diabetes, studies are being conducted to address the effects of oxidative stress on glucose metabolism and mitochondrial toxicity in adult offspring. [Supported by grants in part by the Clinical Research Center of Hawaii (P20 RR011091) and the U.S. Public Health Service grants from the RCMI Program (G12 RR003061)].