Induction of cytochrome P450 3A1 expression by diallyl disulfide: protective effects against cyclophosphamide-induced embryo-fetal developmental toxicity.
The protective effects of diallyl disulfide (DADS) on cyclophosphamide (CP)-induced developmental toxicity and the possible mechanisms involved in this protection were investigated in rats. In order to study the mechanisms involved in the protection, we examined the effects of DADS on the expression of cytochrome P450 (CYP) 3A1 in the maternal liver and placenta and oxidative stress in the maternal hepatic tissues caused by CP. CP caused severe embryo-fetal developmental toxicity and hepatic oxidative stress. In contrast, DADS treatment significantly attenuated CP-induced developmental toxicity and oxidative damage in the maternal liver. DADS also significantly increased expression of CYP3A1 in the maternal liver and placenta. These results indicate that the protective effects of DADS against CP-induced developmental toxicity may be due to its ability to promote detoxification of CP, primarily by inducing CYP3A1 expression in the maternal liver and placenta, and its potent antioxidant effects.
College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea; Jeonbuk Department of Non-human Primate, Korea Institute of Toxicology, Jeonbuk 580-185, Republic of Korea.
Sung-Hwan
SH
Kim
College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
In-Chul
IC
Lee
College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
Hyung-Seon
HS
Baek
College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
Changjong
C
Moon
College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
Sung-Ho
SH
Kim
College of Pharmacy, Chosun University, Gwangju 501-759, Republic of Korea.
Jin Cheol
JC
Yoo
College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea; Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Republic of Korea. Electronic address: dvmmk79@gmail.com.
In-Sik
IS
Shin
College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea. Electronic address: toxkim@jnu.ac.kr.
Jong-Choon
JC
Kim
D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D003520:Cyclophosphamide / Q000633:toxicity*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D004220:Disulfides / Q000494:pharmacology*; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D008658:Inactivation, Metabolic / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D020011:Protective Agents / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D018675:Toxicity Tests
D000498:Allyl Compounds; D004220:Disulfides; D020011:Protective Agents; C028009:diallyl disulfide; D003520:Cyclophosphamide; C465138:Cyp3a23-3a1 protein, rat; D051544:Cytochrome P-450 CYP3A
Cyclophosphamide; Cytochrome P450 3A1; Developmental toxicity; Diallyl disulfide; Oxidative stress