TY - JOUR
T1 - Trifluoroacetylated adducts in spermatozoa, testes, liver and plasma and CYP2E1 induction in rats after subchronic inhalatory exposure to halothane
AU - Oropeza-Hernández, Luis F.
AU - Quintanilla-Vega, Betzabet
AU - Reyes-Mejía, Raul A.
AU - Serrano, Carmen J.
AU - García-Latorre, Ethel A.
AU - Dekant, Wolfgang
AU - Manno, Maurizio
AU - Albores, Arnulfo
N1 - Funding Information:
This research was supported by the European Community, EC INCO-DC contract No. ERB-IC18-CT98-0341. The authors are grateful to M.J. Solı́s-Heredia, A. Gómez and M.L. López, for technical assistance. Thanks are also given to Dr. A. Darszon (Department of Genetics and Molecular Physiology, IBT-UNAM) for proving the confocal microscopy. LFOH was a recipient of a doctoral scholarship from CONACyT/Mexico.
PY - 2003/9/15
Y1 - 2003/9/15
N2 - The induction of cytochrome P450 (CYP) 2E1 in testes and liver and the presence of trifluoroacetylated (TFA) adducts in spermatozoa, testes, liver and plasma were investigated in rats subchronically exposed by inhalation to halothane (15 ppm/4 h/day/5 days/week/9 weeks). After halothane exposure, p-nitrophenol hydroxylase (p-NPH) activity increased 3.2-fold and CYP2E1 apo-protein content 7-fold in testes, whereas in liver, p-NPH increased 2.3-fold and CYP2E1 apoprotein content 1.4-fold. These results suggest a differential inductive effect of halothane on CYP2E1 in these tissues. Moreover, TFA adducts were present in microsomes of testis and liver and in plasma of halothane-treated rats. The immunoblot analysis of testicular microsomes showed two intense TFA protein bands of 63 and 59 kDa, whereas in liver three intense bands of 100, 76 and 63 kDa were observed. Bands of similar molecular weights to those observed in liver were detected in the plasma of halothane-treated animals. In addition, TFA adducts were detected by immunofluorescence in spermatozoa, probably in the acrosome and/or perinuclear theca region, and in the distal tail of spermatozoa. The increase in CYP2E1 apoprotein and p-NPH activity observed in testis and liver microsomes suggests that halothane induces its own biotransformation both hepatically and extrahepatically and in addition, that the nature of the TFA adducts will depend on the proteins present in each tissue. Also, the presence of TFA adducts in spermatozoa may result from the activation of halothane in the reproductive tract. The detailed mechanism of TFA adduct formation and its consequences on the spermatozoa function remain to be fully clarified.
AB - The induction of cytochrome P450 (CYP) 2E1 in testes and liver and the presence of trifluoroacetylated (TFA) adducts in spermatozoa, testes, liver and plasma were investigated in rats subchronically exposed by inhalation to halothane (15 ppm/4 h/day/5 days/week/9 weeks). After halothane exposure, p-nitrophenol hydroxylase (p-NPH) activity increased 3.2-fold and CYP2E1 apo-protein content 7-fold in testes, whereas in liver, p-NPH increased 2.3-fold and CYP2E1 apoprotein content 1.4-fold. These results suggest a differential inductive effect of halothane on CYP2E1 in these tissues. Moreover, TFA adducts were present in microsomes of testis and liver and in plasma of halothane-treated rats. The immunoblot analysis of testicular microsomes showed two intense TFA protein bands of 63 and 59 kDa, whereas in liver three intense bands of 100, 76 and 63 kDa were observed. Bands of similar molecular weights to those observed in liver were detected in the plasma of halothane-treated animals. In addition, TFA adducts were detected by immunofluorescence in spermatozoa, probably in the acrosome and/or perinuclear theca region, and in the distal tail of spermatozoa. The increase in CYP2E1 apoprotein and p-NPH activity observed in testis and liver microsomes suggests that halothane induces its own biotransformation both hepatically and extrahepatically and in addition, that the nature of the TFA adducts will depend on the proteins present in each tissue. Also, the presence of TFA adducts in spermatozoa may result from the activation of halothane in the reproductive tract. The detailed mechanism of TFA adduct formation and its consequences on the spermatozoa function remain to be fully clarified.
KW - CYP2E1
KW - Halothane
KW - Spermatozoa
KW - TFA adducts
UR - http://www.scopus.com/inward/record.url?scp=0042159912&partnerID=8YFLogxK
U2 - 10.1016/S0378-4274(02)00335-1
DO - 10.1016/S0378-4274(02)00335-1
M3 - Artículo
C2 - 12919728
AN - SCOPUS:0042159912
SN - 0378-4274
VL - 144
SP - 105
EP - 116
JO - Toxicology Letters
JF - Toxicology Letters
IS - 1
ER -