Protein carbonyl formation in blood plasma by cephalosporins.
Cephalosporin antibiotics caused the formation of carbonyl groups in the plasma proteins both in vivo and in vitro. After the administration of either moxalactam (3 g/day) or cefotaxime (2 g/day) to patients for 7 days, the carbonyl contents in the plasma proteins increased markedly as determined by the 2,4-dinitrophenylhydrazine (DNPH) method. The increase in protein carbonyl groups was also visualized by the conjugation of plasma proteins with fluorescein thiosemicarbazide (FTSC) and subsequent electrophoresis. When blood plasma was incubated with cephalosporins, most of the cephalosporins tested caused the carbonyl formation in plasma proteins to significant degrees in a concentration-dependent manner. Although a number of plasma proteins and other nonplasma proteins could be modified by cephalosporins in vitro, the plasma albumin was most markedly modified in vivo as well as in vitro. The protein carbonyl formation by cephalosporins was inhibited by ascorbic acid, reduced glutathione, and cysteine, but it was not affected by FeSO4, CuSO4, desferrioxamine, EDTA, catalase, superoxide dismutase, uric acid, alpha-tocopherol, and mannitol. Sodium borohydride, when applied to moxalactam-treated plasma proteins, markedly reduced the reactivities of the protein with FTSC or DNPH, indicating that the observed reactivities of the cephalosporin-treated proteins toward FTSC or DNPH are actually due to the protein carbonyl groups. These data suggest that cephalosporins can oxidatively modify proteins in blood plasma and other tissues and that the oxidative modification of proteins may be involved in the adverse reactions observed frequently following cephalosporin therapy.
Jung
Y
Y
Department of Biochemistry, Chonnam University Medical School, Kwangju, Korea.
Chay
K
K
Song
D
D
Yang
S
S
Lee
M
M
Ahn
B
B
D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001798:Blood Proteins / Q000737:chemistry / Q000187:drug effects*; D002439:Cefotaxime / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D008670:Metals / Q000494:pharmacology; D009070:Moxalactam / Q000494:pharmacology; D010084:Oxidation-Reduction
D000975:Antioxidants; D001798:Blood Proteins; D002511:Cephalosporins; D002614:Chelating Agents; D008670:Metals; D005978:Glutathione; D003545:Cysteine; D002439:Cefotaxime; D001205:Ascorbic Acid; D009070:Moxalactam