RENAL TUBULAR TRANSPORT AND NEPHROTOXICITY OF BETA-LACTAM ANTIBIOTICS - STRUCTURE-ACTIVITY-RELATIONSHIPS

被引:0
作者
TUNE, BM
机构
关键词
BETA LACTAM; CEPHALOSPORIN; MITOCHONDRION; NEPHROTOXIC; TRANSPORT;
D O I
暂无
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Several of the cephalosporin and carbapenem antibiotics produce acute renal failure when given in large single doses. Antibiotic concentrations in the tubular cell, determined by the net effects of contraluminal secretory transport and subsequent movement across the luminal membrane, make the proximal tubule the sole target of injury, and are important determinants of the nephrotoxic potentials of different beta-lactams in different animal species. At least three molecular mechanisms of injury have been shown with cephaloridine, the most widely studied nephrotoxic beta-lactam: (1) lipid peroxidation, (2) competitive inhibition of mitochondrial carnitine (zwitterionic) transport and fatty acid oxidation, and (3) acylation and inactivation of tubular cell proteins, most thoroughly evaluated with mitochondrial anionic substrate transporters. The first two of these injuries are dependent upon one or both of cephaloridine's side group substituents, which are not present on the other nephrotoxic cephalosporins or carbapenems. It is not surprising, therefore, that only toxicity to mitochondrial anionic substrate carriers has been found in studies of the other beta-lactams. However, the several effects of cephaloridine on the tubular cell indicate a potential for different mechanisms of attack on different molecular targets. Continuing studies of the effects of existing and newly developed beta-lactams are likely to identify further nephrotoxic mechanisms of this complex and rapidly growing group of antimicrobials.
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页码:221 / 231
页数:11
相关论文
共 88 条
[41]   CEPHALORIDINE NEPHROTOXICITY - STRAIN AND SEX-DIFFERENCES IN MICE [J].
PASINO, DA ;
MIURA, K ;
GOLDSTEIN, RS ;
HOOK, JB .
FUNDAMENTAL AND APPLIED TOXICOLOGY, 1985, 5 (06) :1153-1160
[42]  
PERKINS RL, 1968, J LAB CLIN MED, V71, P75
[43]   CEPHALORIDINE-INDUCED BIOCHEMICAL-CHANGES AND CYTOTOXICITY IN SUSPENSIONS OF RABBIT ISOLATED PROXIMAL TUBULES [J].
RUSH, GF ;
PONSLER, GD .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1991, 109 (02) :314-326
[44]   CEPHALORIDINE-INDUCED RENAL PATHOLOGICAL AND BIOCHEMICAL-CHANGES IN FEMALE RABBITS AND ISOLATED PROXIMAL TUBULES IN SUSPENSION [J].
RUSH, GF ;
HEIM, RA ;
PONSLER, GD ;
ENGELHARDT, J .
TOXICOLOGIC PATHOLOGY, 1992, 20 (02) :155-168
[45]  
SILVERBLATT F, 1982, REV INFECT DIS, V4, pS360
[46]   NEPHROTOXICITY DUE TO CEPHALORIDINE - A LIGHT- AND ELECTRON-MICROSCOPIC STUDY IN RABBITS [J].
SILVERBLATT, F ;
TURCK, M ;
BULGER, R .
JOURNAL OF INFECTIOUS DISEASES, 1970, 122 (1-2) :33-+
[47]  
STRYER L, 1988, BIOCHEMISTRY-US, P373
[48]   MECHANISM OF ACTION OF PENICILLINS - A PROPOSAL BASED ON THEIR STRUCTURAL SIMILARITY TO ACYL-D-ALANYL-D-ALANINE [J].
TIPPER, DJ ;
STROMINGER, JL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1965, 54 (04) :1133-+
[49]   SAFETY EVALUATION OF MEROPENEM IN ANIMALS - STUDIES ON THE KIDNEY [J].
TOPHAM, JC ;
MURGATROYD, LB ;
JONES, DV ;
GOONETILLEKE, URP ;
WRIGHT, J .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1989, 24 :287-306
[50]  
TRUMP BF, 1968, LAB INVEST, V18, P731