Nephrotoxic potential of first-, second-, and third-generation cephalosporins

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Abstract
First-, second-, and third-generation cephalosporins were investigated for their peroxidative and nephrotoxic potential. Renal cortical slices from male Wistar rats were incubated at 37° C for 1 h in a phosphate-buffered medium containing the cephalosporin (1.25, 2.5, 5 or 10 mg/ml). In another series of experiments 5 mg/ml cephalosporin was incubated under the same conditions for 30, 60, 90 and 120 min. Subsequently, slices were incubated for 60 or 90 min in a bicarbonate- or phosphate-buffered medium containing pyruvate or tetraethylammonium (TEA) to determine gluconeogenesis and TEA accumulation, respectively. The peroxidative potential was determined at the end of the first incubation by measuring the increase in the malondialdehyde (MDA) content in renal cortical slices. The nephrotoxic potential was determined at the end of the second incubation by measuring the decrease in accumulation of the organic ion (TEA) and decrease of pyruvate-stimulated gluconeogenesis in renal cortical slices. First-generation cephalosporins, cephaloridine and cephalothin showed a time- and concentration-dependent increase in MDA content and a decrease in TEA accumulation and gluconeogenesis by renal cortical slices. Cefazolin, another first generation cephalosporin, showed a weak peroxidative and practically no nephrotoxic potential. In the group of second-generation cephalosporins, cefotiam showed a weak peroxidative potential comparable to that of cefoxitin but had a much greater nephrotoxic potential which was similar to that of cephaloridine. The third-generation cephalosporins, cefotaxime and cefoperazone showed a low peroxidative and no nephrotoxic potential. Based on their nephrotoxic potential, the cephalosporins investigated in the present study could be ranked as follows: cephaloridine > cefotiam > cephalothin > cefoxitin > cefazolin > cefoperazone ≧ cefotaxime.