Nephron Transport and Renal Tubular Effects of Cephaloridine in Animals

Child, Korean J; Dodds, Michael

doi:10.1111/j.1476-5381.1967.tb02142.x

Cited by 44 publications

(11 citation statements)

References 19 publications

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“…Therefore, many attempts have been made to prevent nephrotoxicity by administering protective agents (2,3,5,7,9,14,25,26,28). For example, probenecid (7,25,28), p-aminohippurate (26), and other organic anions (7) have been found to reduce the nephrotoxicity of cephaloridine in experimental animals.…”

mentioning

confidence: 99%

Protective effect of piperacillin against nephrotoxicity of cephaloridine and gentamicin in animals

Hayashi

Watanabe

Kumano

et al. 1988

Antimicrob Agents Chemother

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The protective effect of piperacillin against the nephrotoxicity of cephaloridine and gentamicin was examined in experimental animals. In rabbits, piperacillin was infused at a dose of 1 mg/kg (body weight) per min over 225 min and cephaloridine (300 mg/kg) was intravenously administered as a bolus 45 min after the start of a drip infusion. Blood urea nitrogen, serum creatinine, and N-acetyl-jo-D-glucosaminidase (NAG) in urine were measured as the renal toxicological parameters before and 24 h after cephaloridine dosing. Although the single administration of cephaloridine significantly elevated these parameters, the elevation was prevented by the concomitant administration of piperacillin. The protective effect of piperacillin was superior to those of cephalothin and fosfomycin. In rats, piperacillin (1,000 mg/kg) was intravenously administered and immediately followed by the intramuscular administration of gentamicin (100 mg/kg) every 24 h for 5 days. When piperacillin was concomitantly administered with gentamicin, the elevations of blood urea nitrogen, serum creatinine, and urinary NAG were significantly lower than when gentamicin was given alone. The concomitant administration of piperacillin resulted in a significant protective effect against the nephrotoxicity of cephaloridine in rabbits and of gentamicin in rats. Histopathological observation also supported the protective effect of piperacillin. The protective mechanism of piperacillin might be the inhibition of transport from the peritubular side to tubular cells for cephaloridine and from both the peritubular and luminal sides for gentamicin.Large doses of cephaloridine cause acute renal cell lesions of the proximal tubules in experimental animals (1,4,6,24,29). Gentamicin shows both nephrotoxicity and ototoxicity in a variety of experimental animals (10,11,15,17,18,(20)(21)(22)(23) and humans (16,31). Therefore, many attempts have been made to prevent nephrotoxicity by administering protective agents (2,3,5,7,9,14,25,26,28). For example, probenecid (7, 25, 28), p-aminohippurate (26), and other organic anions (7) have been found to reduce the nephrotoxicity of cephaloridine in experimental animals.Previously, we reported the pharmacokinetic changes of cefazolin and cefoperazone in combination with piperacillin in rabbits (13). Urinary excretion of cefazolin and cefoperazone was reduced, and subsequently, drug half-lives in serum were prolonged by the concomitant administration of piperacillin. However, the urinary excretion of piperacillin was not affected by the concomitant administration of cefazolin or cefoperazone. From the fact that these threelactams were mainly excreted by tubular secretion, piperacillin seemed to have a higher affinity for the tubular secretion system in rabbits. It is therefore expected that the higher affinity of piperacillin to the tubular secretion system would protect against the nephrotoxicity due to cephaloridine and gentamicin.In this paper, we report the protective effect of piperacillin against the nephrotoxicity of c...

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confidence: 99%

Protective effect of piperacillin against nephrotoxicity of cephaloridine and gentamicin in animals

Hayashi

Watanabe

Kumano

et al. 1988

Antimicrob Agents Chemother

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“…In fact, it is known that CER-induced renal failure can also be prevented by probenecid and other organic anions (2,3,8). Both the renal cortical transport and the toxicity are prevented by the inhibitors of organic acid secretion, sug gesting that the nephrotoxicity of CER is related to the high intracellular concentration that results from its ac tive transport.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, these oxygen radicals might have induced the peroxidation of the cellular membrane at the glomerulus, resulting in the functional damage of the glomerulus (25). It has been reported that the LD50 value of CER by sin gle intravenous administration in rats was 1.2 to 1.4 g/kg body weight and that the ND50 (nephrotoxic dose) value was 1.0 g/kg body weight (2,4). The dose of CER used in the present study was lower as compared with that in the previous reports that referred to the CER-induced ARF.…”

Section: Discussionmentioning

confidence: 99%

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Effects of KW-3902, a Novel Adenosine A1-Receptor Antagonist, on Cephaloridine-Induced Acute Renal Failure in Rats

Nagashima

Kusaka

Satô

et al. 1994

Japanese Journal of Pharmacology

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ABSTRACT-We investigated the possible renal protective effects of -1,3 dipropylxanthine), a selective and potent adenosine A,-receptor antagonist, against cephaloridine (CER) induced acute renal failure (ARF) in rats. ARF was induced by intravenous injection of CER at a dose of 600 mg/kg body weight. KW-3902 at doses higher than 0.01 mg/kg (p.o.) dose-dependently attenuated the decrease of creatinine clearance and the increase of proteinuria in rats with CER-induced ARF. In contrast, furosemide and trichlormethiazide (TCM) increased urinary protein and aggravated the serum parameters. These results suggest that KW-3902 has some advantages over furosemide and TCM when used in combi nation with CER. In the diuretic study in the rats with established ARF induced by CER, KW-3902, furosemide and TCM caused a significant increase in sodium excretion, whereas acetazolamide was ineffec tive. These results suggest that the proximal tubule is functionally damaged in rats with CER-induced ARF, in accord with the histological observation demonstrating the degeneration of the proximal tubule. From the fact that KW-3902 induces diuretic action even in CER-induced ARF, it is suggested that KW-3902 acts, directly or indirectly, on the proximal tubule or other tubular sites in the kidney, resulting in the diuretic effect.

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“…Both tubular transport and nephrotoxic ity of CER were prevented in the presence of competitive inhibitors for organic acid transport, e.g., probenecid, PAH, and benzyl penicillin (5,(12)(13)(14)(15); and it has been concluded that CER nephrotoxicity is related to the high intracellular concentration resulting from its active trans port (14)(15)(16)(17)(18). It also has been recently reported that co administration of a large volume of physiological saline reduced CER-nephrotoxicity (9).…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of N-Acyl Amino Acids (NAAs) on Cephaloridine (CER) Nephrotoxicity in Rabbits

Hirouchi

Naganuma

Kawahara

et al. 1993

Japanese Journal of Pharmacology

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Nephron Transport and Renal Tubular Effects of Cephaloridine in Animals

Cited by 44 publications

References 19 publications

Protective effect of piperacillin against nephrotoxicity of cephaloridine and gentamicin in animals

Protective effect of piperacillin against nephrotoxicity of cephaloridine and gentamicin in animals

Effects of KW-3902, a Novel Adenosine A1-Receptor Antagonist, on Cephaloridine-Induced Acute Renal Failure in Rats

Protective Effect of N-Acyl Amino Acids (NAAs) on Cephaloridine (CER) Nephrotoxicity in Rabbits

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