Reduction of experimental gentamicin nephrotoxicity in rats by dietary calcium loading

Bennett, William M.; Elliott, William C.; Houghton, Donald C.; Gilbert, David N.; DeFehr, J. M.; McCarron, David A.

doi:10.1128/aac.22.3.508

Cited by 71 publications

(39 citation statements)

References 16 publications

(11 reference statements)

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“…These reports demonstrate the ability of divalent cations to prevent and reverse aminoglycoside-induced neurotoxicity and ototoxicity acutely in vitro. In a similar fashion, recent reports (1,34) have demonstrated that oral calcium loading protects against gentamicin-induced acute renal excretory failure. The present experiments were undertaken to better characterize the effect of dietary calcium supplementation to ameliorate aminoglycoside-induced nephrotoxicity.…”

Section: Discussionmentioning

confidence: 64%

“…oral calcium loading on gentamicin-induced renal excretory failure recently reported by Bennett and co-workers (1,34).…”

Section: Discussionmentioning

confidence: 99%

“…Since increases in mitochondrial calcium content may be detrimental to mitochondrial function (8), the use of methods that attempt to limit calcium uptake during the mitochondrial isolation procedure is critical in obtaining a mitochondria preparation in vitro reflective of mitochondrial function in situ. In this regard, a homogenizing solution containing both 1 supplemented group than in the standard diet group. And after § P < 0.01 (group 2 relative to group 1).…”

Section: Mitochondrial Isolationmentioning

confidence: 99%

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Calcium is a competitive inhibitor of gentamicin-renal membrane binding interactions and dietary calcium supplementation protects against gentamicin nephrotoxicity.

Humes¹,

Sastrasinh²,

Weinberg³

1984

J. Clin. Invest.

126

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Section: Discussionmentioning

confidence: 64%

“…oral calcium loading on gentamicin-induced renal excretory failure recently reported by Bennett and co-workers (1,34).…”

Section: Discussionmentioning

confidence: 99%

Section: Mitochondrial Isolationmentioning

confidence: 99%

See 1 more Smart Citation

Calcium is a competitive inhibitor of gentamicin-renal membrane binding interactions and dietary calcium supplementation protects against gentamicin nephrotoxicity.

Humes¹,

Sastrasinh²,

Weinberg³

1984

J. Clin. Invest.

126

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“…In one of these studies, Antoine et al 19 have experimentally shown that statins reduce tubular uptake of AG. In another study, Bennett et al 20 demonstrated that increased dietary calcium load reduces tubular uptake of gentamicin.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Grape Seed Proanthocyanidin Extract in Preventing Amikacin-Induced Nephropathy

et al. 2012

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Background/Aims: Nephrotoxicity induced by aminoglycosides (AGs) limits their clinical use. As yet, no molecules have been approved to prevent AG nephropathy. We aim to investigate the effectiveness of grape seed proanthocyanidin extract (GSPE) in the prevention of amikacin (AK)-induced nephrotoxicity. Methods: A total of 24 rats were allocated into control, GSPE, AK, and AK + GSPE groups. While 1 mL saline was administered for 6 days in control and AK groups, 100 mg/kg GSPE was administered in GSPE and AK + GSPE groups. On day 7, intraperitoneal (i.p.) saline was administered in control and GSPE groups, while 1.2 g/kg i.p. AK was administered in AK and AK + GSPE groups. The experiment was terminated on day 9. Blood samples were taken for the measurement of renal functions. Renal tissues of the rats were removed for the analysis of malondialdehyde (MDA), total oxidant system (TOS), total antioxidant system, oxidative stress index (OSI), and for histopathological examination. Results: MDA level was found to be lower in GSPE group compared with other study groups. There was significantly more renal histopathological damage and higher blood urea nitrogen, creatinine, TOS, OSI, and MDA levels in the AK group compared with the control and AK + GSPE groups. The same parameters showed significant improvement in AK + GSPE group compared with AK group. Conclusion: Our findings demonstrate for the first time that GSPE reduces oxidative damage in AK nephropathy and provides biochemical and renal histopathological improvements.

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“…10,24,25) Data from our laboratory has also shown that latamoxef and ceftriaxone protect against gentamicin-induced nephrotoxicity. 26) Aminoglycosides are frequently used in combination with fleroxacin or other broad-spectrum cephalosporins to treat patients with major infections.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Fleroxacin against the Nephrotoxicity of Isepamicin in Rats

Yazaki¹,

Yoshiyama²,

Wong³

et al. 2002

Biological & Pharmaceutical Bulletin

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Its advantages included having low nephrotoxicity and effectiveness with only once daily dosing in the treatment of numerous infections.2,3) Since fleroxacin is often combined with isepamicin, and this combination has been shown to be very effective as a first-line antibiotic combination in the treatment of severe infections, the potential of additive nephrotoxicity in the fleroxacin isepamicin combination regimen is of great clinical importance.Different compounds or drugs used concomitantly with aminoglycosides may either increase or decrease aminoglycoside toxicity. In fact, drugs such as cisplatinum 4) and vancomycin 5) increase the nephrotoxicity of aminoglycosides, while recent studies showed that poly-L-aspartic acid, 6) daptomycin, 7,8) carbenicillin, 9) ticarcillin 10) and ceftriaxone 11) protected the kidney against aminoglycoside-induced nephrotoxicity.Fleroxacin is a synthetic broad-spectrum antibiotic belonging to the class of fluoroquinolones.12) It shows good antibacterial activity against many gram-negative bacteria, and less activity against gram-positive bacteria. 13,14) A recent investigation showed that fleroxacin (intraperitoneally) protected against gentamicin-induced nephrotoxicity in rats when both drugs were administered in combination. 15) In Japan, fleroxacin is given orally. In rats, fleroxacin reaches peak serum levels within 1 h after oral administration, with a half-life of 2.3 h. 16) In contrast with several other quinolones, fleroxacin is not metabolized and is mainly excreted unchanged in the urine.14,17,18) Fleroxacin reaches peak kidney concentrations within 0.5-1 h. In fact, high concentrations of fleroxacin have been measured in the kidney of rabbits 19) and in the human kidneys. 20) Moreover, the accumulation of fleroxacin was higher in the kidneys of patients with symptomatic complicated urinary tract infections. 21)To our knowledge, there are no data on the effects of fleroxacin (orally) on the nephrotoxicity of administered isepamicin. In view of the particular distribution of fleroxacin within the kidney, we have evaluated the nephrotoxic potential of the fleroxacin (orally) isepamicin combination regimen. MATERIALS AND METHODSAdult male Wistar rats weighing between 130-150 g were used. The animals were housed in a light-controlled room (lights on from 0800 to 2000 h) at a room temperature of 24Ϯ1°C and humidity of 60Ϯ10% for 1 week. They were acclimated for one week, and they had free access to food and water throughout the experiment.Isepamicin was dissolved in saline (0.9% NaCl). Fleroxacin was suspended in 0.3% sodium carboxymethyl cellulose (CMC-Na).For 14 d, animals were given one of the 4 regimens: a single injection of either saline (intraperitoneally) and CMC-Na (orally), saline (intraperitoneally) and fleroxacin 100 mg/kg (orally), isepamicin 300 mg/kg (intraperitoneally) and CMCNa (orally) or isepamicin (intraperitoneally) with fleroxacin (orally) at the same dose as when used alone. Animals were injected at 1300 h. This dosing schedule was determined from ...

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Reduction of experimental gentamicin nephrotoxicity in rats by dietary calcium loading

Cited by 71 publications

References 16 publications

Calcium is a competitive inhibitor of gentamicin-renal membrane binding interactions and dietary calcium supplementation protects against gentamicin nephrotoxicity.

Calcium is a competitive inhibitor of gentamicin-renal membrane binding interactions and dietary calcium supplementation protects against gentamicin nephrotoxicity.

The Effect of Grape Seed Proanthocyanidin Extract in Preventing Amikacin-Induced Nephropathy

Protective Effect of Fleroxacin against the Nephrotoxicity of Isepamicin in Rats

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