2019
DOI: 10.1016/j.apsb.2019.02.005
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Cilastatin protects against imipenem-induced nephrotoxicity via inhibition of renal organic anion transporters (OATs)

Abstract: Imipenem is a carbapenem antibiotic. However, Imipenem could not be marketed owing to its instability and nephrotoxicity until cilastatin, an inhibitor of renal dehydropeptidase-I (DHP-I), was developed. In present study, the potential roles of renal organic anion transporters (OATs) in alleviating the nephrotoxicity of imipenem by cilastatin were investigated in vitro and in rabbits. Our results indicated that imipenem and cilastatin were substrates of hOAT1 and hOAT3. Cilastatin inhibited hOAT1/3-mediated tr… Show more

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Cited by 27 publications
(31 citation statements)
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“…Indeed, reducing the renal accumulation of toxic substances is an important mechanism underlying the protective effect of cilastatin. It was reported that cilastatin inhibited the transport of vancomycin, cyclosporin A, cisplatin and imipenem into the kidney and thereby limited the nephrotoxicity of these drugs (Camano et al, ; Huo et al, ; Perez et al, ). Our results also found that cilastatin reduced the renal distribution of diclofenac and diclofenac acyl glucuronide (Figures b and d).…”
Section: Discussionmentioning
confidence: 99%
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“…Indeed, reducing the renal accumulation of toxic substances is an important mechanism underlying the protective effect of cilastatin. It was reported that cilastatin inhibited the transport of vancomycin, cyclosporin A, cisplatin and imipenem into the kidney and thereby limited the nephrotoxicity of these drugs (Camano et al, ; Huo et al, ; Perez et al, ). Our results also found that cilastatin reduced the renal distribution of diclofenac and diclofenac acyl glucuronide (Figures b and d).…”
Section: Discussionmentioning
confidence: 99%
“…Mock‐, hOAT1‐, and hOAT3‐HEK293 cells were routinely maintained in DMEM (Invitrogen, USA) supplemented with 10% FBS (heat inactivated), 1% non‐essential amino acid solution, 100 U·ml −1 penicillin and 0.1 mg·ml −1 streptomycin and G418 sulfate (400 μg·ml −1 ). Renal primary proximal tubule cells were isolated from mice according to a previous method with modifications (Huo et al, ; Li et al, ). Briefly, mice were killed and the kidneys were removed and minced in a sterile cell culture dish on ice.…”
Section: Methodsmentioning
confidence: 99%
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