Membrane dipeptidase is a glycoprotein involved in the hydrolysis of dipeptides and dehydropeptides. Cilastatin is a reversible, competitive inhibitor of dehydropeptidase I, a renal dipeptidase, with an IC50 value of 0.1μM. It also inhibits bacterial metallo-β-lactamase enzyme CphA with an IC50 value of 178 ± 11μM[4]. Cilastatin at 3 and 6 mg/mL significantly reduced the detachment of renal proximal tubular epithelial cells (RPTECs). Treatment with cilastatin also significantly ameliorated vancomycin-induced nuclear apoptosis of RPTECs[5]. Cilastatin in combination with imipenem protected female CD-1 mice from S. aureus, E. coli, and P. aeruginosa infection[6].
Cilastatin/西司他丁 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Renal primary proximal tubule cells (RPTCs)
100 μM
24 h
To evaluate the protective effect of Cilastatin against diclofenac-induced cytotoxicity. Results showed that Cilastatin reduced the cytotoxicity of diclofenac acyl glucuronide (DLF-AG) by inhibiting OAT1/3-mediated intracellular accumulation.
Br J Pharmacol. 2020 May;177(9):1933-1948.
HEK293 cells
100 μM
24 h
To evaluate the protective effect of Cilastatin against diclofenac-induced cytotoxicity. Results showed that Cilastatin reduced the cytotoxicity of diclofenac acyl glucuronide (DLF-AG) by inhibiting OAT1/3-mediated intracellular accumulation.
To evaluate the protective effect of Cilastatin against gentamicin-induced apoptosis. Results showed that Cilastatin reduced cell detachment, preserved cell morphology, and decreased caspase-3 activation and DNA fragmentation.
Antioxidants (Basel). 2020 Sep 3;9(9):821
rabbit primary proximal tubule cells (rPTCs)
100 µM
10 min
To investigate the inhibitory effect of Cilastatin on Imipenem uptake in rPTCs, results showed that Cilastatin inhibited raOATs-mediated transport of Imipenem.
Acta Pharm Sin B. 2019 Sep;9(5):986-996
hOAT3-HEK293 cells
100 µM
10 min
To investigate the inhibitory effect of Cilastatin on Imipenem uptake in hOAT3-HEK293 cells, results showed that Cilastatin inhibited hOAT3-mediated transport of Imipenem.
Acta Pharm Sin B. 2019 Sep;9(5):986-996
hOAT1-HEK293 cells
100 µM
10 min
To investigate the inhibitory effect of Cilastatin on Imipenem uptake in hOAT1-HEK293 cells, results showed that Cilastatin inhibited hOAT1-mediated transport of Imipenem.
Acta Pharm Sin B. 2019 Sep;9(5):986-996
Cilastatin/西司他丁 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Kunming mice
Diclofenac-induced acute kidney injury model
Intraperitoneal injection
25, 50, 100 mg/kg
Single dose
To evaluate the protective effect of Cilastatin against diclofenac-induced acute kidney injury. Results showed that Cilastatin alleviated diclofenac-induced acute kidney injury by restoring the redox balance, suppressing inflammation, and reducing apoptosis.
Br J Pharmacol. 2020 May;177(9):1933-1948.
Wistar rats
Gentamicin-induced acute kidney injury model
Intraperitoneal injection
150 mg/kg
Once daily for 8 days
To evaluate the protective effect of Cilastatin against gentamicin-induced renal injury. Results showed that Cilastatin reduced serum creatinine, BUN, KIM-1 levels, improved renal morphology, and decreased oxidative stress and inflammatory responses.
Antioxidants (Basel). 2020 Sep 3;9(9):821
Female Wistar rats
Cisplatin-induced nephrotoxicity model
Intraperitoneal injection
150 mg/kg
Once daily for 5 days
Cilastatin significantly alleviated cisplatin-induced nephrotoxicity, including weight loss, renal dysfunction (elevated serum creatinine and BUN), and renal tissue damage. Additionally, Cilastatin reduced cisplatin-induced apoptosis and lipid peroxidation and restored alterations in renal lipid distribution.
J Lipid Res. 2018 Sep;59(9):1561-1574
New Zealand white rabbits
Imipenem-induced acute kidney injury model
Intravenous injection
200 mg/kg
Single dose, observed for 48 hours
To investigate the protective effect of Cilastatin on imipenem-induced kidney injury, results showed that Cilastatin alleviated imipenem-induced kidney injury.
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