Cilastatin has been shown to prevent various
drug-induced nephrotoxicities and confer renoprotection in a mouse model of
glycerol-mediated
rhabdomyolysis-induced
acute kidney injury (AKI). The present study aimed to investigate whether
cilastatin attenuates wasp
sting-induced AKI in rats. Male Wistar rats were divided into the control,
cilastatin, AKI, and AKI + cilastatin groups. Nephrotoxicity was assessed using renal function,
rhabdomyolysis (
creatine kinase, CK) and
intravascular hemolysis (
lactate dehydrogenase, LDH) markers, and histological changes. In addition, tubular injury
biomarkers, apoptosis, oxidative stress markers,
complement C3 expression, and urine and blood
myoglobin levels were examined. Compared with the control or
cilastatin group, the AKI group showed significant histological damage, increased levels of CK, LDH, and
creatinine, and increased
mRNA expression of tubular injury
biomarkers.
Cilastatin ameliorated
wasp venom-induced kidney injury by attenuating oxidative stress and apoptosis.
Cilastatin also reduced C3 expression in the renal tubular cells. In addition,
cilastatin reduced serum
myoglobin levels and increased urine
myoglobin concentrations. Therefore,
megalin blockade with
cilastatin attenuates
wasp venom-induced AKI owing to its antioxidative and antiapoptotic properties.