Antiapoptotic Effect of Paricalcitol in Gentamicin-induced Kidney Injury.
While the anti-apoptotic effect of paricalcitol has been demonstrated in various animal models, it is not yet clear whether paricalcitol attenuates the apoptosis in gentamicin (GM)-induced kidney injury. We investigated the effect of paricalcitol on apoptotic pathways in rat kidneys damaged by GM. Rats were randomly divided into three groups: 1) Control group (n=8), where only vehicle was delivered, 2) GM group (n=10), where rats were treated with GM (150 mg/kg/day) for 7 days, 3) PARI group (n=10), where rats were co-treated with paricalcitol (0.2 µg/kg/day) and GM for 7 days. Paricalcitol attenuated renal dysfunction by GM administration in biochemical profiles. In terminal deoxynucleotidyl transferase dUTP nick end labeling staining, increased apoptosis was observed in GM group, which was reversed by paricalcitol co-treatment. Immunoblotting using protein samples from rat cortex/outer stripe of outer medulla showed increased Bax/Bcl-2 ratio and cleaved form of caspase-3 in GM group, both of which were reversed by paricalcitol. The phosphorylated Jun-N-terminal kinase (JNK) expression was increase in GM, which was counteracted by paricalcitol. The protein expression of p-Akt and nitro-tyrosine was also enhanced in GM-treated rats compared with control rats, which was reversed by paricalcitol co-treatment. Paricalcitol protects GM-induced renal injury by antiapoptotic mechanisms, including inhibition of intrinsic apoptosis pathway and JNK.
Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757, Korea.
Sang Heon
SH
Suh
Ko Eun
KE
Lee
Jeong Woo
JW
Park
In Jin
IJ
Kim
Ok
O
Kim
Chang Seong
CS
Kim
Joon Seok
JS
Choi
Eun Hui
EH
Bae
Seong Kwon
SK
Ma
Jong Un
JU
Lee
Soo Wan
SW
Kim
Apoptosis; Gentamicin; Kidney; Paricalcitol