The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Antiapoptotic Effect of Paricalcitol in Gentamicin-induced Kidney Injury

  • Suh, Sang Heon (Department of Internal Medicine, Chonnam National University Medical School) ;
  • Lee, Ko Eun (Department of Internal Medicine, Chonnam National University Medical School) ;
  • Park, Jeong Woo (Department of Internal Medicine, Chonnam National University Medical School) ;
  • Kim, In Jin (Department of Internal Physiology, Chonnam National University Medical School) ;
  • Kim, Ok (Department of Internal Physiology, Chonnam National University Medical School) ;
  • Kim, Chang Seong (Department of Internal Medicine, Chonnam National University Medical School) ;
  • Choi, Joon Seok (Department of Internal Medicine, Chonnam National University Medical School) ;
  • Bae, Eun Hui (Department of Internal Medicine, Chonnam National University Medical School) ;
  • Ma, Seong Kwon (Department of Internal Medicine, Chonnam National University Medical School) ;
  • Lee, Jong Un (Department of Internal Physiology, Chonnam National University Medical School) ;
  • Kim, Soo Wan (Department of Internal Medicine, Chonnam National University Medical School)
  • Received : 2013.06.28
  • Accepted : 2013.09.17
  • Published : 2013.10.30
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Abstract

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 ${\mu}g/kg/day$) 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.

Keywords

References

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