Abstract: TH-PO247

Omega-3 Fatty Acids Attenuate Cisplatin Nephrotoxicity via Enhancement of Autophagy Flux

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Ham, Youngrok, Chungnam National University , Daejeon, Korea (the Republic of)
  • Jeong, Jin young, Chungnam National University, Daejeon, Korea (the Republic of)
  • Bae, Hong jin, Chungnam National University , Daejeon, Korea (the Republic of)
  • Song, Chang hun, Chungnam National University , Daejeon, Korea (the Republic of)
  • Na, Kiryang, Chungnam national university, Deajeon, Korea (the Republic of)
  • Lee, Kang Wook, Chungnam National University , Daejeon, Korea (the Republic of)
  • Kim, Jwajin, Chungnam national university, Deajeon, Korea (the Republic of)
  • Lee, Jiwon M., Chungnam National University, Daejeon, Korea (the Republic of)
  • Choi, Dae Eun, Chungnam National University , Daejeon, Korea (the Republic of)
Background

Various studies demonstrated that omega-3 polyunsaturated fatty acids (PUFAs) attenuate kidney injuries through anti-apoptotic and antioxidant properties. Recently, several studies showed that omega-3 PUFAs enhance induction of autophagy. We evaluated whether administration ω-3 PUFAs may induce autophagy in cisplatin nephrotoxicity, and investigated the role of autophagy in attenuating cisplatin nephrotoxicity by ω-3 PUFAs.

Methods

10-week- old male C57BL/6 mice were divided into 4 groups; control, control plus omega 3, cisplatin, cisplatin plus omega 3; they were injected with a vehicle or single dose of cisplatin (16 mg/kg body weight) intraperitoneally. Omega 3 and vehicle were administered orally using an NG tube (Omega 32,000 μg/kg/day) from pre-injection day to 3 days after injection of cisplatin. Mice were sacrificed at 4 days after administration of cisplatin and kidney tissue were collected. Real time PCR, western blot and immunohistochemistry for molecular study and H&E stain and PAS stain for histologic examination were performed.

Results

Omega 3 treated cisplatin-mice showed improvement of renal cell survival, renal function,and pathologic damage compared to vehicle treated cisplatin-mice. Omega-3 treatment also reduced the renal expression of MCP-1 (Monocytye chemotactic protein-1) and OPN (Osteopontin) in cisplatin-treated kidney. Cisplatin-mice kidney showed that higher amounts of LC3, Beclin-1 and p62 compared to sham mice. Omega 3 treated cisplatin kidney showed higher amounts of LC3 and Beclin-1 and lower amounts of p62 compared to vehicle treated cisplatin kidney. Moreover, renal cathepsin D and ATP6E were also increased in omega 3 treated cisplatin-mice compared to vehicle treated cisplatin-mice.

Conclusion

Omega 3 fatty acids attenuate renal injury in cisplatin nephrotoxicity through stimulating autophagy flux