Pharmaceutica Analytica Acta

4-Phenylbutyrate protects renal proximal tubular cells from palmitic acid-induced endoplasmic reticulum stress and cell death

5^th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems

March 16-18, 2015 Crowne Plaza, Dubai, UAE

Shankar Munusamy, Dania Alkhiyami, Souad Berzou, Atefeh Moeinzadeh and Hebatalla Mohamed

Posters & Accepted Abstracts: Pharm Anal Acta

Abstract:

Obesity is implicated as a significant risk factor for chronic kidney disease (CKD). High plasma free fatty acid levels observed with obesity impairs the endoplasmic reticulum (ER) and cause ER stress. Chemical chaperones, which relieve ER stress, such as 4-phenylbutyrate (4-PBA) have been shown to protect the liver and pancreas against obesity-induced organ damage; however, their protective role in obesity-induced renal damage is unknown. Thus, we investigated the nephroprotective role of 4-PBA in an in vitro model of palmitic acid (PA)-induced ER stress and renal injury using normal rat kidney cells (NRK- 52E). Cells were divided into four groups: Control, 250 μM PA-treated, 5 mM 4-PBA-treated, and 4-PBA+PA co-treated. After 24 h of PA and/or 4-PBA treatments, cell viability and caspase-3/7 activity (a marker of apoptosis) were determined. Immunoblot analyses were performed to quantitate the levels of ER stress markers - glucose-regulated protein (GRP78) and C/ EBP homologous protein (CHOP) - in renal cells. Exposure to PA significantly reduced the viability (81.3% to that of control) in NRK-52E cells, and markedly increased the activity of caspase-3/7 activity (2-fold increase over control) and the expression of ER stress markers GRP78 and CHOP (1.6 and 2 folds over control respectively) at P-value <0.05. Intriguingly, cells treated with 4-PBA were protected from PA-induced ER stress and apoptotic cell death. Our studies demonstrate that 4-PBA acts as nephroprotectant and prevents fatty acid induced ER stress and apoptosis in renal cells. Further investigations in vivo are required to validate the therapeutic potential of 4-PBA to protect the kidney and prevent the development of CKD during obesity.