대한신장학회

논문분류	춘계학술대회 초록집
제목	Benefical and anti-fibrotic effect of surface engineered nano-formulation of crocetin on experimental induced peritoneal fibrosis: novel approaches for peritoneal dialysis
저자	Deeksha Chauhan1, Vikas Kumar2
출판정보	2018; 2018(1):
키워드	Peritoneal dialysis \| crocetin \| TGF-β/Smad pathway \| nanoformulation \| anti-fibrotic
초록	Objectives: Peritoneal dialysis (PD) is widely accepted alternative to hemodialysis in the treatment of end stage renal disease. Recent studies suggest that PD is effective for initial two year on patient with renal replacement therapy and long term treatment can cause inflammation, fibrosis of peritoneal membrane (PM), neoangiogenesis etc. Activation of TGF-β/Smad pathway can lead to inflammation, neoangiogenesis important in alteration of PM with PD. Now, targeting the TGF-β singling pathway is consider as the novel approach to treat PD complications. Here, we investigated the beneficial effect of Crocetin (CT) in Wistar rat having peritoneal fibrosis (PF). Methods: Emulsion solvent technique was used for the preparation of CT loaded PLGA nanoperticles (CT-PLGA-NP). The CT-PLGA-NP was developed via cost-effective doses system and tested for their potential to reduce transforming growth factor-β (TGF-β) signalling via docking. Intraperitoneal injection of Chlorhexidine gluconate (0.1%) was used to induce the PF in rats. Inflammatory and biochemical parameters were scrutinized, respectively. Inmmunoflurescence and immunohistochemistry techniques were used for the estimation of fibrosis associated factor. Results: CT-PLGA-NP exhibited the a desired nono particles which are spherical and smooth in nature and relatively small size distribution. Docking analysis suggest that CT was snugly fitted into the inner grove of allosteric site of TGF-β via making selectively and efficiently interaction with ALA41, ILE22, VAL106 and VAL107 protein receptor protein with Ki ranging from 554 nm to 4.34 µM disclosing as potential effect. CT exhibited the considerably down-regulation of peritoneal membrane thickness and expression of myofibroblasts with avoidance of loss filtration of peritoneal membrane. CT significantly reduced the neoangiogenesis and proinflammatroy chemicals like TNF Alpha (72%), MCP -1 (52%) and IL- 1 Beta (48%) when compared to standard PG group. Conclusions: Crocetin down-regulated the experimental peritoneal fibrosis via alteration of TGF-β/Smad pathway and suggested the potential strategy for treating long term Peritoneal dialysis complications.
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