Renoprotective potential of myo-inositol on diabetic kidney disease: Focus on the role of the PINK1/Parkin pathway and mitophagy receptors.

Recent studies have emphasized the role of mitochondria in renal function as well as in renal injury. Poor mitochondrial quality control mechanisms including mitochondrial fusion, fission and mitophagy are major contributors for progression of diabetic renal injury. The current study is aimed to evaluate the protective role of myo-inositol (MI) against diabetic nephropathy (DN) by utilizing high glucose exposed NRK 52E cell and streptozotocin (STZ) induced DN model. MI supplementation (at doses 37.5 and 75 mg/kg) ameliorated albuminuria and enhanced the renal function as indicated significant improvement in urinary creatinine and urea levels. On the other hand, the western blot analysis of both in vitro and in vivo studies has revealed poor mitophagy in renal cells which was reversed upon myo-inositol treatment. Apart from targeting the canonical PINK1/Parkin pathway, we also focused on the role mitophagy receptors prohibitin (PHB) and NIP3-like protein (NIX). A significant reduction in expression of NIX and PHB2 was observed in renal tissue of diabetic control rats and high glucose exposed NRK 52E cells. Myo-inositol treatment resulted in positive modulation of PINK1/Parkin pathway as well as PHB2 and NIX. Myo-inositol also enhanced the mitochondrial biogenesis in renal tissue of diabetic rat by upregulating Nrf2/SIRT1/PGC-1α axis. The current study thus underlines the renoprotective effect myo-inositol, upregulation of mitophagy proteins and mitochondrial biogenesis upon myo-inositol treatment.