title: Organic solvent-induced proximal tubular cell apoptosis via caspase-9 activation.
abstract: Long-term exposure to solvents is associated with apoptosis, which is implicated in the development and progression of tubulo-interstitial fibrosis and chronic renal failure. In our previous study, we demonstrated that toluene and p-xylene as the most commonly used organic solvents induced proximal tubular cells apoptosis. This study was conducted to assess the apoptotic pathway of toluene and p-xylene induced proximal tubular apoptosis. This was assessed by measuring the caspase-9 activity LLC-PK1 cells exposed to both compounds. A model of proximal tubular cell (LLC-PK1) cytotoxicity exposed to 1mM of either p-xylene or toluene was compared to untreated control for caspase-9 activity and Bax/Bcl-2 protein level. Furthermore, DNA fragmentation in the presence of caspase-9 inhibitor (Z-LEHD-FMK) in a dose-dependent manner was assessed. Both compounds induced caspase-9 activity, which was accompanied by up-regulation of Bax, whereas Bcl-2 level did not change. DNA fragmentation induced by both solvents was inhibited by caspase-9 inhibitor in dose-dependent manner. This data suggest that p-xylene or toluene induces nephrotoxicity via mitochondrial caspase-9 pathway. This mechanism involves up-regulation of the apoptotic protein, Bax.
authors.affiliation: Department of Experimental Medicine & Nephrology, St. Bart's & Royal London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Saeed S
authors.initials: SS
authors.lastname: Al-Ghamdi
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Raftery
authors.forename: Muhammad M
authors.initials: MM
authors.lastname: Yaqoob