ABSTRACT
Objective:To study the renal toxic effect of titanium dioxide nanoparticles (TiNPs)prepared by chemical and green route.Methods:TiNPs were prepared by chemical (sol gel technique) and green route (using aqueous extract of Desmodium gangeticum root by using titanium tetraisopropoxide as precursor).Thus prepared TiNPs were characterized using UV-visible spectrophotometry,X-ray diffractometry and evaluated its renal toxic impact in different experimental models viz.,Wistar rats (100 mg/kg b.wt.;oral),LLC-PK1 cells (100 mg/mL) and isolated renal mitochondria (0.25,0.5 and 1 mg/mL).Results:Compared to the chemically synthesized TiNPs,Desmodium gangeticum synthesized nanoparticles showed less nephrotoxicity,determined by elevated serum renal markers like urea (62％),creatinine (35％),aspartate aminotransferase (61％) and alanine transaminase (37％) and the result was in agreement with cellular toxicity (measured by MTT assay and lactate dehydrogenase activity).Further toxicity evaluation at the level of mitochondria showed not much significant difference in TiNPs effect between two synthetic routes.Conclusions:The biochemical findings in renal tissue and epithelial cell (LLC-PK1)supported by histopathology examination and isolated mitochondrial activity showed minor toxicity with TiNPs prepared by green route (TiNP DG) than TiNP Chem.
ABSTRACT
Objective To study the renal toxic effect of titanium dioxide nanoparticles (TiNPs) prepared by chemical and green route. Methods TiNPs were prepared by chemical (sol gel technique) and green route (using aqueous extract of Desmodium gangeticum root by using titanium tetraisopropoxide as precursor). Thus prepared TiNPs were characterized using UV–visible spectrophotometry, X-ray diffractometry and evaluated its renal toxic impact in different experimental models viz., Wistar rats (100 mg/kg b.wt.; oral), LLC-PK1 cells (100 mg/mL) and isolated renal mitochondria (0.25, 0.5 and 1 mg/mL). Results Compared to the chemically synthesized TiNPs, Desmodium gangeticum synthesized nanoparticles showed less nephrotoxicity, determined by elevated serum renal markers like urea (62%), creatinine (35%), aspartate aminotransferase (61%) and alanine transaminase (37%) and the result was in agreement with cellular toxicity (measured by MTT assay and lactate dehydrogenase activity). Further toxicity evaluation at the level of mitochondria showed not much significant difference in TiNPs effect between two synthetic routes. Conclusions The biochemical findings in renal tissue and epithelial cell (LLC-PK1) supported by histopathology examination and isolated mitochondrial activity showed minor toxicity with TiNPs prepared by green route (TiNP DG) than TiNP Chem.
ABSTRACT
Renal clearance is a key determinant of the elimination of drugs. To date, only few in vitro-in vivo extrapolation (IVIVE) approaches have been described to predict the renal organ clearance as the net result of glomerular filtration, tubular secretion, and tubular reabsorption. In this study, we measured in LLC-PK1 cells the transport of 20 compounds that cover all four classes of the Biopharmaceutical Drug Disposition System. These data were incorporated into a novel kidney model to predict all renal clearance processes in human. We showed that filtration and secretion were main contributors to the renal organ clearance for all compounds, whereas reabsorption was predominant for compounds assigned to classes 1 and 2. Our results suggest that anionic drugs were not significantly secreted in LLC-PK1 cells, resulting in under-predicted clearances. When all study compounds were included a high overall correlation between the reported and predicted renal organ clearances was obtained (R² = 0.83). The prediction accuracy in terms of percentage within twofold and threefold error was 70% and 95%, respectively. In conclusion, our novel IVIVE method allowed to predict the human renal organ clearance and the contribution of each underlying process.