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
Cis-dichlorodiammine platinum II (Cisplatin), an effective chemotherapeutic agent, induces acute renal failure by unknown mechanisms. To investigate direct toxic effects of cisplatin on the renal proximal tubular transport system, LLC-PK-1 cell line was selected as a cell model and the sugar transport activity was evaluated during a course of cisplatin treatment. Cells grown to confluence were treated with cisplatin for 60 min, washed, and then incubated for up to 5 days. At appropriate intervals, cells were tested for sugar transport activity using alpha-methyl-D-(14C)glucopyranoside (AMG) as a model substrate. In cells treated with 100 micrometer cisplatin, the AMG uptake was progressively impaired after 3 days. The viability of cells was not substantially changed with cisplatin of less than 100 micrometer, but it decreased markedly with 150 and 200 micrometer. In cisplatin-treated cells, the Na+/-dependent AMG uptake was drastically inhibited with no change in the Na+/-independent uptake. Kinetic analysis indicated that Vmax was suppressed, but Km was not altered. The Na+/-dependent phlorizin binding was also decreased in cisplatin-treated cells. However, the AMG efflux from preloaded cells was not apparently retarded by cisplatin treatment. These data indicate that the cisplatin treatment impairs Na+/-hexose cotransporters in LLC-PK-1 cells and suggest strongly that defects in transporter function at the luminal plasma membrane of the proximal tubular cells constitute an important pathogenic mechanism of cisplatin nephrotoxicity.