Renal clearance of graphene oxide: glomerular filtration or tubular secretion and selective kidney injury association with its lateral dimension

Abstract

Background Renal excretion is one of the major routes of nanomaterial elimination from the body. Many previous studies have found that graphene oxide nanosheets are excreted in bulk through the kidneys. However, how the lateral size affects GO disposition in the kidneys including glomerular filtration, active tubular secretion and tubular reabsorption is still unknown. Results The thin, two-dimensional graphene oxide nanosheets (GOs) was observed to excrete in urine through the kidneys, but the lateral dimension of GOs affects their renal clearance pathway and renal injury. The s-GOs could be renal excreted via the glomerular filtration, while the l-GOs were predominately excreted via proximal tubular secretion at a much faster renal clearance rate than the s-GOs. For the tubular secretion of l-GOs, the mRNA level of basolateral organic anion transporters Oat1 and Oat2 in the kidney presented dose dependent increase, while no obvious alterations of the efflux transporters such as Mdr1 and Mrp4 mRNA expression levels were observed, suggesting the accumulation of l-GOs. During the GO renal elimination, mostly the high dose of 15 mg/kg s-GO and l-GO treatment showed obvious kidney injuries but at different renal compartment, i.e., the s-GOs induced obvious glomerular changes in podocytes, while the l-GOs induced more obvious tubular injuries including necrosis of renal tubular epithelial cells, loss of brush border, cast formation and tubular dilatation. The specifically tubular injury biomarkers KIM1 and NGAL were shown slight increase with mRNA levels in l-GO administrated mice. Conclusions This study shows that the lateral size of GOs affected their interactions with different renal compartments, renal excretion pathways and potential kidney injuries.

A microphysiological system for handling graphene related materials under flow conditions

“…40–45 Meanwhile, in vivo studies performed with animal models have shown that GRMs tend to accumulate throughout the organism, mainly in the liver, lungs, spleen and kidney, thus resulting in varying degrees of damage to these organs. 46–52…”

“…To confirm these results, a renal proximal tubular cell line (HK-2) was used and the uptake of l-GO was found to be higher than s-GO after 4 and 24 hours of graphene exposure for HK-2 cells in traditional cell culture. 49…”

“…[40][41][42][43][44][45] Meanwhile, in vivo studies performed with animal models have shown that GRMs tend to accumulate throughout the organism, mainly in the liver, lungs, spleen and kidney, thus resulting in varying degrees of damage to these organs. [46][47][48][49][50][51][52] In the specific case of renal cell studies, cells have shown that their viability presents a dose-dependent cytotoxic effect when human embryonic kidney cells were seeded using traditional cell culture and were kept under static conditions after GO exposure. 53 This cell line showed no significant toxicity when cell cultures were exposed to GO at sublethal concentrations of up to 10 mg mL À1 under static conditions.…”

Environmental and Health Impacts of Graphene and Other Two-Dimensional Materials: A Graphene Flagship Perspective

“…The detoxifying enzyme catalase was decreased whereas levels of the oxidative stress marker malondialdehyde were increased in tissue homogenates. Both GO dose and lateral dimension affected renal excretion pathways and kinetics as well as extent of kidney injuries in CD1 mice . The small GO materials (162 nm) were eliminated via glomerular filtration and induced structural alterations in glomerular podocytes while larger GO materials (330 nm) were eliminated faster via the proximal tubules.…”

“…Both GO dose and lateral dimension affected renal excretion pathways and kinetics as well as extent of kidney injuries in CD1 mice. 304 The small GO materials (162 nm) were eliminated via glomerular filtration and induced structural alterations in glomerular podocytes while larger GO materials (330 nm) were eliminated faster via the proximal tubules. At 15 mg/kg and both 2 and 7 days, both materials injured renal tubular epithelial cells, causing loss of brush border, cast formation and tubular dilatation, as well as increased glomerular diameter.…”