Hepatotoxicity and chromosomal abnormalities evaluation due to single and repeated oral exposures of chromium oxide nanoparticles in Wistar rats

Abstract

Metal oxide nanoparticles (NPs) have widespread uses ranging from nanoelectronics to nanotherapeutics. Because of their expanding industrial applications, a better understanding of their toxicity is needed. So far, limited reports are available on chromium oxide NPs (Cr2O3 NPs) toxicity. In this work, Cr2O3 NPs were synthesized and characterized in a sequential manner using X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy. Dose- and time-dependent toxicity assessment of Cr2O3 NPs was carried out in Wistar rats by examining liver function biomarkers, tissue histopathology, micronuclei (MN) formation, and chromosomal aberrations (CAs) in bone marrow along with sperm abnormalities. The results of this study demonstrated typical XRD and FTIR patterns of Cr2O3 NPs with a size of approximately 23.47 nm. Animals exposed to Cr2O3 NPs, exhibited a significant increase in aspartate transaminase, alanine transaminase, alkaline phosphatase, gamma glutamyltransferase, and total bilirubin, signifying liver injury. Histopathology data also supported the marked alterations in the liver biochemistry of NPs-exposed animals. Further, an increase in the frequency of MN, CA, and sperm abnormalities suggested Cr2O3 NPs-mediated genotoxicity. It is, therefore, suggested that possible safety issues of Cr2O3 NPs should be addressed promptly with limited future use in occupational settings.

Molecular mechanism of nanomaterials induced liver injury: A review

“…Chromium oxide nanoparticles: The investigated liver function biomarkers (ALT, AST, ALP, γgamma glutamyl transferase, total bilirubin levels) get elevated in a dose and exposure time-dependent fashion in rats after orally consuming Cr 2 O 3 -NPs. Routine histological examination clearly showed moderate to severe architectural damage including liver cell degeneration, Kupffer cell hyperplasia, parenchymal distortions, dilated central vein, and hemorrhage for both low and high doses, indicating the role of chromium oxide-NPs in liver toxicity[ 23 ].…”

Hepatotoxicity induced by nanomaterials: mechanisms and in vitro models

“…16 ALPalkaline phosphatase; ALTalanine aminotransferase; ASTaspartate aminotransferase; -GTgamma glutamyl transferase; HIF-1hypoxia inducing factor 1 alpha; miR -microRNA; MMPmitochondrial membrane permeability; NADHreduced nicotinamide adenine dinucleotide; NADPH -NADH phosphate; NDmechanism of hepatotoxicity not described; NPnanoparticles; TACtotal antioxidant capacity; TBiltotal bilirubin; TEM transmission electron microscopy; TOStotal oxidative status; XRD -X-ray diffraction More recently, hepatotoxic effects were reported for chromium oxide (Cr2O3) NPs following oral administration to Wistar rats (Fatima and Ahmad 2019). Hepatic damage was confirmed by increased ALT, AST, ALP and gamma-glutamyl transferase serum levels, together with histological alterations.…”

“…-Dose and exposure duration-dependent hepatotoxicity - ALT, AST, ALP, -GT, TBil -Severe hemorrhage, hepatocyte degeneration, parenchymal distortions, dilated central vein, infiltration inflammatory cells ND(Fatima and Ahmad 2019) …”