Hepatotoxicity induced by intravenous administration of PEGylated nano-graphene oxide in albino mice

Abstract

Graphene oxide (GO) has been intensely investigated in recent years due to its biocompatibility and its role in drug delivery. Its conjugation with polyethylene glycol (PEG) further improves its solubility in physiological solutions, which is important for enhancing efficacy of drug delivery. The present study aimed to assess the hepatotoxicity of PEG-nGO in mature mice. Liver function tests such as Alanine transferase (ALT), Alkaline phosphatase (ALP) were performed in the liver homogenate of the control and treated groups after intravenous administration of a single dose (5 mg/kg) of PEG-nGO through the tail vein. Total Glycogen content and lactate dehydrogenase (LDH) activity was measured. For histology studies, liver slices were fixed in 10% formalin and stained with H&E and photographed. The liver function test indicated a significant increase in ALT and ALP activity following 1 to 2 h of treatment with PEG-nGO, which recovers to normal levels at 4 h. Total glycogen contents were mobilized from the liver in the first hour in response to stress, which again regain normality after 4 h. The LDH assay showed maximum necrosis and apoptosis of hepatocytes at 1 h. Histology studies further indicated that infiltration of inflammatory cells and vacuolization of cytoplasm occurred mostly at 1 h. PEG-nGO treatments caused maximum damage and toxicity to the liver during the first 2 h. Following this, the liver tissues recover substantially which indicated that the low dose toxicity of PEG-nGO to the liver was transient and reversible.