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Evaluation of genotoxic and hepatotoxic effects of graphene oxide nanosheets in male albino mice

Walaa Nasr Abd El Mohsen Mohamed; Taher Ahmed Salah El Din; Amany Abd El- Monem Tohamy; Nabil Ahmed El-yamany; Adel Sayed Amin.

Abstract
Graphene oxide Nano-sheets (GOs) have a wide range of industrial, biochemical and medical applications regarding their unique physical, chemical and biocompatibility properties. For assessment of toxicological potential of graphene oxide nanosheets ninety male mice were divided into six groups; the control and five treated groups: animals of the control group received an intraperitoneal (i.p) injection of 0.2 ml saline solution (0.9% NaCl) once weekly for eight weeks. The treated groups were received an i.p injection of 10, 50, 100, 250, and 500 µg GOs/kg body weight once weekly, for eight weeks. Animals of all groups were sacrificed after 7, 28, and 56-days post treatment. The present study was conducted to evaluate the genotoxic effects of GOs on mice liver cells using alkali comet assay. In addition, physiological investigations and description of hepatic histopathological alternations were carried out. Results revealed that GOs induced DNA damage (DNA fragmentation), represented in dose and time-dependent increase in % tail DNA migration, tail moment and comet tail length. As well as, a diminish in % head DNA in nuclei of liver of GOs-treated mice versus control groups. The effect of GOs on hepatic superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) level indicated slight decrease at low doses (10 and 50 µg) at all time intervals of experimental period as compared to the control groups. The administration of high doses of GOs (100, 250, and 500 µg) indicated a significant diminish in SOD, CAT activities and decrease in GSH level; with subsequent elevation in malondialdehyde (MDA) levels in liver as compared to control groups. Various hepatic histopathological alternations were dose and time dependent in GO-treated mice versus control. In conclusion, the induction of DNA fragmentation in liver denoting the genotoxicity of GOs in dose and time dependent manner. GOs had the ability for inducing various hepatic alternations in a dose and time dependent manner indicating cytotoxicity presumably by oxidative stress. Thus, GOs should be used under strict control and these serious side effects should be taken into consideration when used in vivo treatments.

Key words: Albino mice;Graphene oxide nanosheets;Comet Assay;Oxidative stress;Hepatocellular histopathology



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