Zinc Oxide Nanoparticles Alleviate Cyclophosphamide Induced Hepatotoxicity in Male Albino Rats

Abstract

Background: Cyclophosphamide (CP) is a potent anticancer agent. Its clinical use is restricted because of its marked organ toxicity associated with increased oxidative stress and inflammation. Zinc oxide nanoparticles (nZnO) are one of the most abundantly used nanomaterials in consumer products and biomedical applications. Objectives: The aim of the present study was to evaluate the ameliorative effect of Zn-O nano-particles on hepatotoxicity induced by cyclophosphamide in male albino rats. Materials and Methods: Twenty four adult male rats (Sprague Dawley) were grouped randomly into four groups of six rats each. Group I. Control group: Received 0.2 ml saline /day i.p. injection for 14 days (day by day), group II (CP group): Received CP 20 mg/kg/day body weight (b.w.) day by day for 14 days by intraperitoneal injection, Group III (nZnO group): Received nZnO (5 mg/kg)/day b.w., intraperitoneally for 14 days. Group IV (CP + ZnO NPs group): Received nZnO group: Received nZnO (5 mg/kg/day) b.w., intraperitoneally for 14 days, plus CP 20 mg/kg/day body weight (b.w.) day by day for 14 days by intraperitoneal injection. At the end of the experimental period, rats were anesthetized using light ether. Blood and liver samples were taken and prepared for biochemical measurements and histological examination. Results: Serum total proteins, albumin, and globulin levels, were reduced in CP group when compared with the control group. In CP-animals treated with nZnO, these parameters were improved when compared with the CP-treated. A significant elevation in ALT, AST, ALP activities and total bilirubin concentration were observed after CP treatment as compared to vehicle treatment. Co administration of Pretreatment and nZnO with CP were reduced the enzyme activities and total bilirubin concentration significantly, as compared to CP-treated animals. Photomicrograph section of liver of nZnO-treated group showing hepatic lobule and hepatocytes surrounding a central vein and normal sinusoid. Liver of CP treated group reveals lobular infiltrate by chronic inflammatory cells congested hepatic sinusoids containing red blood cells with hepatocytes disarray and cloudy swelling, increased sinusoidal Kupffer cells, and hepatocytes with inculpated or triple nucleated. Photomicrograph of the section of liver of nZnO and CP combination group showed, decrease of the inflammation and infiltration of the portal area. Conclusion: It can be concluded that CP induced hepatotoxicity. Treatment of rats with zinc oxide nano-particles and CP together ameliorated the toxicity induced by CP. These results may provide further visions into proper treatment of patients by improving side effects of chemotherapy. However further studies are necessary to establish optimal doses of nZnO and receive the best safety profile.