Effects of Amifostine on Liver Oxidative Stress Caused by Cyclophosphamide Administration to Rats

Abstract

Cyclophosphamide is an inactive cytostatic, which is metabolised into active metabolites mainly in the liver. During bioactivation, reactive oxygen species (ROS) are also formed, which can modify the components of both healthy and neoplastic cells leading to decreased antioxidative capacity. Amifostine is a drug that can inactivate ROS. The aim of the present study was to evaluate the influence of amifostine on the antioxidative system of the liver of rats exposed to cyclophosphamide. Intraperitoneal administration of cyclophosphamide was found to decrease the activity of liver antioxidative enzymes, i.e. superoxide dismutase, glutathione peroxidase and glutathione reductase, and to increase catalase activity. Amifostine slightly influenced antioxidative enzyme activity, causing a significant increase only in superoxide dismutase activity. Co-administration of cyclophosphamide and amifostine nearly prevented changes in activities of superoxide dismutase, glutathione reductase and catalase, as well as to a high degree of glutathione peroxidase. Cyclophosphamide also evoked a decrease in the level of non-enzymatic antioxidants, such as reduced glutathione and vitamins C, E and A, as well as total antioxidant status. Administration of amifostine alone caused a significant increase in non-enzymatic antioxidant level that resulted in an increase in total antioxidant status. Administration of amifostine together with cyclophosphamide to a large extent prevented changes in the evaluated non-enzymatic antioxidative parameters, decreasing values of their concentration to the values of control group. Changes of liver antioxidative abilities during detoxification of cyclophosphamide were accompanied by intensified lipid peroxidation, manifested by an increase in concentration of products such as malondialdehyde and 4-hydroxynonenal. Amifostine caused the inhibition of lipid peroxidation in the liver of both control and cyclophosphamide-treated rats. In conclusion, our results suggest that amifostine significantly protects liver antioxidant properties from changes caused by cyclophosphamide treatment and in consequence prevents oxidative stress and phospholipid peroxidative damage.

Modulation of cyclophosphamide-induced early lung injury by allicin

“…This observation is in line with many reports that demonstrated apparent elevation in lung TBARS following administration of CP (Patel, 1987;Venkatesan & Chandrakasan, 1995;Stankiewicz et al, 2002). Increased TBARS level observed following CP administration in the current work could be indirectly attributed to the decreased level of GSH; also CP has been proved to induce significant alterations in the activity of NADH and NADPH2, likely to be responsible for the ultrastructural changes within mitochondria which include features of mitochondrial damage with disruption of mitochondrial membranes.…”

The Protective Effects of Amifostine on Adriamycin-Induced Acute Cardiotoxicity in Rats

“…In the present study, adriamycin significantly decreased the GSH levels, but the GSH levels were significantly higher in the amifostine-pretreated group than controls. It has been reported that amifostine increased GSH levels in rats (Issels and Nagele 1989;Dorr et al 1996;Stankiewicz et al 2002). So, amifostine may have favorable effects on adriamycininduced acute cardiotoxicity.…”

Protective effects ofOriganum vulgareethanol extract against cyclophosphamide-induced liver toxicity in mice

“…Phosphoramide mustard is believed to have antineoplastic activity, but acrolein, a highly reactive metabolite with a short biological half-life, may be responsible for CP-induced liver damage (Honjo et al, 1988). Recent studies suggest that CP generates reactive oxygen species (ROS), such as the superoxide anion, hydroxyl radical and hydrogen peroxide (H 2 O 2 ), during its oxidative metabolism and suppresses the liver's antioxidant defense mechanisms (Bhattacharya et al, 2003;Stankiewicz et al, 2002).…”