Reactive oxygen species, antioxidant mechanisms and serum cytokine levels in cancer patients: impact of an antioxidant treatment

Abstract

Objective. So far, it is not well established whether oxidative stress found in cancer patients results from an increased production of oxidants in the body or from a failure of physiological antioxidant systems. To further investigate this question we have assessed the blood levels of reactive oxygen species as a marker of free radicals producing oxidative stress and the most relevant of the physiological body enzymes counteracting reactive oxygen species, namely glutathione peroxidase and superoxide dismutase. Serum levels of proinflammatory cytokines and IL‐2 were also investigated. All these parameters were studied in relation to the clinically most important index of disease progression, namely Performance Status (ECOG PS). We also tested the reducing ability of different antioxidant agents on reactive oxygen species levels by measuring the increase in glutathione peroxidase activity, and the reduction of serum levels of IL‐6 and TNF. Design, setting and subjects. We carried out an open non randomized study on 28 advanced stage cancer patients (stage III, 10.7%, and stage IV, 89.3%) with tumours at different (8) sites: all were hospitalized in the Medical Oncology Dept, University of Cagliari Interventions. The patients were divided into 5 groups and a different antioxidant treatment was administered to each group. The selected antioxidants were: alpha lipoic acid 200 mg/day orally, N‐acetylcysteine 1800 mg/day i.v. or carboxycysteine‐lysine salt 2.7 g/day orally, amifostine 375 mg/day i.v., reduced glutathione 600 mg/day i.v., vitamin A 30000 IU/day orally plus vitamin E 70 mg/day orally plus Vitamin C 500 mg/day orally. The antioxidant treatment was administered for 10 consecutive days. Results. Our results show that all but one of the antioxidants tested were effective in reducing reactive oxygen species levels and 2 of them (cysteine‐containing compounds and amifostine) had the additional effect of increasing glutathione peroxidase activity. Comprehensively, the “antioxidant treatment” was found to have an effect both on reactive oxygen species levels and glutathione peroxidase activity. The antioxidant treatment also reduced serum levels of IL‐6 and TNF. Patients in both ECOG PS 0‐1 and ECOG PS 2‐3 responded to antioxidant treatment.

Increased ROS generation and p53 activation in α-lipoic acid-induced apoptosis of hepatoma cells

“…Dietary supplements and endogenous antioxidants can interfere with these processes [4][5][6]. Among agents with antioxidant effect, α-LA, a natural occurring substance, has been reported to have a beneficial effect in patients with advanced cancer by increasing the glutathione peroxidase activity and by reducing oxidative stress [7,8]. Furthermore, several studies demonstrated that α-LA had a wide range of pharmacological properties acting to prevent many degenerative diseases, such as diabetic polyneuropathy, and has been described as a therapeutic agent in a number of conditions related to liver diseases, including alcohol-induced damage, mushroom poisoning, metal intoxication, CCl 4 poisoning and hyperdynamic circulation in biliary cirrhosis [9][10][11].…”

Oxidative stress in lymphocytes, neutrophils, and serum of oral cavity cancer patients: modulatory array of l-glutamine

“…Any changes in one of these systems may break this equilibrium and cause cellular damages and, ultimately, malignant transformation [13,47]. It has been reported that ROS production is pathologically high in advance-stage cancer patients [27,28]. Glutathione peroxidase (GPx), one of the major antioxidant enzymes in glutathione antioxidant defense system, showed significantly lower value in cancer patients as compared to control [27,28,38].…”

“…It has been reported that ROS production is pathologically high in advance-stage cancer patients [27,28]. Glutathione peroxidase (GPx), one of the major antioxidant enzymes in glutathione antioxidant defense system, showed significantly lower value in cancer patients as compared to control [27,28,38]. Moreover, these anti-oxidants, both natural and synthetic, neutralize metabolic products (including reactive oxygen species), interfere with activation of procarcinogens, prevent binding of carcinogens to DNA, inhibit chromosome aberrations, restrain replication of the transformed cell, suppress actions of cancer promoters, and may even induce regression of precancerous oral lesions [12].…”

Antioxidative Properties of Fish Protein Hydrolysates

“…The production of reactive oxygen species (ROS) in living systems causes oxidative stress and is associated with various disease conditions such as cancer and cardiovascular diseases [74,75]. Oxidative stress can be alleviated by the consumption of antioxidant-rich foods.…”