Influence of early trace element and vitamin E supplements on antioxidant status after major trauma: a controlled trial

Abstract

Negative selenium and zinc balances occur after major trauma, potentially compromising antioxidant defenses. The aim of this study was to determine if micronutrient supplementation could modulate the blood antioxidant status. 32 patients admitted to surgical ITU with major trauma were randomized to receive either selenium alone, selenium plus copper, zinc and tocopherol, or placebo for 5 days after injury. Blood samples were collected on days 0, 1, 2, 5, 10 and 20 and analyzed for plasma selenium, copper, zinc, tocopherol, glutathione peroxidase and total antioxidant capacity (TAC), and for erythrocyte antioxidant enzymes. Plasma selenium and tocopherol concentrations were low on admission, but increased significantly (p = 0.001) with supplementation, whereas there was an early significant fall in TAC (p < 0.002) in the selenium supplemented groups. Plasma glutathione peroxidase activity increased significantly between days 2 and 5 with supplementation (p = 0.02), but erythrocyte enzyme activity was unaffected. The unexpected early fall in plasma TAC with supplementation may reflect mobilization of antioxidant defenses.

Introduction

After major injury, patients develop characteristic endocrine, immune and metabolic alterations. The inflammatory process is intense, and septic complications are frequent. The free radical and reactive oxygen species (ROS) production is markedly increased as a consequence of stimulation of leukocytes by cytokines, numerous mediators, bacterial products, and opsonised material or contact with unusual surfaces [1]. Excessive ROS production can lead to cellular damage and death by oxidizing lipid membranes, proteins, nucleic acids and carbohydrates [2]. Moreover, severely injured patients frequently suffer hypoxia and hypovolemic shock, which favor an intracellular accumulation of hypoxanthine. Upon restoration of perfusion and oxygen delivery to cells, hypoxanthine is oxidized, generating further ROS, further compromising the intrinsic antioxidant defense: this cascade promotes extension of the initial injury [2], [3], [4].

The endogenous antioxidants include micronutrients, which may be direct antioxidants or have indirect effects as part of antioxidant enzymes. Among the trace elements, selenium (Se) is an essential component of the glutathione peroxidases (GSHPx) a family of primary antioxidant enzymes, while copper (Cu) and zinc (Zn) are structural components of CuZn superoxide dismutase (SOD), Zn being also part of catalase. Vitamins such as alpha-tocopherol have major roles in lipid membrane protection. Determination of the numerous individual antioxidants is almost impossible [5]. The assessment of total plasma antioxidant capacity (TAC) as a single measurement has merit if it is accepted that antioxidants can act synergistically [6], and has raised considerable interest [7]. The principal contributors to TAC measured here (with approximate % contribution) are albumin (43%), urate (33%), ascorbate (9%), alpha-tocopherol (3%), bilirubin (2%), and other antioxidants (10%).

Before injury, most trauma patients are presumed healthy and free of micronutrient deficiency. Nevertheless, the plasma levels of many vitamins and trace elements including selenium are frequently depressed upon admission to the ICU [8]. In a previous study, we showed that Se and Zn status undergo extensive and long-lasting changes starting early after trauma, associated with negative balances during the first week after injury [8]. Initial trauma resuscitation frequently requires large volumes of crystalloids, which result in a variable degree of hemodilution, and contributes to low plasma levels. Further, the acute phase response, which develops very quickly [9], [10], can reduce circulating levels, via a redistribution of Se, Zn and iron to high priority organs [4]. Micronutrient losses with negative balances further decrease blood levels [8]. Finally, although trauma patients are presumed free of prior deficiency, studies have shown that the Se status particularly is suboptimal in a large portion of the healthy population in various European countries [11]. While the initial decrease in circulating trace element concentrations probably only has limited consequences, changes persisting beyond 24–48 hours may have deleterious effects. However, the relationship between the acute changes in micronutrient status and the antioxidant defense is not yet established in the critically ill trauma patient.

The present study was aimed at assessing the effect of Se supplementation alone or in association with Cu, Zn and vitamin E upon markers of antioxidant function in patients with major trauma.