Dexmedetomidine acts as an oxidative damage prophylactic in rats exposed to ionizing radiation

doi:10.1016/j.jclinane.2016.06.031

Journal of Clinical Anesthesia

Volume 34, November 2016, Pages 577-585

https://doi.org/10.1016/j.jclinane.2016.06.031 Get rights and content

Highlights

•
Ionizing radiation causes oxidative stress by increasing oxidative metabolites and decreasing antioxidant defense mechanisms.
•
Dexmedetomidine provides protection from the oxidative stress caused by ionizing radiation.
•
High dose of dexmedetomidine provides better protection in lung and hepatic tissue.

Abstract

Study objective

To investigate the effects of dexmedetomidine on oxidative injury caused by ionizing radiation.

Design

Randomized controlled experimental study.

Setting

Department of radiation oncology and research laboratory of an academic hospital.

Interventions

Twenty-eight rats were randomized to 4 groups (n = 7 per group). Group S rats were administered physiologic serum; group SR rats were administered physiologic serum and 10 Gy external ionizing radiation. Groups D100 and D200 were administered 100 and 200 μg/kg dexmedetomidine intraperitoneally, respectively, 45 minutes before ionizing radiation.

Measurements

Liver, kidney, lung, and thyroid tissue and serum levels of antioxidant enzymes (glutathione peroxidase [GPX], superoxide dismutase, and catalase) and oxidative metabolites (advanced oxidation protein products, malondialdehyde, and nitrate/nitrite, and serum ischemia-modified albumin) were measured 6 hours postprocedure.

Main results

In group SR, IR decreased antioxidant enzyme levels and increased oxidative metabolite levels (P < .05). In plasma, antioxidant enzyme levels were higher and oxidative metabolite levels were lower in groups D100 and D200 than in group SR (P < .01). In tissues, hepatic and lung GPX levels were higher in groups D100 and D200 than in group SR (P < .001). Renal and thyroid GPX levels were higher in D200 than in group SR (P < .01). Thyroid superoxide dismutase levels were higher in groups D100 and D200 than in group SR (P < .01). Renal, lung, and thyroid catalase levels were higher in group D200 than in group SR (P < .01). Hepatic, renal, and lung advanced oxidation protein products and malondialdehyde levels were lower in groups D100 and D200 than in group SR (P < .01). Hepatic, renal, and lung nitrate/nitrite levels were lower in group D200 than in group SR (P < .05).

Conclusions

Dexmedetomidine preserves the antioxidant enzyme levels and reduces toxic oxidant metabolites. Therefore, it can provide protection from oxidative injury caused by ionizing radiation.

Introduction

People are often exposed to radiation during medical or paramedical procedures. Ionizing radiation is used for surgery, angiography, and several imaging protocols. It is also frequently used as a cancer treatment. However, these procedures can produce unwanted adverse effects. The basic mechanism of action for ionizing radiation is DNA damage that induces cell death [1]. Ionizing radiation creates reactive oxygen species (ROSs) through water ionization and subsequent reactions with chemicals in the immediate cellular environment. ROSs react with membrane lipids, proteins, and DNA, which is lethal to cells [2], [3]. In addition, ROSs negatively impact antioxidant defense mechanisms in cells by reducing the activity of antioxidant enzymes, especially glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) [3], [4]. Moreover, some destructive oxidative species, such as advanced oxidation protein products (AOPP), malondialdehyde (MDA), nitrite/nitrate (N/N), and ischemia-modified albumin (IMA), are produced during ionizing radiation reactions. Several recent studies have investigated methods to minimize oxidative damage [2] induced by ionizing radiation [2], [5], [6], [7], [8]. Reducing the amount of ionizing radiation the patient is exposed to is one method of minimizing damage; however, this technique is not a viable damage-reduction method for cancer radiotherapy due to negative effects on tumor response. Antioxidant drugs are another damage-reduction method because they inhibit ROS formation or inactivate ROSs after ionization has occurred.

Anesthetics [9] and anesthesia methods are frequently used during procedures involving radiation, such as radiotherapy [10], invasive imaging applications, or surgery under anesthesia [11]. Several urologic and orthopedic surgical procedures and invasive interventional procedures are performed with radiation imaging. Sedoanalgesia, which combines sedation and analgesia, is commonly used for these types of procedures [11]. For example, sedoanalgesia is frequently used when implanting catheters for high-dose radiation brachytherapy [12]. Dexmedetomidine, an α₂ adrenergic receptor agonist, has sedative, anxiolytic, and analgesic effects. Thus, it is ideal for sedoanalgesia procedures [10]. Dexmedetomidine has been shown to have antioxidant properties in experimental studies [13], and 1 study showed that dexmedetomidine enhanced the SOD activity of human blood [14].

In this randomized prospective study, we investigated the effects of dexmedetomidine on ionizing radiation damage. To this end, we measured the plasma and tissue levels of GPX, SOD, CAT, AOPP, MDA, N/N, and IMA in rats treated with dexmedetomidine before exposure to ionizing radiation.

Section snippets

Animals and groups

All methods were approved by the Ethical Committee of Laboratory Animal Research of Karadeniz Technical University (protocol no. 4-2013). Ten- to 12-week-old Sprague-Dawley male rats weighing 250-300 g were used in this study. The rats were divided into 4 groups. Group S was administered physiologic serum and were not irradiated (n = 7). Group SR was administered physiologic serum and radiation (n = 7). Group D100 was administered 100 μg/kg dexmedetomidine and radiation (n = 7). Group D200 was

Alterations in GPX levels

The GPX levels in plasma and hepatic, renal, lung, and thyroid tissues were significantly different between the 4 groups (all P < .005; Table). Changes in plasma and tissue GPX levels among various groups are shown in Figure 1A. In plasma, GPX levels dropped when rats were exposed to radiation, and these levels recovered in the presence of dexmedetomidine. The GPX level was significantly lower in group SR than in groups S (P = .038), D100 (P = .003), and D200 (P = .004). In hepatic tissue, GPX levels

Discussion

Consistent with previous studies [6], [7], we observed that ionizing radiation caused oxidative stress by increasing oxidative metabolites, such as AOPP, N/N, MDA, and IMA, and decreasing antioxidant defense mechanisms, including GPX, SOD, and CAT, in plasma and hepatic, renal, lung, and thyroid tissues. However, dexmedetomidine administration provided considerable protection from the oxidative stress caused by ionizing radiation. This is the first study investigating the protective effects of

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^☆: We declare that there is no conflict of interest.

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Original ContributionDexmedetomidine acts as an oxidative damage prophylactic in rats exposed to ionizing radiation☆

Highlights

Abstract

Study objective

Design

Setting

Interventions

Measurements

Main results

Conclusions

Introduction

Section snippets

Animals and groups

Alterations in GPX levels

Discussion

Life Sci

Ecotoxicol Environ Saf

Int J Radiat Oncol Biol Phys

J Clin Anesth

Nutrition

Br J Anaesth

Int J Surg

J Surg Res

Br J Anaesth

Modeling radiation-induced cell death: role of different levels of DNA damage clustering

Radiat Environ Biophys

Comparison of the effect of propofol and N-acetyl cysteine in preventing ischaemia-reperfusion injury

Eur J Anaesthesiol

Propofol and tourniquet induced ischaemia reperfusion injury in lower extremity operations

Eur J Anaesthesiol

Antioxidant approaches to management of ionizing irradiation injury

Antioxidants

Melatonin protects rat liver against irradiation-induced oxidative injury

J Radiat Res

Original Contribution
Dexmedetomidine acts as an oxidative damage prophylactic in rats exposed to ionizing radiation☆