Melatonin as Protection Against Radiation Injury: A Systematic Review.

INTRODUCTION: Radiation is widely used in the treatment of various cancers and in radiological imaging procedures. Ionizing radiation causes adverse effects, leading to decreased quality of life in patients, by releasing free radicals that cause oxidative stress and tissue damage. The sleep-hormone melatonin is a free radical scavenger, and induces several anti-oxidative enzymes. This review investigates the scientific literature on the protective effects of melatonin against exposure to ionizing radiation, and discusses the clinical potential of melatonin as prophylactic treatment against ionizing radiation damage. METHODS: A systematic literature search was performed and included experimental or clinical studies written in English that investigated the protective effects of melatonin against gamma or X-ray irradiation in vivo. Studies were excluded if patients were treated with chemotherapy concomitantly. RESULTS: 37 studies were included in the review. All were of experimental case-control design and employed animals. The studies demonstrated that exogenous melatonin reduced oxidative stress and inflammation in all investigated tissues. Furthermore, melatonin increased 30-day survival and protected against radiation enteritis. These protective effects were only documented when melatonin was administered prior to exposure to ionizing radiation. DISCUSSION: This review documents that melatonin effectively protects animals against injury to healthy tissues from ionizing radiation. However, no studies have been performed in humans. If clinical studies can document similar protective effects, melatonin could have a great potential to prevent side effects of radiotherapy for cancer, to protect against increased long-term cancer risk in radiological imaging procedures, and to protect from radiation due to nuclear incidents.

Pharmacokinetics of Alternative Administration Routes of Melatonin: A Systematic Review.

BACKGROUND: Melatonin is traditionally administered orally but has a poor and variable bioavailability. This study aims to present an overview of studies investigating the pharmacokinetics of alternative administration routes of melatonin. METHODS: A systematic literature search was performed and included experimental or clinical studies, investigating pharmacokinetics of alternative administration routes of melatonin in vivo. Alternative administration routes were defined as all administration routes except oral and intravenous. RESULTS: 10 studies were included in the review. Intranasal administration exhibited a quick absorption rate and high bioavailability. Transdermal administration displayed a variable absorption rate and possible deposition of melatonin in the skin. Oral transmucosal administration of melatonin exhibited a high plasma concentration compared to oral administration. Subcutaneous injection of melatonin displayed a rapid absorption rate compared to oral administration. CONCLUSION: Intranasal administration of melatonin has a large potential, and more research in humans is warranted. Transdermal application of melatonin has a possible use in a local application, due to slow absorption and deposition in the skin. Oral transmucosal administration may potentially be a clinically relevant due to avoiding first-pass metabolism. Subcutaneous injection of melatonin did not document any advantages compared to other administration routes.

A systematic review of peri-operative melatonin.

We systematically reviewed randomised controlled trials of peri-operative melatonin. We included 24 studies of 1794 participants that reported eight peri-operative outcomes: anxiety; analgesia; sleep quality; oxidative stress; emergence behaviour; anaesthetic requirements; steal induction; and safety. Compared with placebo, melatonin reduced the standardised mean difference (95% CI) pre-operative anxiety score by 0.88 (0.44-1.33) and postoperative pain score by 1.06 (0.23-1.88). The magnitude of effect was unreliable due to substantial statistical heterogeneity, with I(2) 87% and 94%, respectively. Qualitative reviews suggested the melatonin improved sleep quality and emergence behaviour, and might be capable of reducing oxidative stress and anaesthetic requirements.

Differentiation between benign and malignant colon tumors using fast dynamic gadolinium-enhanced MR colonography; a feasibility study.

BACKGROUND: Colorectal cancer will present itself as a bowel obstruction in 16-23% of all cases. However, not all obstructing tumors are malignant and the differentiation between a benign and a malignant tumor can be difficult. The purpose of our study was to determine whether fast dynamic gadolinium-enhanced MR imaging combined with MR colonography could be used to differentiate a benign from a malignant obstructing colon tumor. METHODS: Patients with benign colon tumor stenosis, based on diverticulitis, were asked to participate in the study. The same number of patients with verified colorectal cancer was included. Both groups had to be scheduled for surgery to be included. Two blinded observers analyzed the tumors on MR by placing a region of interest in the tumor and a series of parameters were evaluated, e.g. wash-in, wash-out and time-to-peak. RESULTS: 14 patients were included. The wash-in and wash-out rates were significantly different between the benign and malignant tumors, and a clear distinction between benign and malignant disease was therefore possible by looking only at the MR data. Furthermore, MR colography evaluating the rest of the colon past the stenosis was possible with all patients. CONCLUSION: The results showed the feasibility of using fast dynamic gadolinium-enhanced MR imaging to differentiate between benign and malignant colonic tumors. With a high intra-class correlation and significant differences found on independent segments of the tumor, the method appears to be reproducible. Furthermore, the potential is big in performing a full preoperative colon evaluation even in patients with obstructing cancer. TRIAL NUMBER: NCT00114829.

MR colonography with fecal tagging: barium vs. barium ferumoxsil.

RATIONALE AND OBJECTIVES: Both magnetic resonance (MR) and computed tomographic (CT) colonography are useful for colon examination. With sensitivities close to those for conventional colonoscopy (CC) for polyps, colonography has been proposed as an alternative to diagnostic CC. MR colonography (MRC) with fecal tagging may be a method of gaining further patient acceptance and widespread use, but the method has to be optimized. The aim of our study was to evaluate the quality of a new contrast agent mixture and to validate a new method for evaluating the tagging efficiency of contrast agents. MATERIALS AND METHODS: Twenty patients referred to CC underwent dark lumen MRC prior to the colonoscopy. Two groups of patients received two different oral contrast agents (barium sulfate and barium sulfate/ferumoxsil) as a laxative-free fecal tagging prior to the MRC. After MRC, the contrast agent was rated qualitatively (with the standard method using contrast-to-wall ratio) and subjectively (using a visual analog scale [VAS]) by three different blinded observers. RESULTS: Evaluated both qualitatively and subjectively, the tagging efficiency of barium sulfate/ferumoxsil was significantly better (P < .05) than barium sulfate alone. The VAS method for evaluating the tagging efficiency of contrast agents showed a high correlation (observer II, r = 0.91) to the standard method using contrast-to-wall ratio and also a high interclass correlation (observer II and III = 0.89/0.85). MRC found 1 of 22 (5%) polyps <6 mm, 2 of 3 (67%) polyps 6-10 mm, and 2 of 2 (100%) polyps >10 mm. CONCLUSION: MRC with fecal tagging using barium sulfate/ferumoxsil as contrast agent will give better overall assessment of the colon wall compared to barium sulfate alone. Furthermore, the VAS method of evaluating fecal tagging efficiency correlated with the standard method of calculating the contrast-to-wall ratio.