Protective Effect of Melatonin on Infrarenal Aortic Occlusion: This Effect Is Related to Anti-inflammatory Effect and Antioxidant Effect

Abstract

Aortic cross-clamping is frequently exerted during surgery of the abdominal aorta (AA). Ischemia–reperfusion (IR) damage, which is observed in the surgery of AA, is a complex situation and is considered not only in lower extremities but also in remote tissues and organs like the lungs, kidneys, heart, and liver [1–6]. IR damage leads to important morbidity and mortality because of its systemic complications [7, 8]. Acute renal dysfunction, which is one of the most important complications following elective surgery of AA, is still a frequently seen condition (15– 22%), but acute kidney injury (AKI) is relatively rare (1.8– 4 %) [9, 10]. Infrarenal clamping of the aorta has been shown to decrease renal blood flow especially in patients who postoperatively developed renal failure [11–13]. This clamping procedure can cause vasoconstriction in renal arteries by forming turbulent flow in the aorta at the level of renal arteries [13]. The mechanisms underlying IR-induced organ damage are likely multifactorial and interdependent, involving hypoxia, inflammatory responses, and free radical damage [14–17]. Two of the most important factors in the pathophysiology of IR injury are reactive oxygen species (ROS) andmassive secretion of systemic inflammatorymediators, which especially increase in the reperfusion phase [18–20]. The endogenous antioxidants which are responsible for protecting against ROS during reperfusion have an important role in decreasing IR injury [18]. Melatonin, the main indolamine produced by the pineal gland, has been demonstrated to be an effective antioxidant and free radical scavenger [21–24]. Additionally, it has also shown an anti-inflammatory effect, which is suppression of proinflammatory cytokines like tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 [25– 30]. Melatonin has a small size and high lipophilicity; therefore, it crosses biological membranes easily and reaches all sections of the cell [22, 31, 32]. In this study, we aimed to investigate the anti-inflammatory, antioxidant, and protective effects of melatonin in IR damage developing in kidneys following infrarenal aortic occlusion–reperfusion in rat models and in preventing kidneys from this kind of damage.