Shock/Sepsis/Trauma/Critical CareEffects of hydrogen-rich saline treatment on polymicrobial sepsis
Introduction
Despite recent advances in antibiotic therapy and supportive care, sepsis-induced multiple organ dysfunction syndrome (MODS) is the major cause of death in the intensive care unit [1]. Although the underlying pathophysiology is not well defined, overproduction of proinflammatory molecules such as cytokines, nitric oxide (NO), and reactive oxygen species (ROS) leads to tissue damage and organ dysfunction [2], [3], [4]. Thus, agents aiming to reduce these proinflammatory molecules may be used for the treatment of sepsis and the prevention of organ damage.
It has been well established that hydrogen gas (H2) can effectively reduce the organ damage induced by ischemia/reperfusion injury [5], [6], [7], [8], [9], [10]. The mechanisms underlying the protective effects of H2 may be attributed to its anti-inflammation and antioxidation properties [5], [6], [10]. Nevertheless, H2 application presents an issue with its safety and convenience, which enormously limits its clinical use.
Recently, hydrogen-rich saline (HRS), a newly developed H2-saturated physiological saline with more safety and convenience, has been proposed as a novel antioxidant that can selectively reduce the levels of toxic ROS such as hydroxyl radicals without affecting other signal ROS [11]. Numerous studies have suggested that HRS exerts its beneficial effects in diverse animal models of oxidative stress, including inflammatory and neurologic diseases [12], [13], [14], [15], [16]. However, the protective effects of HRS for polymicrobial sepsis have not been well documented.
Therefore, the present study aimed to test the hypothesis that HRS can improve organ dysfunction in a rat model of polymicrobial sepsis induced by cecal ligation and puncture (CLP).
Section snippets
Animal sepsis model
Adult male Sprague-Dawley rats weighing 350–410 g were purchased from Experimental Animal Central of Jinling Hospital. All animals were maintained under a 12-h light/dark cycle with constant temperature and access to food and water ad libitum. The study protocol was approved by the Ethics Committee of Jinling Hospital and the experiment was performed in accordance with the National Institutes of Health's Guidelines for the Care and Use of Laboratory Animals.
Rats were anesthetized with 2% sodium
HRS administration alleviated oxidative stress
As shown in Table 1, oxidant stress in lung tissue was evaluated by measuring pulmonary MDA levels 24 h after CLP. HRS administration significantly decreased pulmonary MDA levels (1.49 ± 0.11 nmol/mg protein) compared with the CLP group (1.78 ± 0.15 nmol/mg protein) (P < 0.05).
HRS administration improved antioxidant enzymatic activities
Antioxidant enzymatic activities were assessed by measuring pulmonary SOD levels 24 h after CLP. HRS administration significantly increased pulmonary SOD levels (117 ± 12 U/mg protein) compared with the CLP group (78 ± 9
Discussion
The major finding of the present study was that HRS administration improved organ dysfunction by downregulating oxidative stress, inhibiting proinflammatory cytokines, and reducing apoptosis in a rat model of polymicrobial sepsis. Although the improved organ dysfunction was observed at 24 h after CLP in the present study, HRS administration did not improve the 7-d survival rate.
Sepsis, which is typically followed by MODS, is the most common cause of death in the intensive care unit. The CLP
Conclusion
In summary, an intraperitoneal injection of HRS 5 mL/kg starting at 0, 6, and 18 h after CLP has been shown to exert potential protective effects for rats with polymicrobial sepsis via decreasing proinflammatory responses, oxidative stress, and apoptosis.
Acknowledgment
Supported by Jiangsu Six Talent Summit Foundation (Grant No. 2008093) and Jiangsu University Foundation (JLY2010052). Performed in Jinling Hospital.
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These two authors contributed equally to this work.