TY - JOUR
T1 - Pharmacological utility of melatonin in the treatment of septic shock
T2 - Experimental and clinical evidence
AU - Escames, Germaine
AU - Acuña-Castroviejo, Darío
AU - López, Luis Carlos
AU - Tan, Dun-Xian
AU - Maldonado, Maria Dolores
AU - Sánchez-Hidalgo, Marina
AU - León, Josefa
AU - Reiter, Russel J.
PY - 2006/9
Y1 - 2006/9
N2 - Sepsis is a major cause of mortality in critically ill patients and develops as a result of the host response to infection. In recent years, important advances have been made in understanding the pathophysiology and treatment of sepsis. Mitochondria play a central role in the intracellular events associated with inflammation and septic shock. One of the current hypotheses for the molecular mechanisms of sepsis is that the enhanced nitric oxide (NO) production by mitochondrial nitric oxide synthase (mtNOS) leads to excessive peroxynitrite (ONOO-) production and protein nitration, impairing mitochondrial function. Despite the advances in understanding of its pathophysiology, therapy for septic shock remains largely symptomatic and supportive. Melatonin has well documented protective effects against the symptoms of severe sepsis/shock in both animals and in humans; its use for this condition significantly improves survival. Melatonin administration counteracts mtNOS induction and respiratory chain failure, restores cellular and mitochondrial redox status, and reduces proinflammatory cytokines. Melatonin clearly prevents multiple organ failure, circulatory failure, and mitochondrial damage in experimental sepsis, and reduces lipid peroxidation, indices of inflammation and mortality in septic human newborns. Considering these effects of melatonin and its virtual absence of toxicity, the use of melatonin (along with conventional therapy) to preserve mitochondrial bioenergetics as well as to limit inflammatory responses and oxidative damage should be seriously considered as a treatment option in both septic newborn and adult patients. This review summarizes the data that provides a rationale for using melatonin in septic shock patients.
AB - Sepsis is a major cause of mortality in critically ill patients and develops as a result of the host response to infection. In recent years, important advances have been made in understanding the pathophysiology and treatment of sepsis. Mitochondria play a central role in the intracellular events associated with inflammation and septic shock. One of the current hypotheses for the molecular mechanisms of sepsis is that the enhanced nitric oxide (NO) production by mitochondrial nitric oxide synthase (mtNOS) leads to excessive peroxynitrite (ONOO-) production and protein nitration, impairing mitochondrial function. Despite the advances in understanding of its pathophysiology, therapy for septic shock remains largely symptomatic and supportive. Melatonin has well documented protective effects against the symptoms of severe sepsis/shock in both animals and in humans; its use for this condition significantly improves survival. Melatonin administration counteracts mtNOS induction and respiratory chain failure, restores cellular and mitochondrial redox status, and reduces proinflammatory cytokines. Melatonin clearly prevents multiple organ failure, circulatory failure, and mitochondrial damage in experimental sepsis, and reduces lipid peroxidation, indices of inflammation and mortality in septic human newborns. Considering these effects of melatonin and its virtual absence of toxicity, the use of melatonin (along with conventional therapy) to preserve mitochondrial bioenergetics as well as to limit inflammatory responses and oxidative damage should be seriously considered as a treatment option in both septic newborn and adult patients. This review summarizes the data that provides a rationale for using melatonin in septic shock patients.
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U2 - 10.1211/jpp.58.9.0001
DO - 10.1211/jpp.58.9.0001
M3 - Review article
C2 - 16945173
AN - SCOPUS:33748356926
SN - 0022-3573
VL - 58
SP - 1153
EP - 1165
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
IS - 9
ER -