Protective Effects of Antioxidant Peptide SS-31 Against Multiple Organ Dysfunctions During Endotoxemia
- PDF / 7,808,239 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 93 Downloads / 180 Views
Protective Effects of Antioxidant Peptide SS-31 Against Multiple Organ Dysfunctions During Endotoxemia Guoming Li,1 Jing Wu,2 Renqi Li,2 Dong Yuan,1 Yunxia Fan,1 Jianjun Yang,2 Muhuo Ji,2,3 and Sihai Zhu2,3
Abstract—Oxidative stress causes mitochondrial impairment, the failure of energy production, and consequent organ dysfunctions. The aim of the present study was to investigate the potential therapeutic effects of mitochondrial antioxidant SS-31 on sepsis-induced organ dysfunctions and to explore the possible mechanism. Sepsis was induced by cecal ligation and puncture. Immediately and at 5 h after the operation, SS-31 (5 mg/kg) or vehicle was administered intraperitoneally. The levels of organ dysfunctions, malondialdehyde, superoxide dismutase, proinflammatory cytokines, pulmonary wet-to-dry weight ratio, myeloperoxidase activity, histological scores, nuclear factor kappa B p65, inducible nitric oxide synthase, reactive oxygen species, adenosine triphosphate, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells were assessed at the indicated time points. The 7day survival rate was estimated by the Kaplan-Meier method. In the present study, SS-31 treatment significantly improved sepsis-induced organ dysfunctions as evidenced by decreased histological scores, increased arterial partial oxygen tension, and deceased serum alanine aminotransferase, urea nitrogen, and creatinine levels, which was accompanied by decreased levels of malondialdehyde, tumor necrosis factor-alpha, pulmonary myeloperoxidase activity, nuclear factor kappa B p65, inducible nitric oxide synthase, reactive oxygen species, and TUNEL-positive cells. In conclusion, our data suggested that the protective effects of SS-31 on sepsis-induced organ dysfunctions were associated with the inhibition of proinflammatory cytokines, oxidative stress, and apoptosis. KEY WORDS: sepsis; mitochondria; inflammation; oxidative stress; apoptosis.
INTRODUCTION Despite increased understanding of the complex pathophysiology of sepsis, it remains one of the major causes of morbidity and mortality in the intensive care units [1–4]. Sepsis represents an exaggerated inflammatory response and oxidative stress to infection that can progress to multiorgan dysfunction syndromes (MODS), which is characterized by a massive deregulated inflammatory response, overproduction of reactive oxygen species (ROS), Guoming Li and Jing Wu contributed equally to this work. 1
Department of Anesthesiology and Intensive Care, Jintan Hospital, Jiangsu University, Changzhou, China 2 Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan, Road, Nanjing, 210002, China 3 To whom correspondence should be addressed at Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan, Road, Nanjing, 210002, China. Emails: [email protected]; [email protected]
and reactive nitrogen species (RNS) in the circulation and the affected organs [4–6]. However, current thera
Data Loading...
