The Effects of S-Allyl Cysteıne on Inflammatory Cascade in Lipopolysaccharide Induced Rat Sepsis Model (original) (raw)
Related papers
Effect of N- acetyl- L-cysteine on sepsis in mice
European Journal of Pharmacology: Environmental Toxicology and Pharmacology, 1995
The effect of the antioxidant was studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture. significantly improved survival during the 6 days following sepsis induction and caused lower liver toxicity. This effect was not related to free radicals generated by xanthine oxidase which was significantly induced in liver after cecal ligation and puncture. A specific inhibitor of xanthine oxidase, allopurinol, significantly reduced this enzyme and reduced the early survival rate. The effect of was not related either to a reduction in tumor necrosis factor production or to a modulation of nitrites or to liver glutathione content. These results show that the induction of xanthine oxidase is not deleterious in this model of sepsis and suggest that works as a direct antioxidant and scavenger of free radicals generated from other sources.
Role of Free Radicals in Sepsis: Antioxidant Therapy
Current Pharmaceutical Design, 2005
Severe sepsis leading to shock is the principal cause of death in intensive care units. It is a systemic inflammatory response caused by excessive secretion of pro-inflammatory mediators, such as tumor necrosis factoralpha (TNFα) and reactive oxygen species (ROS), mainly induced by endotoxin (a major component of the Gramnegative bacterial outer membrane). Immune cells use ROS in order to support their functions and need adequate levels of antioxidant defenses to avoid harmful effects of an excessive ROS production. In addition, nitric oxide (NO) is thought to play a key role in the pathogenesis of sepsis and in the development of multiple organ failure. This article discusses the toxic effects of endotoxin, paying particular attention to cardiovascular damage. It continues by analysing the mechanism by which endotoxin is recognized by specific cells of the immune system, and the pathway leading to nuclear factor-κB (NF-κB) activation and pro-inflammatory gene transcription. In relation to this process, this review focuses on the involvement of reactive oxygen and nitrogen species. Finally, the protective role of antioxidants against homeostatic disturbances such as those caused by endotoxin toxicity, their potential clinical use and the effects on the redox state of the immune cells is discussed.
Critical Care, 2007
Hydrogen sulfide is produced endogenously by a variety of enzymes involved in cysteine metabolism. Clinical data indicate that endogenous levels of hydrogen sulfide are diminished in various forms of cardiovascular diseases. The aim of the current study was to investigate the effects of hydrogen sulfide supplementation on cardiac function during reperfusion in a clinically relevant experimental model of cardiopulmonary bypass. Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass. After 60 minutes of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n = 6), or the sodium sulfide infusion (1 mg/kg/hour, n = 6). Biventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters. Coronary and pulmonary blood flow, vasodilator responses to acetylcholine and sodiumnitroprusside and pulmonary function were also determined. Administration of sodium sulfide led to a significantly better recovery of left and right ventricular systolic function (P < 0.05) after 60 minutes of reperfusion. Coronary blood flow was also significantly higher in the sodium sulfide-treated group (P < 0.05). Sodium sulfide treatment improved coronary blood flow, and preserved the acetylcholine-induced increases in coronary and pulmonary blood (P < 0.05). Myocardial ATP levels were markedly improved in the sulfide-treated group. Thus, supplementation of sulfide improves the recovery of myocardial and endothelial function and energetic status after hypothermic cardiac arrest during cardiopulmonary bypass. These beneficial effects occurred without any detectable adverse hemodynamic or cardiovascular effects of sulfide at the dose used in the current study.
Heliyon
Sepsis is a major cause of death in intensive care units whose development is supported by an imbalance of oxidative stress and antioxidant. Superoxide dismutase (SOD) is a primer endogen antioxidant that prevents reactive oxygen species (ROS). Extensive studies on animals and humans have examined Cucumis melo L.C, a cantaloupe rich in SOD, and its combination with gliadin. The studies aimed to determine the effect of enteral administration of Cucumis melo L.C. gliadin (CME-gliadin) 28 days before inducing sepsis in rats. This experimental study aimed to compare four groups of male Wistar rats, including negative and positive control rats and those supplemented with SOD CME-gliadin 1 IU/day and SOD CME-gliadin 5 IU/day. All rats were given the same standard, except the supplementation for 28 days. Sepsis was induced by intraperitoneal injection of LPS 10 mg/kg. Enteral administration of SODgliadin extract of CME-gliadin for 28 days was used as antioxidant prophylaxis against oxidative stress due to sepsis. The results showed that enteral administration of CME-gliadin of 1 IU/day and 5 IU/day significantly increased SOD levels based on examination after 14 and 28 days. Also, it significantly decreased MDA (p < 0.001), TNF-α (p < 0.001), and lactate levels in rats induced by sepsis. However, the increase in lactate levels was above >1.64 mmol/l, indicating a high mortality rate. There was no significant difference in SOD, MDA, TNF-α, and Lactate levels between SOD 1 IU and SOD 5 IU. This descriptive data show that SOD 5 IU has a better result in MDA, TNF-α, and Lactate levels than SOD 1 IU.
Life Sciences, 2006
N-acetylcysteine (NAC) is an antioxidant and cytoprotective agent with scavenging action against reactive oxygen species and inhibitory effects on pro-inflammatory cytokines. In a previous study, we found that pretreatment with NAC attenuated organ dysfunction and damage, reduced the production of free radicals, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) following endotoxemia elicited by administration of lipopolysaccharide (LPS). In the present study, we tested the effects of post-treatment with NAC on the sepsis-induced change. Post-treatment imitates clinical therapeutic regimen with administration of drug after endotoxemia. Endotoxin shock was induced by intravenous injection of Klebsiella pneumoniae LPS (10 mg/kg) in conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were continuously monitored for 48 h after LPS administration. NAC was given 20 min after LPS. Measurements of biochemical substances were taken to reflect organ functions. Biochemical factors included blood urea nitrogen (BUN), creatinine (Cre), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transferase (GOT), alanine transferase (GPT), TNF-α, interleukin-6 (IL-6), and interleukin-10 (IL-10). LPS significantly increased blood BUN, Cre, LDH, CPK, GOT, GPT, TNF-α, IL-6, IL-10 levels and HR, and decreased MAP. Post-treatment with NAC diminished the decrease in MAP, increased the HR, and decreased the markers of organ injury (BUN, Cre, LDH, CPK, GOT, GPT) and inflammatory biomarkers (TNF-α, IL-6, IL-10) after LPS. We conclude that post-treatment with NAC suppresses the release of plasma TNF-α, IL-6, and IL-10 in endotoxin shock, and decreases the markers of organ injury. These beneficial effects protect against LPS-induced kidney, heart and liver damage in conscious rats. The beneficial effects may suggest a potential chemopreventive effect of this compound after sepsis.
Journal of advanced Biomedical and Pharmaceutical Sciences, 2020
Oxidative stress plays an important role in the development of sepsis and its associated serious consequence leading to multiple organ failure and death. Since the liver and the lungs are among the early affected organs responsible for the mortality in sepsis, we investigated the effect of Tempol, a superoxide dismutase mimetic agent, on lung and liver injuries in a cecal ligation and puncture (CLP)-induced sepsis. Septic animals were given Tempol either before or after CLP procedure. Sepsis outcomes were assessed mainly on the liver and lungs. Separate animal groups were employed for a survival study. CLP resulted in 0% survival, while Tempol pre-or post-treatment led to a 100 % and 40 % survival, respectively. Administration of Tempol resulted in a significant attenuation of sepsis-induced elevation of lipid peroxidation. In the lungs and liver tissues, Tempol resulted in a significant attenuation of elevated tumor necrosis factor-α and caspase-3. Histopathological examination of the lungs and liver confirmed the protective effects of Tempol on these organs. In conclusion: Tempol acts as both prophylactic and therapeutic agent in a rat sepsis model by lowering oxidative stress, inflammatory and apoptotic signals induced by sepsis and reducing lung and liver damage induced by sepsis.
Potential Antioxidant Multitherapy against Complications Occurring in Sepsis
Biomedicines
Septic shock currently represents one of the main causes of mortality in critical patient units with an increase in its incidence in recent years, and it is also associated with a high burden of morbidity in surviving patients. Within the pathogenesis of sepsis, oxidative stress plays an important role. The excessive formation of reactive oxygen species (ROS) leads to mitochondrial damage and vasomotor dysfunction that characterizes those patients who fall into septic shock. Currently, despite numerous studies carried out in patients with septic shock of different causes, effective therapies have not yet been developed to reduce the morbidity and mortality associated with this pathology. Despite the contribution of ROS in the pathophysiology of sepsis and septic shock, most studies performed in humans, with antioxidant monotherapies, have not resulted in promising data. Nevertheless, some interventions with compounds such as ascorbate, N-acetylcysteine, and selenium would have a pos...
Anti-inflammatory effects of LK-3, on LPS-induced sepsis in rats
The Chinese journal of physiology, 2008
Dextromethorphan (DM), an antitussive agent, has been shown to have anti-inflammatory and immunomodulatory effects in vitro. Thus, the aim of this study was to evaluate the effects of LK-3, an analog of DM, on sepsis induced by intravenous (i.v.) administration of lipopolysaccharide (LPS; 10 mg/ kg) in anesthetized Wistar rats. Results demonstrated that post-treatment with LK-3 (4 mg/kg, i.v.) significantly attenuated the deleterious hemodynamic changes (e.g., hypotension and bradycardia) in rats treated with LPS. Meanwhile, LK-3 (4 mg/kg) significantly inhibited the elevation of plasma tumor necrosis factor-alpha, as well as values of glutamate-oxalacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) caused by LPS. The induction of inducible NO synthase and the overproduction of NO and superoxide anions by LPS were also reduced by post-treatment of LK-3. Moreover, infiltration of neutrophils into the lungs and liver of rats 8 h after treatment with LPS was also redu...
Aqueous garlic extract protects against sepsis induced toxicity in pulmonary and ileal tissues
Medical Science and Discovery, 2016
Based on the potent antioxidant effects of aqueous garlic extract (AGE), the present study was designed to characterize the potential of AGE to modify blood coagulation parameters as well as and pulmonary and ileal injury in septic rats. Sepsis was induced using the caecal ligation and perforation (CLP) method. Material and Method: Twenty-four hours after sepsisinduction, rats were decapitated and trunk blood was collected for the measurement of platelet counts, fibrinogen, prothrombin time, activated partial thromboplastin time (APTT) and d-dimer levels. Then, pulmonary and ileal tissue samples were immediately obtained and stored at-70 °C for malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO) and superoxide dismutase (SOD) activity assays. Results: Sepsis was associated with a decrease in platelet count and fibrinogen and an increase in APTT and International normalized ratio. It also caused a significant decrease in GSH levels and SOD activity in both pulmonary and ileal tissue samples. On the other hand, AGE treatment in rats with CLP caused significantly augmented the level of these antioxidants. As a result of CLP induction increased MPO activity and MDA levels and decreased thromboplastic activity were reversed with AGE treatment. Conclusion: AGE treatment, through its antioxidant effects, protects against oxidative pulmonary and ileal injury and normalizes the impaired coagulation in sepsis.