ABSTRACT
Background: Even though with immense improvement and extensive understanding of pathophysiology of sepsis induced organ failure and affected population, it continues to put hundreds of people worldwide to eternal sleep due to lack of targeted therapy. Newer treatment modalities is the dire need of time. The present study was aimed to ascertain the adequacy of phosphodiesterases inhibitor - pentoxifylline (75mg/kg i.p) in endotoxin/LPS induced hepatotoxicity in BALB/c mice.Methods: The number of animals in each group was six. Endotoxin/lipopolysaccharides induced hepatotoxicity was reproduced in mice by giving lipopolysaccharide of serotype E. coli intraperitoneally. To ascertain the Preventive role, pentoxifylline was administered forehand LPS injection whereas therapeutic potential adjuged via post LPS delivering. The extent of liver damage was evaluated through serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with histopathological examination of liver tissue.Results: Results set forth that serum ALT, AST levels and histological alteration abated considerably (p ?0.05) both in animals subjected to pentoxifylline pre and post-treatment.Conclusions: Pentoxifylline set up promising results in endotoxin induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis induced liver failure.
ABSTRACT
Background: Sepsis is characterized by overwhelming surge of cytokines and oxidative stress to one of many factors, gram negative bacteria commonly implicated. Despite major expansion and elaboration of sepsis pathophysiology and therapeutic approach; death rate remains very high in septic patients due to multiple organ damage including hepatotoxicity. The present study was aimed to ascertain the adequacy of melatonin (10mg/kg i.p), and its comparability with dexamethasone (3mg/kg i.p), delivered separately and collectively in endotoxin induced hepatotoxicity.Methods: The number of animals in each group was six. Endotoxin/LPS induced hepatotoxicity was reproduced in mice by giving LPS of serotype E. coli intraperitoneally. Preventive role was questioned by giving the experimental agent half an hour prior to LPS injection whereas therapeutic potential of the experimental agent was searched out via post LPS delivering. The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with histopathological examination of liver tissue.Results: Melatonin was prosperous in aversion (Group 3) and curation (Group 4) of LPS invoked hepatotoxicity as evident by lessening of augmented ALT (?0.01) and AST (?0.01) along with restoration of pathological changes on liver sections (p?0.05). Dexamethasone given before (Group5) and after LPS (Group 6) significantly (p?0.05) attenuated LPS generated liver injury. Combination therapy with dexamethasone in conjunction with melatonin (Group 7) after LPS administration tapered LPS evoked hepatic dysfunction statistically considerably, however the result was comparable to single agent therapy.Conclusions: Melatonin set up promising results in endotoxin induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis induced liver failure. Combination therapies however generated no synergistic results.
ABSTRACT
Background: Serotonin (5-HT) is a biogenic amine that functions as a neurotransmitter of sensorimotor functions in the digestive tract. Te role of 5-HT agents in the modulation of lower gastrointestinal function. Selective serotonin reuptake inhibitors (SSRIs) are of potential benefit in functional gastrointestinal diseases although formal evidence is lacking. Apart from central effects, they may have peripheral. The present study was carried out to find out the possible effects of fluoxetine and paroxetine on gastrointestinal smooth muscles of rabbit as they cause severe nausea and vomiting initially.Methods: Experimental study design. Power lab (USA) for recording the contractions of ileal smooth muscle of rabbit in response to serotonin, fluoxetine and paroxetine.Results: The percent responses with serotonin, fluoxetine and paroxetine were 100, 10.53, and 4.75 percent respectively.Conclusions: SSRIs (fluoxetine and paroxetine) were unable to enhance the serotonergic transmission in vitro inturn decreases the qualitative response.