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Background: Doxorubicin, an effective anticancer drug used to treat multiple solid tumours and childhood malignancies since many decades but its cardiac adverse effects limits its use in full therapeutic dose. The mechanism involved in cardiotoxicity is apoptosis of cardiomyocytes due to reactive oxidative stress. The study was conducted to compare the cardioprotective effects of carvedilol and ?-Tocopherol and to detect myocardial injury at early stage.Methods: Cardiotoxicity was produced in a group of rabbits by single intravenous injection of doxorubicin; control group was treated with normal saline only. Third and fourth groups were pretreated with carvedilol 30 mg/kg bodyweight and ?-Tocopherol 200 mg/kg bodyweight respectively for ten days before injection of doxorubicin.Results: Doxorubicin produced marked cardiotoxicity represented by raised levels of serum biomarkers (cTnI, LDH and CK-MB) and severe necrosis of cardiomyocytes on microscopic examination. Carvedilol and ?-tocopherol pretreatment resulted in decreased serum levels of biomarkers and improved the histological picture of heart tissue.Conclusions: The outcome of doxorubicin chemotherapy can be made successful with the concurrent use of carvedilol or ?-tocopherol. Although carvedilol has more pronounced cardioprotective effects perhaps due to its antioxidant activity in addition to antiapoptotic, antiproliferative and anti-inflammatory effects. Furthermore the quantitative cTnI estimation for detection of cardiotoxicity at early stage can lead to significant economic impact in management of cancer.
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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.
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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.
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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.
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Background: Major depression is the most frequent disorder occurring in 16% of the population worldwide. In the middle of the 20th century, the discovery of selective serotonin (5-HT) reuptake inhibitors acted as a miracle in the antidepressant therapy. We explored the acute effects of fl uoxetine and possible mechanism underlying the contractile effects of fl uoxetine on isolated ileal smooth muscles of rabbit in vitro. Methods: Effects of increasing concentrations of acetylcholine (Ach), 5-HT and fl uoxetine were studied on isolated ileal tissue of the rabbit in vitro by constructing cumulative concentration response curves. The ileal smooth muscle contractions were recorded on power lab (USA). Results: Ach, 5-HT and fluoxetine, produced a concentration-dependent reversible contraction of isolated ileal muscle of rabbit. The mean ± standard error of the mean of maximum amplitudes of contraction with Ach, 5-HT and fl uoxetine, were 24.8±1.22 mm, 44±0.527 mm and 2.6±1.16 mm, respectively. Fluoxetine shifted the concentration-response curve right and downwards. Conclusion: Our study has indicated that fl uoxetine on isolated ileal intestinal smooth muscle decrease the motility and this decrease in motility is possibly due to the inability of fl uoxetine in vitro to enhance the serotonergic transmission and also because of the interaction of these agents with some of the other receptors, present in the intestinal smooth muscles.
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Background: We explored the acute effects of insulin and one possible mechanism underlying the acute contractile effects of insulin on isolated tracheal smooth muscle of guinea pig in vitro. Methods: Effects of increasing concentrations of histamine (10−7-10−3 M), insulin (10−7-10−3 M), insulin pretreated with a fixed concentration of indomethacin (10−6 M) were studied on isolated tracheal tissue of guinea pig in vitro by constructing cumulative concentration response curves. The tracheal smooth muscle contractions were recorded with transducer on four channel oscillograph. Results: Histamine and insulin produced a concentration-dependent reversible contraction of isolated tracheal muscle of guinea pig. The mean±standard error of the mean of maximum amplitudes of contraction with histamine, insulin and insulin pretreated with indomethacin were 92.5±1.20 mm, 35±1.13 mm and 14.55±0.62 mm respectively. Indomethacin shifted the concentration-response curve of insulin to the right and downwards. Conclusions: Insulin has acute contractile effects on guinea pig airways, which were significantly inhibited by prostaglandin synthesis inhibitor indomethacin confirming the involvement of contractile prostaglandins in insulin-induced airway hyper-responsiveness.