Pharmacological protection of NSAID- induced intestinal permeability in the rat: effect of tempo and metronidazole as potential free radical scavengers

1997 ◽  
Vol 16 (7) ◽  
pp. 345-349 ◽  
Author(s):  
Neal M Davies ◽  
Fakhreddin Jamali

Recently, NSAID-induced changes in both the structure and function of the distal intestine have been found to occur more frequently and with greater toxicological significance than previously thought. We have previously validated a suitable animal model to evaluate intestinal permeability changes using orally administered 51Cr- EDTA that correlates with intestinal ulceration. In this study we investigated the suitability of metronidazole and the nitroxide stable free radical scavenger (tempo) as protective agents against NSAID-induced intestinal per meability. Male Sprague-Dawley rats were dosed with two doses of metronidazole (50 mg/kg, 12 and 1 h pre-NSAID) or a single 100 mg/kg dose of tempo 1 h prior to NSAIDs. The urinary excretion of the orally administered marker 51Cr-EDTA was measured. Both tempo and metronidazole dramatically reduced indomethacin (20 mg/kg) and flur biprofen (10 mg/kg)-induced intestinal permeability. All the animals exposed to indomethacin alone died within 48-96 h and presented with histological evidence of drug- induced enteropathy, ulceration and frank peritonitis. Protection by tempo and metronidazole suggests that free radicals and/or bacteria may be important mediators in the pathogenesis of intestinal mucosal damage induced by NSAIDs. Nitric oxide donor compounds used concomi tantly with NSAIDs may protect gastrointestinal tract.

2010 ◽  
Vol 4 (05) ◽  
pp. 334-344
Author(s):  
Amany Sayed Maghraby ◽  
Manal Abdel-Aziz Hamed ◽  
Sanaa Ahmed Ali

Background: In this study, we evaluated the biochemical, immunological, histopathological and antischistosomal activities of Schistosoma mansoni or Fasciola gigantica worm homogenates mixed either with or without saponin that was extracted from Atriplex nummularia. Methodology: The immunization schedule was based on subcutaneous administration of two doses (50 μg /100 μl PBS) of each homogenate with time intervals of 15 days. After 15 days of the last homogenate inoculation, all mice were challenged with 100 Schistosoma mansoni cercariae and sacrificed after two months. Free radical scavengers and liver function enzymes were determined in mice liver. Worm counting and the histopathological picture of the liver were also done. Results: Immunization with Schistosoma or Fasciola worm homogenates, mixed either with or without saponin, recorded an amelioration of the free radical scavenger levels, liver function enzymes and reduction in worm burden, as well as improvement of the histological feature of the liver, the number and size of granuloma, evidence of increased immune reaction manifested by a lymphocytic cuff surrounding the granuloma, diminution of its fibrotic and collagen content, and destruction of Schistosoma ova. Conclusion: Fasciola or Schistosoma worm antigens mixed with or without saponin succeeded to eliminate the product of oxidative stress and assistance in immune-mediated destruction of eggs that ameliorate the histopathological picture of the liver cells and preserve its function.


2010 ◽  
Vol 112 (2) ◽  
pp. 432-439 ◽  
Author(s):  
Hee Kee Kim ◽  
Yan Ping Zhang ◽  
Young Seob Gwak ◽  
Salahadin Abdi

Background Paclitaxel is a widely used chemotherapeutic drug for breast and ovarian cancer. Unfortunately, it induces neuropathic pain, which is a dose-limiting side effect. Free radicals have been implicated in many neurodegenerative diseases. The current study tests the hypothesis that a free radical scavenger plays an important role in reducing chemotherapy-induced neuropathic pain. Methods Neuropathic pain was induced by intraperitoneal injection of paclitaxel (2 mg/kg) on four alternate days (days 0, 2, 4, and 6) in male Sprague-Dawley rats. Phenyl N-tert-butylnitrone (PBN), a free radical scavenger, was administered intraperitoneally as a single dose or multiple doses before or after injury. Mechanical allodynia was measured by using von Frey filaments. Results The administration of paclitaxel induced mechanical allodynia, which began to manifest on days 7-10, peaked within 2 weeks, and plateaued for at least 2 months after the first paclitaxel injection. A single injection or multiple intraperitoneal injections of PBN ameliorated paclitaxel-induced pain behaviors in a dose-dependent manner. Further, multiple administrations of PBN starting on day 7 through day 15 after the first injection of paclitaxel completely prevented the development of mechanical allodynia. However, an intraperitoneal administration of pbn for 8 days starting with the first paclitaxel injection did not prevent the development of pain behavior. Conclusions This study clearly shows that PBN alleviated mechanical allodynia induced by paclitaxel in rats. Furthermore, our data show that PBN given on days 7 through 15 after the first paclitaxel injection prevented the development of chemotherapy-induced neuropathic pain. This clearly has a clinical implication.


Author(s):  
A. Mathur ◽  
R.C. Russell ◽  
A.C. Roth ◽  
D. Wagahoff

Skeletal muscle is very sensitive to ischemia. A prolonged preoperative ischemic interval decreases the chances for successful replantation of an amputated limb. Recent experimental work has implicated toxic oxygen free radicals produced during reperfusion of ischemic tissue to be responsible for some of the observed deleterious cellular changes. Selected oxygen free radical scavengers have been used to increase skeletal muscle survival following total ischemia. This study examined the effect of systemic administration of a superoxide free radical scavenger, superoxide dismutase (SOD), and a hydroxyl radical scavenger, dimethylsulfoxide (DMSO) just prior to reperfusion, on the ultrastructure and function of ischemic rabbit anterior tibialis muscle.White male New Zealand rabbits were used for this study. The right hind limb of each rabbit was made ischemic by dissecting and clamping the femoral artery and vein proximal to the bifurcation of the profundus artery and vein. A penrose tourniquet was also placed around the knee. The animals were divided into groups subjected to either 5 or 8 hours of ischemia.


Cosmetics ◽  
2019 ◽  
Vol 6 (2) ◽  
pp. 27 ◽  
Author(s):  
Francesca Ferri ◽  
Fabio Olivieri ◽  
Roberto Cannataro ◽  
Maria Cristina Caroleo ◽  
Erika Cione

Phytomelatonin (PM) gained the greatest interest for its application in agriculture and its use to improve human health conditions. PM based supplement has been shown to possess antioxidant capabilities because it functions as a free radical scavenger. Reactive Oxygen Species (ROS), induced by both intrinsic (peroxide production) and extrinsic (UV-radiation) factors are biochemical mediators crucial in skin aging. Skin aging is also regulated by specific microRNAs (miRs). Herein we have shown the effect of PM free radical scavengers on the human keratinocyte cell line HaCat and on ROS formation induced by both extrinsic and intrinsic factors as well as their capability to positively modulate a member of the hsa-miR-29 family linked to aging. Our result highlights the regulatory role of PM for the keratinocytes homeostasis.


2004 ◽  
Vol 7 (4) ◽  
pp. 477-481 ◽  
Author(s):  
William Banz ◽  
Steve Hauck ◽  
Brian Gename ◽  
Todd Winters ◽  
Andrzej Bartke

2008 ◽  
Vol 63 (1-2) ◽  
pp. 66-68 ◽  
Author(s):  
Ning Li ◽  
Xian Li ◽  
Yi Zhang ◽  
Tao Wang ◽  
Wan Xiao

Flavonoids and organic acids were recommended in the literature as the main active constituents of Camptosorus sibiricus Rupr. Assay-guided fractionation led to the isolation of 9 flavonoids and 8 phenolic acids. All compounds were tested for DPPH scavenging activity, SOD-like and aldose reductase inhibition. Among them, compounds 1, 2, 3, 5, 6, 7, 8, 9, 11, 15 showed activities. The most active free radical scavenger and antioxidant was compound 8, while compound 1 exhibited strong inhibiting activity of aldose reductase. The structureactivity relation was dicussed briefly.


2019 ◽  
Vol 3 (2) ◽  
pp. 35
Author(s):  
Kartini Kartini ◽  
Azminah Azminah

In order to prepare standardized extract, optimization of extraction conditions of grape seed has been done. These conditions are type of menstrum (50, 70 and 96% of ethanolic solution), length of extraction (1, 2 and 4 hours) also method of evaporation (reduced pressure and opened air). Activity on free radical scavenger used as parameters to determine optimum conditions. Based on EC50 (concentration which scavenge 50% amount of free radical) can be concluded that optimum condition for extracting antioxidant active compound from grape seed are 70% ethanolic solution as menstrum, length of extraction 1 hour and evaporation on opened air use water bath.


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