scholarly journals Suppression of Inflammation-Associated Kidney Damage Post-Transplant Using the New PrC-210 Free Radical Scavenger in Rats

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1054
Author(s):  
Torsten R. Goesch ◽  
Nancy A. Wilson ◽  
Weifeng Zeng ◽  
Bret M. Verhoven ◽  
Weixiong Zhong ◽  
...  

Allograft kidney transplantation, which triggers host cellular- and antibody-mediated rejection of the kidney, is a major contributor to kidney damage during transplant. Here, we asked whether PrC-210 would suppress damage seen in allograft kidney transplant. Brown Norway (BN) rat kidneys were perfused in situ (UW Solution) with or without added 30 mM PrC-210, and then immediately transplanted into Lewis (LEW) rats. 20 h later, the transplanted BN kidneys and LEW rat plasma were analyzed. Kidney histology, and kidney/serum levels of several inflammation-associated cytokines, were measured to assess mismatch-related kidney pathology, and PrC-210 protective efficacy. Twenty hours after the allograft transplants: (i) significant histologic kidney tubule damage and mononuclear inflammatory cell infiltration were seen in allograft kidneys; (ii) kidney function metrics (creatinine and BUN) were significantly elevated; (iii) significant changes in key cytokines, i.e., TIMP-1, TNF-alpha and MIP-3A/CCL20, and kidney activated caspase levels were seen. In PrC-210-treated kidneys and recipient rats, (i) kidney histologic damage (Banff Scores) and mononuclear infiltration were reduced to untreated background levels; (ii) creatinine and BUN were significantly reduced; and (iii) activated caspase and cytokine changes were significantly reduced, some to background. In conclusion, the results suggest that PrC-210 could provide broadly applicable organ protection for many allograft transplantation conditions; it could protect transplanted kidneys during and after all stages of the transplantation process—from organ donation, through transportation, re-implantation and the post-operative inflammation—to minimize acute and chronic rejection.

Author(s):  
Paulina Iwan ◽  
Jan Stepniak ◽  
Malgorzata Karbownik-Lewinska

Abstract. Iodine is essential for thyroid hormone synthesis. Under normal iodine supply, calculated physiological iodine concentration in the thyroid is approx. 9 mM. Either potassium iodide (KI) or potassium iodate (KIO3) are used in iodine prophylaxis. KI is confirmed as absolutely safe. KIO3 possesses chemical properties suggesting its potential toxicity. Melatonin (N-acetyl-5-methoxytryptamine) is an effective antioxidant and free radical scavenger. Study aims: to evaluate potential protective effects of melatonin against oxidative damage to membrane lipids (lipid peroxidation, LPO) induced by KI or KIO3 in porcine thyroid. Homogenates of twenty four (24) thyroids were incubated in presence of either KI or KIO3 without/with melatonin (5 mM). As melatonin was not effective against KI-induced LPO, in the next step only KIO3 was used. Homogenates were incubated in presence of KIO3 (200; 100; 50; 25; 20; 15; 10; 7.5; 5.0; 2.5; 1.25 mM) without/with melatonin or 17ß-estradiol. Five experiments were performed with different concentrations of melatonin (5.0; 2.5; 1.25; 1.0; 0.625 mM) and one with 17ß-estradiol (1.0 mM). Malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. KIO3 increased LPO with the strongest damaging effect (MDA + 4-HDA level: ≈1.28 nmol/mg protein, p < 0.05) revealed at concentrations of around 15 mM, thus corresponding to physiological iodine concentrations in the thyroid. Melatonin reduced LPO (MDA + 4-HDA levels: from ≈0.97 to ≈0,76 and from ≈0,64 to ≈0,49 nmol/mg protein, p < 0.05) induced by KIO3 at concentrations of 10 mM or 7.5 mM. Conclusion: Melatonin can reduce very strong oxidative damage to membrane lipids caused by KIO3 used in doses resulting in physiological iodine concentrations in the thyroid.


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.


2020 ◽  
Vol 10 (01) ◽  
pp. e104-e109
Author(s):  
Antonio Molina-Carballo ◽  
Antonio Emilio Jerez-Calero ◽  
Antonio Muñoz-Hoyos

AbstractMelatonin, produced in every cell that possesses mitochondria, acts as an endogenous free radical scavenger, and improves energetic metabolism and immune function, by complex molecular crosstalk with other intracellular compounds. There is greatly increasing evidence regarding beneficial effects of acute and chronic administration of high melatonin doses, in infectious, developmental, and degenerative pathologies, as an endothelial cell and every cell protectant.


Neonatology ◽  
2020 ◽  
pp. 1-8
Author(s):  
Satoshi Hamano Yamato ◽  
Shinji Nakamura ◽  
Yinmon Htun ◽  
Makoto Nakamura ◽  
Wataru Jinnai ◽  
...  

<b><i>Background:</i></b> Therapeutic hypothermia (TH) is a standard therapy for neonatal hypoxic-ischaemic encephalopathy. One potential additional therapy is the free radical scavenger edaravone (EV; 3-methyl-1-phenyl-2-pyrazolin-5-one). <b><i>Objectives and Methods:</i></b> This study aimed to compare the neuroprotective effects of edaravone plus therapeutic hypothermia (TH + EV) with those of TH alone after a hypoxic-ischaemic insult in the newborn piglet. Anaesthetized piglets were subjected to 40 min of hypoxia (3–5% inspired oxygen), and cerebral ischaemia was assessed using cerebral blood volume. Body temperature was maintained at 39.0 ± 0.5°C in the normothermia group (NT, <i>n</i> = 8) and at 33.5 ± 0.5°C (24 h after the insult) in the TH (<i>n</i> = 7) and TH + EV (3 mg/kg intravenous every 12 h for 3 days after the insult; <i>n</i> = 6) groups under mechanical ventilation. <b><i>Results:</i></b> Five days after the insult, the mean (standard deviation) neurological scores were 10.9 (5.7) in the NT group, 17.0 (0.4) in the TH group (<i>p</i> = 0.025 vs. NT), and 15.0 (3.9) in the TH + EV group. The histopathological score of the TH + EV group showed no significant improvement compared with that of the other groups. <b><i>Conclusion:</i></b> TH + EV had no additive neuroprotective effects after hypoxia-ischaemia in neurological and histopathological assessments.


1997 ◽  
Vol 82 (4) ◽  
pp. 1119-1125 ◽  
Author(s):  
G. S. Supinski ◽  
D. Stofan ◽  
R. Ciufo ◽  
A. Dimarco

Supinski, G. S., D. Stofan, R. Ciufo, and A. DiMarco. N-acetylcysteine administration alters the response to inspiratory loading in oxygen-supplemented rats. J. Appl. Physiol. 82(4): 1119–1125, 1997.—Based on recent studies, it has been suggested that free radicals are elaborated in the respiratory muscles during strenuous contractions and contribute to the development of muscle fatigue. If this theory is correct, then it should be possible to attenuate the development of diaphragm fatigue and/or delay the onset of respiratory failure during loaded breathing by administering a free radical scavenger. The purpose of the present experiment was, therefore, to examine the effect of N-acetylcysteine (NAC), a free radical scavenger and glutathione precursor, on the evolution of respiratory failure in decerebrate unanesthetized rats breathing against a large inspiratory resistive load. We compared the inspiratory volume and pressure generation over time in animals pretreated with either saline or NAC (150 mg/kg) and then loaded until respiratory arrest. After arrest, the diaphragm was excised, and samples were assayed for reduced (GSH) and oxidized glutathione. As a control, we also assessed respiratory function and glutathione concentrations in groups of nonloaded saline- and NAC-treated animals. We found that NAC-treated animals were able to tolerate loading better than the saline-treated group, maintaining higher inspiratory pressures and sustaining higher inspired volumes. Administration of NAC also increased the time that animals could tolerate loading before the development of respiratory arrest. In addition, although saline-treated loaded animals had significant reductions in diaphragmatic GSH levels compared with unloaded controls, the magnitude of this reduction was blunted by NAC administration (i.e., GSH averaged 965 ± 113, 568 ± 83, 907 ± 39, and 784 ± 61 nmol/g for unloaded-saline, loaded-saline, unloaded-NAC, and loaded-NAC groups, P< 0.05, with the value for the loaded-saline group lower than the values for the two unloaded groups; GSH for the loaded-NAC group was not different, however, from unloaded controls). These data demonstrate that administration of NAC, a free radical scavenger, slows the rate of development of respiratory failure during inspiratory resistive loading.


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