Rofecoxib Increases Susceptibility of Human LDL and Membrane Lipids to Oxidative Damage: A Mechanism of Cardiotoxicity

2006 ◽  
Vol 47 (Supplement 1) ◽  
pp. S7-S14 ◽  
Author(s):  
R. Preston Mason ◽  
Mary F. Walter ◽  
Hyesun P. McNulty ◽  
Samuel F. Lockwood ◽  
Jungsoo Byun ◽  
...  
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.


2013 ◽  
Vol 6 (1) ◽  
pp. 10 ◽  
Author(s):  
Magdalena Milczarek ◽  
Jan Stepniak ◽  
Andrzej Lewinski ◽  
Malgorzata Karbownik-Lewinska

1986 ◽  
Vol 20 (2) ◽  
pp. 140-147 ◽  
Author(s):  
J. M. C. Gutteridge ◽  
L. F. Taffs ◽  
C. M. Hawkey ◽  
C. Rice-Evans

Captive Callitrichids frequently suffer a fatal wasting disease, wasting marmoset syndrome (WMS), of unexplained cause. This paper describes studies on the erythrocytes from animals in a breeding colony of tamarins ( Saguinus labiatus), in which deaths from anaemia and wasting were occurring, to seek evidence for biochemical changes which could lead to oxidative damage and premature cell lysis. In only one animal of 33 studied did the red blood cell lipids show an increased susceptibility to oxidative damage. This animal, with some degree of certainty, could be diagnosed as having WMS. It was concluded that evidence for a primary deficiency of antioxidants as a cause of unexplained deaths, or WMS, in the colony could not at present be substantiated.


Toxics ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 89
Author(s):  
Paulina Iwan ◽  
Jan Stepniak ◽  
Malgorzata Karbownik-Lewinska

Iodine deficiency is the main environmental factor leading to thyroid cancer. At the same time iodine excess may also contribute to thyroid cancer. Potassium iodate (KIO3), which is broadly used in salt iodization program, may increase oxidative damage to membrane lipids (lipid peroxidation, LPO) under experimental conditions, with the strongest damaging effect at KIO3 concentration of ~10 mM (corresponding to physiological iodine concentration in the thyroid). Melatonin and indole-3-propionic acid (IPA) are effective antioxidative indoles, each of which protects against KIO3-induced LPO in the thyroid. The study aims to check if melatonin used together with IPA (in their highest achievable in vitro concentrations) reveals stronger protective effects against KIO3-induced LPO in porcine thyroid homogenates than each of these antioxidants used separately. Homogenates were incubated in the presence of KIO3 (200; 100; 50; 25; 20; 15; 10; 7.5; 5.0; 2.5; 1.25; 0.0 mM) without/with melatonin (5 mM) or without/with IPA (10 mM) or without/with melatonin + IPA, and then, to further clarify the narrow range of KIO3 concentrations, against which melatonin + IPA reveal cumulative protective effects, the following KIO3 concentrations were used: 20; 18.75; 17.5; 16.25; 15; 13.75; 12.5; 11.25; 10; 8.75; 7.5; 0.0 mM. Malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. Protective effects of melatonin + IPA were stronger than those revealed by each antioxidant used separately, but only when LPO was induced by KIO3 in concentrations from 18.75 mM to 8.75 mM, corresponding to physiological iodine concentration in the thyroid. In conclusion, melatonin and indole-3-propionic acid exert cumulative protective effects against oxidative damage caused by KIO3, when this prooxidant is used in concentrations close to physiological iodine concentrations in the thyroid. Therefore, the simultaneous administration of these two indoles should be considered to prevent more effectively oxidative damage (and thereby thyroid cancer formation) caused by iodine compounds applied in iodine prophylaxis.


Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 592
Author(s):  
Paulina Iwan ◽  
Jan Stepniak ◽  
Malgorzata Karbownik-Lewinska

Not only iodine deficiency, but also its excess may contribute to thyroid cancer. Potassium iodate (KIO3), which is broadly used in the salt iodization program, can increase oxidative damage to membrane lipids (lipid peroxidation, LPO) under experimental conditions, with the strongest damaging effect at KIO3 concentration of ~10 mM (corresponding to physiological iodine concentration in the thyroid). Melatonin is an effective antioxidant, which protects against KIO3-induced LPO in the thyroid. This study aimed to compare the protective effects of melatonin, used in the highest achievable in vitro concentration, against KIO3-induced oxidative damage to membrane lipids in various porcine tissues (thyroid, ovary, liver, kidney, brain, spleen, and small intestine). Homogenates were incubated in the presence of KIO3 (20; 15; 10; 7.5; 5.0; 0.0 mM) without/with melatonin (5 mM). The malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. KIO3 increased the LPO in all examined tissues; in the thyroid, the damaging effect of KIO3 (10; and 7.5 mM) was lower than in other tissues and was not observed for the lowest concentration of 5 mM. Melatonin reduced LPO induced by KIO3 (10, 7.5, and 5 mM) in all tissues, and in the thyroid it was also protective against as high a concentration of KIO3 as 15 mM; the LPO level resulting from KIO3 + melatonin treatment was lower in the thyroid than in other tissues. In conclusion, the thyroid is less sensitive tothe pro-oxidative effects of KIO3 compared to other tissues. The strongest protective effect of melatonin was observed in the thyroid, but beneficial effects were significant also in other tissues. Melatonin should be considered to avoid the potential damaging effects of iodine compounds applied in iodine prophylaxis.


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