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Pharmacological doses of melatonin reduce the glycosaminoglycan level within the infarcted heart scar

100%

Drobnik J. , Slotwinska D. , Olczak S. , Tosik D. , Pieniazek A. , Matczak K. , Koceva-Chyla A. , Szczepanowska A.

nr 1

The aim of the study was to define the effect of pharmacological doses of melatonin, an agent known to be a scavenger of reactive oxygen species, on the extracellular matrix composition (glycosaminoglycans and collagen) in the infarcted heart scar. Rats were administered with melatonin at doses of 300 µg/100 g b.w. or 3 mg/100 g b.w. once daily (between 5:00 and 6:00 in the afternoon) or with 1.5 mg/100 g b.w. twice daily (between 8:00 and 9:00 in the morning and additionally between 5:00 and 6:00 in the afternoon). The levels of collagen, glycosaminoglycans (GAG) and some oxidative stress markers (lipid oxidation, the content of sulphydryl groups in proteins and glutathione) were evaluated. In the second part of the experiment, cells were isolated from the scar, identified as myofibroblasts, cultured and treated with melatonin at concentrations ranging from 10-7M to 10-10M. The pineal indoleamine was seen to reduce the GAG content of the scar, while the collagen content of the scar remained unchanged. A 10-7M concentration of melatonin caused an increase in the GAG level in the myofibroblast cultures, while lower concentrations (10-8M-10-10M) of pineal indoleamine were not effective. Melatonin decreased lipid oxidation and increased the sulphydryl groups of total proteins and glutathione, which suggests its antioxidative activity in the applied doses. The present study shows that pharmacological doses of melatonin reduce the GAG level in an infarcted heart scar. Since the mechanism of GAG content reduction cannot be explained by direct action of the pineal indoleamine on myofibroblasts in the myocardial infarction scar, we hypothesise that changes in GAG content could be indirectly induced by melatonin, that is caused by changes in regulatory systems or reduction of the inflammatory reaction in the area of the infarction. In addition, this paper shows that long-term treatment with melatonin of rats affected by myocardial infarction may reduce oxidative stress in the infarction area.

Experimental hypothyroidism increases content of collagen and glycosaminoglycans in the heart

100%

Drobnik J. , Ciosek J. , Slotwinska D. , Stempniak B. , Zukowska D. , Marczynski A. , Tosik D. , Bartel H. , Dabrowski R. , Szczepanowska A.

2009

tom 60

nr 3

57-62

The connective tissue matrix of the heart remains under regulatory influence of the thyroid hormones. Some conflicting data describe the connective tissue changes in subjects with thyroid gland disorders. The aim of the study was to assess the changes of the connective tissue accumulation in the heart of rats in the state of hypothyroidism and to answer the question whether TSH is involved in mechanism of the observed phenomena. Hypothyroidism in rats was induced by methylotiouracil treatment or by thyreoidectomy. The thyroid hormones [freeT3 (fT3), freeT4 (fT4)] and pituitary TSH were measured in plasma with radioimmunological method. The glycosaminoglycans (GAG) and total collagen were measured in heart muscle of both left and right ventricles. Cells from the rat’s heart were isolated and cultured. The cells were identified as myofibroblasts by electron microscopy method. The effects of TSH in concentrations ranging from 0.002 to 20 mIU/ml, on connective tissue accumulation in heart myofibroblasts cultures were tested. The primary hypothyroidism was developed both in groups with thyroidectomy and with methylthiouracil. The levels of fT3 and fT4 both in rats with thyreoidectomy and animals treated with methylthiouracil were decreased and TSH level in these two experimental groups was elevated. In the heart of the rats with experimental hypothyroidism increased content of both GAG and collagen was found. Myofibroblast number in culture was increased by TSH. Regardless of the method of its induction, hypothyroidism increased collagen and GAG contents in the heart. TSH is not involved in regulation of collagen and glycosaminoglycans accumulation in the heart of rats affected with primary hypothyroidism.

Melatonin-induced glycosaminoglycans augmentation in myocardium remote to infarction

100%

Drobnik J. , Tosik D. , Piera L. , Szczepanowska A. , Olczak S. , Zielinska A. , Liberski P. P. , Ciosek J.

tom 64

nr 6