Cardiotoxic injury caused by chronic administration of microcystin-YR

长期服用微囊藻毒素-YR引起的心脏毒性损伤

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作者:D Suput, R Zorc-Pleskovic, D Petrovic, A Milutinović

Abstract

Microcystins are cyclic peptide toxins. Chronic intoxication with well-known members of the microcystin family--microcystins-LR--induces liver tumour formation, injury of kidney and heart. Despite worldwide distribution in the environment, the effects of microcystins-YR have not been studied extensively. The aim of the study was to evaluate whether microcystins-YR, in relatively low doses, have a toxic effect on cardiomyocytes of chronically treated rats. Male adult Wistar rats were treated every second day for 8 months with microcystins-YR (10 microg/kg i.p., N = 5). Control groups were treated either with vehicle (ethanol and methanol 4 : 1 v/v; N = 5) or with physiologic saline (N = 4). The heart sections of microcystin-YR-treated rats revealed decreased volume density of cardiac muscle tissue (microcystins- YR = 0.485 mm3/mm3 +/- 0.003; vehicle = 0.493 mm3/mm3 +/- 0.002; saline = 0.492 mm3/mm3 +/- 0.002) due to fibrous proliferation. A few lymphocyte infiltrates were observed. Most of cardiomyocytes were enlarged (microcystins-YR = 20.19 microm +/- 1.34, vehicle = 17.45 microm +/- 0.52, saline = 16.00 microm +/- 1.43), with enlarged and often bizarre-shaped nuclei and decreased myofibril volume fraction (microcystins- YR = 0.416 mm3/mm3 +/- 0.009; vehicle = 0.472 mm3/ mm3 +/- 0.009; saline = 0.479 mm3/mm3 +/- 0.010). No TUNEL-positive cells were found in the heart sections of rats in all groups. The results allow the conclusion that chronic exposure to low doses of microcystins-YR may cause atrophy and fibrosis of the heart muscle.

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