Biomedical subjects

Bojan Sedmak

Publications and source records attributed to Bojan Sedmak.

6 recordsLinked to original sources

PubMed2006

Microcystins induce morphological and physiological changes in selected representative phytoplanktons.

Dissolved microcystins (MCs) are regularly present in water dominated by microcystin-producing, bloom-forming cyanobacteria. In vitro experiments with environmentally feasible concentrations (5 x 10(-7) M) of the three most common microcystins, MC-LR, MC-RR, and MC-YR, revealed that they influence the metabolism of different representative phytoplanktons. At light intensities that are close to the cyanobacterial bloom environment (50 micromol m(-2) s(-1)), they produce morphological and physiological changes in both microcystin-producing and -nonproducing Microcystis aeruginosa strains and also have similar effects on the green alga Scenedesmus quadricauda that is frequently present in cyanobacterial blooms. All three microcystin variants tested induce cell aggregation, increase in cell volume, and overproduction of photosynthetic pigments. All three effects appear to be related to each other but are not necessarily caused by the same mechanism. The biological activity of microcystins toward the light-harvesting complex of photobionts can be interpreted as a signal announcing the worsening of light conditions due to the massive proliferation of cyanobacteria. Although the function of microcystins is still unknown, it is evident that they have numerous effects on phytoplankton in nature. These effects depend on the individual organism as well as on the various intracellular and extracellular signaling pathways. The fact that dissolved microcystins also influence the physiology of microcystin-producing cyanobacteria leads us to the conclusion that the role of microcystins in the producing cells differs from the role in the water environment.

Fluorescence↗

PubMed2005

Microcystins induce morphological and physiological changes in selected representative phytoplanktons.

Dissolved microcystins (MC) are regularly present in water dominated by microcystin-producing, bloom-forming cyanobacteria. In vitro experiments with environmentally feasible concentrations (5 x 10(-7) M) of the three most common microcystins, MC-LR, -RR, and -YR, revealed that they influence the metabolism of different representative phytoplanktons. At light intensities close to the cyanobacterial bloom environment (50 mumol m(-2) s(-1)), they produce morphological and physiological changes in both microcystin-producing and nonproducing Microcystis aeruginosa strains, and also have similar effects on the green alga Scenedesmus quadricauda that is frequently present in cyanobacterial blooms. All three microcystin variants tested induce cell aggregation, increase in cell volume, and overproduction of photosynthetic pigments. All three effects appear to be related to each other, but are not necessarily caused by the same mechanism. The biological activity of microcystins toward the light-harvesting complex of photobionts can be interpreted as a signal announcing the worsening of light conditions due to the massive proliferation of cyanobacteria. Although the function of microcystins is still unknown, it is evident that they have numerous effects on phytoplankton organisms in nature. These effects depend on the individual organism as well as on the various intracellular and extracellular signaling pathways. The fact that dissolved microcystins also influence the physiology of microcystin-producing cyanobacteria leads us to the conclusion that the role of microcystins in the producing cells differs from their role in the water environment.

Eutrophication↗

PubMed2004

Seco[D-Asp3]microcystin-RR and [D-Asp3,D-Glu(OMe)6]microcystin-RR, two new microcystins from a toxic water bloom of the cyanobacterium planktothrixrubescens.

Two novel microcystins, seco[d-Asp(3)]microcystin-RR (1) and [d-Asp(3),d-Glu(OMe)(6)]-microcystin-RR (2), along with the known [d-Asp(3)]microcystin-RR (3), were isolated from a Planktothrix rubescens toxic bloom collected in Lake Bled, Slovenia. The structures were deduced using one- and two-dimensional NMR techniques, ESIMS/CID/MS analysis, and Marfey's method for determining the amino acids' absolute stereochemistry. Compounds 1 and 3 exhibit weak PP1 inhibitory activity. The NMR data of compound 3 are reported here for the first time.

Amino Acid Sequence↗

PubMed2003

Microcystin-LR induces oxidative DNA damage in human hepatoma cell line HepG2.

Microcystins are naturally occurring hepatotoxins produced by strains of Microcystis aeruginosa. They are involved in promoting primary liver tumours and a previous study showed that they might also be tumour initiators. In this study we demonstrate that microcystin-LR (MCLR) at doses that were not cytotoxic (0.01-1 microg/ml), induced dose and time dependent DNA strand breaks in human hepatoma cell line HepG2. These DNA strand breaks were transient, reaching a maximum level after 4h of exposure and declining with further exposure. In the presence of the DNA repair inhibitors cytosine arabinoside (AraC) and hydroxyurea (HU), together with MCLR, DNA strand breaks accumulated after prolonged exposure. These results suggest that DNA strand breaks are intermediates, produced during the cellular repair of MCLR induced DNA damage. Digestion of DNA with purified, oxidative DNA damage specific enyzmes, endonuclease III (Endo III) and formamidopyrimidine-DNA glycosylase (Fpg) markedly increased DNA strand breaks in MCLR treated cells, providing evidence that a substantial portion of the MCLR induced DNA strand breaks originate from excision of oxidative DNA adducts. A hydroxyl radical scavenger (DMSO) significantly reduced MCLR induced DNA damage. From these results we conclude that MCLR induces formation of reactive oxygen species that cause DNA damage, and that MCLR may act as an initiator of liver cancer.

Bacterial Toxins↗

PubMed2003

Nephrotoxic effects of chronic administration of microcystins -LR and -YR.

Acute intoxication with MC-LR induces cytoskeletal alterations, apoptosis and necrosis of hepatocytes resulting in intrahepatic hemorrhage. Preliminary results have shown that chronic treatment of rats with intraperitoneal injections of sublethal doses of microcystins MC-LR and MC-YR could induce not only liver, but also kidney injuries. We aimed to investigate whether the induction of the cytoskeletal changes, apoptosis and necrosis could be the mechanisms involved in the injury of kidney cells in the chronic model of microcystin intoxication. Experimental rats were receiving intraperitoneal injections of MC-LR (10 microg/kg) or MC-YR (10 microg/kg) every second day for 8 months, while control rats were receiving only the vehicle. The histopathological investigation revealed collapsed glomeruli with thickened basement membranes and dilated tubuli filled with eosinophilic casts. Rhodamine-phalloidin labeling showed cytoplasmic aggregation and accumulation of fibrilar actin filaments within the epithelial tubular cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) showed increased number of TUNEL-positive cells in the kidney cortex and medulla. The pathological changes induced by MC-LR appeared more severe than those induced by MC-YR. The results support the view that at the cellular level, the mechanisms that underly the chronic nephrotoxicity are similar to the mechanisms of the acute hepatotoxicity of microcystins.

Analysis of Variance↗

PubMed2002

Renal injuries induced by chronic intoxication with microcystins.

The microcystins (MCs) LR and YR are hepatotoxins produced by some species of freshwater cyanobacteria. Only a few reports on the acute nephrotoxicity of MCs have been published to date. Here we investigate the effects on rat kidneys of chronic administration of relatively low doses of MC LR and MC YR. Male Wistar rats were injected every second day for 8 months with MC LR (10 microg/kg i.p., n=5) and MC YR (10 microg/kg i.p., n=5). The control group was treated with vehicle, a mixture containing 0.8 % ethanol and 0.2 % methanol in 0.9 % saline (3.7 ml/kg i.p., n=5). We found that MCs could induce damage to the kidney cortex and medulla. The lesions mainly consisted of damaged and dilated tubuli filled with homogenous eosinophil material. We conclude that long-term exposure to relatively low doses of MCs poses a considerable risk for kidney injury.

Animals↗