PMID- 14559079 OWN - NLM STAT- MEDLINE DCOM- 20031215 LR - 20201208 IS - 0041-0101 (Print) IS - 0041-0101 (Linking) VI - 42 IP - 3 DP - 2003 Sep TI - Nephrotoxic effects of chronic administration of microcystins -LR and -YR. PG - 281-8 AB - 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. FAU - Milutinovic, Aleksandra AU - Milutinovic A AD - Institute of Pathophysiology, Medical Faculty of Ljubljana, University of Ljubljana, Zaloska 4, 1000 Ljubljana, Slovenia. FAU - Zivin, Marko AU - Zivin M FAU - Zorc-Pleskovic, Ruda AU - Zorc-Pleskovic R FAU - Sedmak, Bojan AU - Sedmak B FAU - Suput, Dusan AU - Suput D LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Toxicon JT - Toxicon : official journal of the International Society on Toxinology JID - 1307333 RN - 0 (Bacterial Toxins) RN - 0 (Cytoskeletal Proteins) RN - 0 (Enzyme Inhibitors) RN - 0 (Marine Toxins) RN - 0 (Microcystins) RN - 0 (Peptides, Cyclic) RN - 101064-48-6 (microcystin YR) RN - EQ8332842Y (cyanoginosin LR) SB - IM MH - Analysis of Variance MH - Animals MH - Apoptosis/drug effects MH - Bacterial Toxins/*toxicity MH - Cytoskeletal Proteins/drug effects MH - Cytoskeleton/*drug effects/pathology MH - Enzyme Inhibitors/toxicity MH - Kidney/*drug effects/pathology MH - Male MH - Marine Toxins MH - Microcystins MH - Necrosis MH - Peptides, Cyclic/*toxicity MH - Rats MH - Rats, Wistar MH - Renal Circulation/drug effects MH - Toxicity Tests, Chronic EDAT- 2003/10/16 05:00 MHDA- 2003/12/16 05:00 CRDT- 2003/10/16 05:00 PHST- 2003/10/16 05:00 [pubmed] PHST- 2003/12/16 05:00 [medline] PHST- 2003/10/16 05:00 [entrez] AID - S0041010103001430 [pii] AID - 10.1016/s0041-0101(03)00143-0 [doi] PST - ppublish SO - Toxicon. 2003 Sep;42(3):281-8. doi: 10.1016/s0041-0101(03)00143-0.