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Published on: July 17, 2016
Nephrotoxic effects of chronic administration of microcystins -LR and -YR
Aleksandra Milutinović1, Marko Zivin, Ruda Zorc-Pleskovic
1Institute of Pathophysiology, Medical Faculty of Ljubljana, University of Ljubljana, Zaloska 4, 1000 Ljubljana, Slovenia.
Abstract:
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.
Insights
Chronic exposure to microcystins (MC-LR and MC-YR) causes kidney damage in rats. Cellular changes like cytoskeletal alterations and apoptosis in kidney cells mirror those seen in acute liver injury.
Area of Science:
- Toxicology
- Nephrology
- Cellular Biology
Background:
- Acute microcystin-LR (MC-LR) intoxication damages liver cells via cytoskeletal changes, apoptosis, and necrosis.
- Previous studies suggest chronic exposure to microcystins (MC-LR and MC-YR) can harm both liver and kidneys.
Purpose of the Study:
- To investigate if cytoskeletal alterations, apoptosis, and necrosis are mechanisms behind chronic kidney injury induced by microcystins.
- To compare the nephrotoxic effects of MC-LR and MC-YR in a chronic rat model.
Main Methods:
- Rats received intraperitoneal injections of MC-LR or MC-YR (10 microg/kg) every other day for 8 months.
- Histopathological examination of kidney tissues.
- Rhodamine-phalloidin labeling to assess actin filaments.
- Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) to detect apoptosis.
Main Results:
- Chronic microcystin exposure led to kidney damage, including collapsed glomeruli, thickened basement membranes, and dilated tubules with casts.
- Cytoplasmic aggregation and accumulation of actin filaments were observed in tubular epithelial cells.
- An increased number of TUNEL-positive cells (indicating apoptosis) were found in the kidney cortex and medulla.
- MC-LR induced more severe pathological changes than MC-YR.
Conclusions:
- The cellular mechanisms causing chronic kidney toxicity from microcystins are similar to those causing acute liver toxicity.
- Cytoskeletal disruption and apoptosis are key cellular events in microcystin-induced nephrotoxicity.
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