title: Single sublethal dose of microcystin-LR is responsible for different alterations in biochemical, histological and physiological renal parameters.
abstract: Microcystins (MCYSTs) are very stable cyclic peptidic toxins produced by cyanobacteria. Their effects on hepatic tissue have been studied extensively, and they are considered to be a potent hepatotoxin. However, several effects of MCYST on other organs have also been described, but generally in studies using higher doses of MCYST. In the present work, we investigated the effect of a single sublethal dose of MCYST-LR (55 μg/kg) in Wistar rats and analyzed different aspects that influenced renal physiology, including toxin accumulation, excretion, histological morphology, biochemical responses and oxidative damage in the kidney. After 24 h of exposure to MCYST-LR, it was possible to observe an increased glomerular filtration rate (6.28 ± 1.56 vs 2.16 ± 0.48 μl/min per cm(2)) compared with the control group. Increase of interstitial space and collagen deposition corresponded to a fibrotic response to the increased production of reactive oxygen species. The observed decrease of Na(+) reabsorption was due to inhibition of the activity of both Na(+) pumps in proximal tubules cells. We suggested that this modulation is mediated by the effect of MCYST as a phosphatase protein inhibitor that maintains the sustained kinase-mediated regulatory phosphorylation of the ATPases. The observed alteration of Na(+) active transporters lead to damage of renal function, since are involved in regulation of water and solute reabsorption in proximal tubules. The results of this report reinforce the importance of understanding the molecular effects of a single sublethal dose of MCYST-LR, which, in this study, was responsible for macro-alterations found in the renal parenchyma and renal physiology in rats.
authors.affiliation: Laboratory of Biological Physical Chemistry, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: J
authors.initials: J
authors.lastname: Lowe
authors.forename: J
authors.initials: J
authors.lastname: Souza-Menezes
authors.forename: D S
authors.initials: DS
authors.lastname: Freire
authors.forename: L J
authors.initials: LJ
authors.lastname: Mattos
authors.forename: R C
authors.initials: RC
authors.lastname: Castiglione
authors.forename: C M L
authors.initials: CM
authors.lastname: Barbosa
authors.forename: L
authors.initials: L
authors.lastname: Santiago
authors.forename: F M
authors.initials: FM
authors.lastname: Ferrão
authors.forename: L H D
authors.initials: LH
authors.lastname: Cardoso
authors.forename: R T
authors.initials: RT
authors.lastname: da Silva
authors.forename: H J
authors.initials: HJ
authors.lastname: Vieira-Beiral
authors.forename: A
authors.initials: A
authors.lastname: Vieyra
authors.forename: M M
authors.initials: MM
authors.lastname: Morales
authors.forename: S M F O
authors.initials: SM
authors.lastname: Azevedo
authors.forename: R M
authors.initials: RM
authors.lastname: Soares
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D000458:Cyanobacteria / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008387:Marine Toxins; D052998:Microcystins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D008387:Marine Toxins; D052998:Microcystins; D017382:Reactive Oxygen Species; D000254:Sodium-Potassium-Exchanging ATPase; C057862:cyanoginosin LR; D005978:Glutathione