Comparison of in vivo and in vitro toxic effects of microcystin-LR in fasted rats

Miura, George A.; Robinson, Nancy; Geisbert, Thomas W.; Bostian, Karen A.; White, James R.; Pace, J.

doi:10.1016/0041-0101(89)90031-7

Cited by 85 publications

(52 citation statements)

References 26 publications

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“…Moreover, the specific activities of acid phosphatase and succinate dehydrogenase, respective markers for lysosomal and mitochondrial membranes, were significantly increased after the treatment with MCLR. These results are in agreement with previous studies reporting functional changes in lysosomal and mitochondrial hepatic membranes from rodents treated with microcystins (11,18).…”

Section: Discussionsupporting

confidence: 94%

“…Therefore, the observed increase in the production of oxygen free radicals in the intestine of MCLR-treated rats could contribute to intestinal damage (14), with alteration in cellular membrane organization, membrane fluidity and modification in the activity of intestinal membrane enzymes. In this sense, the fluidity of hepatic microsomal membranes from mice (11) and hepatic mitochondrial membrane from rats (18), has been reported to be affected by the exposure to MCLR.…”

Section: Discussionmentioning

confidence: 99%

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Influence of Microcystin-LR on the activity of membrane enzymes in rat intestinal mucosa

Moreno

Mate

Repetto

et al. 2003

J. Physiol. Biochem.

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I. M. MORENO, A. MATE, G. REPETTO, C. M. VÁZQUEZ and A. M. CAMEÁN. Influence of Microcystin-LR on the activity of membrane enzymes in ratintestinal mucosa. J. Physiol. Biochem., 59 (4), [293][294][295][296][297][298][299][300] 2003.The objective of the present study was to evaluate the effects of microcystin-LR (MCLR) on the activity of membrane enzymes from intestinal mucosa. In addition, serum chemistry and peroxidative status of both serum and intestinal homogenate were evaluated after treatment with MCLR. Wistar rats were treated with intraperitoneal injection of either 100 µg pure MCLR/Kg body weight or saline solution. A significant increase in liver weight and altered serum enzyme activities were found in MCLR-treated rats, indicating damage to the liver in these rats, as previously suggested. A higher specific activity of sucrase (1.5-fold) was observed after the administration of MCLR, whereas other intestinal apical membrane enzymes, such as lactase, maltase and alkaline phosphatase were not modified by the treatment. The specific activities of acid phosphatase and succinate dehydrogenase, markers for lysosomal and mitochondrial membranes, respectively, were also increased (32% and 60%, respectively) in treated rats. The analysis of lipid peroxidation showed that the peroxidative status was increased in both serum and intestinal mucosa from MCLRtreated rats, reflecting an excess production of oxygen free radicals induced by this cyanobacterial toxin. In conclusion, this study shows that acute exposure to MCLR affects the intestinal physiology by modifying the intestinal peroxidation status as well as the activity of membrane enzymes.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Influence of Microcystin-LR on the activity of membrane enzymes in rat intestinal mucosa

Moreno

Mate

Repetto

et al. 2003

J. Physiol. Biochem.

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“…Contrary to the in vitro results obtained in rat liver mitochondria by Miura et al (1989), where no effects were observed for the tested concentrations, the present study showed significant effects on the in vitro studies with rat kidney isolated mitochondria treated with MC-LR.…”

Section: Discussioncontrasting

confidence: 99%

“…Furthermore, this MPT can be inhibited by cyclosporin A and DTT, which unequivocally proves that the observed swelling induced by MC-LR was due to MPT pore. Miura et al (1989) have previously demonstrated that liver mitochondria isolated from fasted rats treated with MC-LR showed alterations in appearance which was correlated with a loss of coupled electron transport. Liver mitochondria from toxin treated, fasted rats exhibited complete inhibition of state 3 respiration, while those from toxin-treated, fed rats had ADP/O ratios and respiratory control indices comparable to the control values (Miura et al, 1991).…”

Section: Discussionmentioning

confidence: 96%

Mitochondria a key role in microcystin‐LR kidney intoxication

La-Salete

Oliveira

Palmeira

et al. 2007

J of Applied Toxicology

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Microcystins (MCs) are a group of closely related cyclic heptapeptides produced by a variety of common cyanobacteria. These toxins have been implicated in both human and livestock mortality. Microcystin-LR could affect renal physiology by altering vascular, glomerular and urinary parameters, indicating that MC-LR could act directly on the kidney. The aim of the current work was to examine the effect of MC-LR on mitochondrial oxidative phosphorylation of rat kidney isolated mitochondria.Furthermore, microcystin-LR decreased both state 3 and carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP)-uncoupled respiration. The transmembrane potential was strongly depressed by MC-LR in a concentration dependent manner, pointing to an uncoupling effect; however, microcystin-LR did not increase the permeability of the inner mitochondria membrane to protons. Therefore, the transmembrane decrease was a consequence of a strong inhibitory effect on redox complexes. The addition of uncoupling concentrations of MC-LR to Ca 2+ + + + + -loaded mitochondria treated with ruthenium red resulted in mitochondrial permeability transition pore (MPTP) opening, as evidenced by mitochondrial swelling in isosmotic sucrose medium. Mitochondrial swelling in the presence of Ca 2+ + + + + was prevented by cyclosporin A and was drastically inhibited by catalase and dithiothreitol, indicating the participation of mitochondrial generated reactive oxygen species in this process. From this study it can be concluded that the bioenergetic lesion promoted by microcystin-LR seems to be sufficient to explain renal injury.

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“…In a variety of animals, exposure to a lethal dose of toxin produces blood-engorged livers, which exhibit diffuse centrilobular necrosis (Konst et al, 1965;Jackson et al, 1984;Adams et al, 1988). The hepatotoxic effects of Microcystis toxins have been described in both rats and mice (Dabholkar and Carmicnael, 1987;Miura et al, 1989). Fasted rats injected ip with 100 Ag/kg of MCYST-LR exhibit bloodengorged livers after 60 min and die within 2 hr .…”

Section: Introductionmentioning

confidence: 99%