Identification of human liver mitochondrial aldehyde dehydrogenase as a potential target for microcystin-LR

Chen, Ting; Cui, Jun; Liang, Yan; Xin, X.B.; Young, D. Owen; Chen, Chun; Shen, Pingping

doi:10.1016/j.tox.2005.12.001

Cited by 60 publications

(31 citation statements)

References 45 publications

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“…Patients were exposed intravenously to water containing MC, causing the death of a large number of patients (Fischer et al, 2005;Chen et al, 2006). By being able to promote a range of adverse effects and, in some cases, cause death of individuals, the World Health Organization (WHO) established a maximum acceptable limit of MC-LR in drinking water as 1 μg L -1 and for foods from 0.04 μg Kg -1 day -1 as Tolerance Daily Intake (TDI) of MC (WHO, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…Once inside the organism, the target organ of the MC is the liver and it may enter hepatocytes by two different routes: the bile acid receptor (Chen et al, 2006) or by Organic Anion Transporting Polypeptide (OATPs) (Fischer et al, 2005). However, other organs such as the gastrointestinal tract, kidney and brain also exhibit these transporters (Pasková et al, 2008), thus increasing the number of targets for this toxin.…”

Section: Introductionmentioning

confidence: 99%

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Biochemical and genetic alterations in the freshwater neotropical fish Prochilodus lineatus after acute exposure to Microcystis aeruginosa

Garcia

Martinez

2012

Neotrop. ichthyol.

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Microcystins are secondary metabolites produced by different species of cyanobacteria, such as Microcystis aeruginosa (MA). In this study, the biochemical and genetic effects of lyophilized MA were evaluated in the neotropical fish Prochilodus lineatus exposed to 1 or 2 mg L -1 lyophilized MA (treated group) or only water (control group) in static toxicity tests for 24 and 96 h. The gills and liver were used in the analysis of biotransformation enzymes and antioxidant defenses, blood and gill cells in genetic analysis and in brain and muscle it was determined the activity of acetylcholinesterase (AChE). The results showed the biotransformation pathway activation due to the increase in hepatic CYP1A and in branchial and hepatic glutathione Stransferase (GST). The antioxidant defense proved to be greatly affected by MA exposure leading to changes, both in gills and liver, in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and in the content of tripeptide glutathione (GSH). Lipid peroxidation was not detected, but damage to DNA molecule was observed in blood cells. In conclusion, it can be state the lyophilized MA is able to promote changes in the biochemical and genetic parameters of P. lineatus.As microcistinas são metabólitos secundários produzidos por diferentes espécies de cianobactérias, como a Microcystis aeruginosa (MA). Neste estudo, os efeitos bioquímicos e genéticos de liofilizado de MA foram avaliados para juvenis da espécie de peixe Neotropical Prochilodus lineatus expostos a 1 ou 2 mg L -1 de liofilizado de MA (grupo tratado) ou apenas à água (grupo controle), em testes de toxicidade estáticos, durante 24 e 96 h. As brânquias e o fígado foram usados para as análises das enzimas de biotransformação e defesas antioxidantes, células do sangue e das brânquias para análises genéticas e no cérebro e músculo foi determinada a atividade da acetilcolinesterase (AChE). Os resultados mostraram ativação da via de biotransformação devido ao aumento da atividade da CYP1A hepática e da atividade da glutationa S-transferase (GST) hepática e branquial. As defesas antioxidantes foram muito afetadas pela exposição a MA levando a alterações, tanto no fígado como nas brânquias, na atividade da superóxido dismutase (SOD), da catalase (CAT), da glutationa peroxidase (GPx), glutationa redutase (GR) e no conteúdo do tripeptídeo glutationa (GSH). Apesar dessas alterações a peroxidação lipídica não foi detectada em nenhum dos tecidos, mas danos na molécula de DNA foram observados nas células do sangue. Em conclusão, pode-se afirmar que o liofilizado de MA é capaz de promover alterações em parâmetros bioquímicos e genéticos de P. lineatus.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biochemical and genetic alterations in the freshwater neotropical fish Prochilodus lineatus after acute exposure to Microcystis aeruginosa

Garcia

Martinez

2012

Neotrop. ichthyol.

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“…It was also demonstrated that microcystin could bind to ATP synthase, an important component in the mitochondria (Mikhailov et al, 2003). Human liver mitochondrial aldehyde dehydrogenase is also a potential target for microcystin-LR (Chen et al, 2006), pointing to the relevance of mitochondria in microcystin toxicity.…”

Section: Discussionmentioning

confidence: 99%

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 this study, the solvent used in extraction of MC-LR was water:methanol:butanol (75:20:5) because of efficiencies of extraction of different structure variant of MC were increased with their hydrophobicity , [21,22] shown that the polar extracts (water: methanol:butanol) have higher contents of MC because of MC polarity, therefore, MCs are soluble in water:methanol:butanol.…”

Section: Discussionmentioning

confidence: 99%

The Biochemical Alteration and Dna Damage in Rats (Rattus Rattus) After Chronic Intraperitoneally Injection to Purified Microcystin-Lr From Anabaena Circinalis

Khadairi

Al-amari

Almamoori

2017

Asian J Pharm Clin Res

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Objective: This study determined the effect of purified microcystin-leucine arginine (MC-LR) on biochemical and DNA damage parameters in rats.Methods: Utilization of preparative high-performance liquid chromatography in analysis, purification and collection of MC-LR, then intraperitoneally injection of purified MC-LR to rats. At the end of exposure, animals were sacrificed, and liver cell was isolated to measure the biochemical markers such as superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) as well as measured malondialdehyde (MDA), reactive oxygen species (ROS) and cytochrome P450 (Cyt P450), and DNA damage markers such as comet length, tail length, and tail moment were measured with the single cell gel electrophoresis also called comet assay. Results:The present results showed significantly increased activities of SOD as well as concentration of MDA, ROS with increasing concentration of MC-LR but the activities of CAT and GSH, as well as Cyt P450, were significantly decreased with increasing MC-LR dose while makers of DNA damage such as comet length, tail length, and tail moment also significantly increased with increasing MC-LR dose. Conclusion:This study demonstrated that chronic exposure to MC-LR toxin can induce alteration of biochemical and DNA damage markers.

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Identification of human liver mitochondrial aldehyde dehydrogenase as a potential target for microcystin-LR

Cited by 60 publications

References 45 publications

Biochemical and genetic alterations in the freshwater neotropical fish Prochilodus lineatus after acute exposure to Microcystis aeruginosa

Biochemical and genetic alterations in the freshwater neotropical fish Prochilodus lineatus after acute exposure to Microcystis aeruginosa

Mitochondria a key role in microcystin‐LR kidney intoxication

The Biochemical Alteration and Dna Damage in Rats (Rattus Rattus) After Chronic Intraperitoneally Injection to Purified Microcystin-Lr From Anabaena Circinalis

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