Hepatotoxicity and metabolic effects of cellular extract of cyanobacterium Radiocystis fernandoi containing microcystins RR and YR on neotropical fish (Hoplias malabaricus)

Paulino, Marcelo Gustavo; Rossi, Priscila Adriana; Tavares, Driele; Souza, Naiara Elisabete da Silva de; Sakuragui, Marise Margareth; Moraes, Gilberto; Terezan, Ana Paula; Fernandes, João B.; Giani, Alessandra; Fernandes, Marisa Narciso

doi:10.1016/j.chemosphere.2017.02.089

Cited by 27 publications

(16 citation statements)

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“…The crude extract of R. fernandoi strain 28 containing MC‐YR, MC‐RR, and other oligopeptides is toxic for H. malabaricus . This supports the findings of previous studies (Paulino et al 2017a, 2017b). Acute and subchronic crude extract exposure generates changes in the hepatocytes and whole structural parenchyma of liver.…”

Section: Discussionsupporting

confidence: 93%

“…The characteristic loss of hepatocyte shape from polygonal to rounded shape in H. malabaricus after acute and subchronic exposure to crude extract clearly demonstrated the presence of microcystins in the crude extract. Such a change was already demonstrated in the same species by Paulino et al (2017a, 2017b) and other fish species exposed to purified cyanobacterial toxins or crude extract (Wozny et al 2016; Tavares et al 2018). Hepatocyte hypertrophy and liver hyperemia have also been observed in other fish species (Malbrouck and Kestemont 2006; Wozny et al 2016; Tavares et al 2018), suggesting increased cellular activity and increased energy mobilization to overcome liver dysfunction (Paulino et al 2017a, 2017b).…”

Section: Discussionsupporting

confidence: 52%

“…Effects on energetic metabolism attributable to crude extract have been evaluated by changes of secondary metabolites in the plasma, liver, and white muscles. Incorporation of crude extract also changed the intercellular hepatocyte biliary canaliculi but not the integrity of biliary ducts (Paulino et al 2017a).…”

Section: Introductionmentioning

confidence: 99%

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Biotransformations, Antioxidant System Responses, and Histopathological Indexes in the Liver of Fish Exposed to Cyanobacterial Extract

Paulino

Tavares

Terezan

et al. 2020

Enviro Toxic and Chemistry

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Radiocystis fernandoi, a microcystin (MC) producer, has been common in cyanobacterial blooms in tropical regions. Microcystin is a hepatotoxin that causes tissue damage and even death in animals, including humans; its detoxification process may involve biotransformation and activation of the antioxidant defense system. We evaluated the detoxification pathway, examined the antioxidant defense system responses, and determined the alterations and the organ histopathological indexes in the liver of the tropical fish Hoplias malabaricus after acute and subchronic intraperitoneal exposure to microcystin. The crude microcystin extract of R. fernandoi had predominantly MC‐RR and MC‐YR. The detoxification process was activated by increasing ethoxyresorufin‐O‐deethylase activity, whereas glutathione S‐transferase was inhibited. The activity of the antioxidant defense enzymes superoxide dismutase (SOD) and glutathione peroxidase decreased after acute exposure; the SOD–catalase system and the glutathione level increased after subchronic exposure. The carbonyl protein level, lipid peroxidation (LPO), and DNA damage were unchanged after acute exposure, whereas protein carbonyl was unchanged, LPO decreased, and DNA damage increased after subchronic exposure. Histopathological alteration indexes differed between acute and subchronic exposure, but the histopathological organ indexes indicate liver dysfunction in both exposure periods. We conclude that MC‐RR and MC‐YR induce different liver responses depending on the time of exposure, and the antioxidant defense responses after subchronic exposure may help to partially restore the liver function. Environ Toxicol Chem 2020;39:1041–1051. © 2020 SETAC

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 52%

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Biotransformations, Antioxidant System Responses, and Histopathological Indexes in the Liver of Fish Exposed to Cyanobacterial Extract

Paulino

Tavares

Terezan

et al. 2020

Enviro Toxic and Chemistry

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“…[54] ALT, AST, and LDH enzyme activities serve as sensitive biomarkers in toxicology studies because they provide warning to the aquatic habitats. [25] ALT, AST, and LDH serve as indexes in reflecting pharmacological toxicity. [26,34] Cytolysis of the liver creates changes in the transaminase enzymes.…”

Section: Discussionmentioning

confidence: 99%

“…[19][20][21] Some previous reports proved that adult zebrafish embryos are more suitable to find liver toxicants. [22][23][24] The enzymes responsible for amino acid metabolism in fish are glutamic pyruvic transaminases (ALT) and glutamic oxaloacetic transaminases (AST) enzymes, [25] and their variations in stressed fish can be used as an enzyme indicator to determine cellular dysfunction and cell damage. Similarly, lactic dehydrogenase (LDH) enzyme is also used as a silent indicator of chemical stress and anaerobicity of fish tissue.…”

mentioning

confidence: 99%

Developmental toxicity, antioxidant, and marker enzyme assessment of swertiamarin in zebrafish (Danio rerio)

Sakthivel

Samy

Dharaneedharan

2021

J Biochem & Molecular Tox

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A secoiridoid glycoside called swertiamarin has been widely used as a herbal medicine for many decades. In particular, swertiamarin from the Enicostema axillare herb has been used as a multipurpose drug to treat innumerable health problems. As this medicine is consumed orally, its toxicity level should be determined. To examine the safety of this compound, toxicology work was done in zebrafish, and this is the first report to describe swertiamarin toxicity in zebrafish. Zebrafish embryos were used in this swertiamarin toxicity study, and morphological changes were observed. Further, the compound was also studied in adult zebrafish to determine the impact of the compound on the fish liver.Enzyme profiling with superoxide dismutase, glutathione peroxidase, catalase, reduced glutathione levels, glutathione S-transferase, lactate dehydrogenase, glutamic oxaloacetic transaminases, lipid peroxidation, Na + /K + -ATPase, and glutamic pyruvic transaminases) was evaluated (p ≤ 0.05). Results suggest that swertiamarin is a safe drug only at a low concentration (40 µM). This study also shows that even herbal medicinal compounds may be toxic to humans at higher dosages. Hence, irrespective of whether a drug is synthetic or natural, it needs to be tested for its toxicity before use in humans.

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Role of microRNA‐122 in microcystin‐leucine arginine‐induced dysregulation of hepatic iron homeostasis in mice

Wang

Liu

et al. 2020

Environmental Toxicology

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Microcystin‐leucine arginine (MC‐LR) is a cyclic heptapeptide hepatotoxin produced by cyanobacteria. MicroRNA‐122 (miR‐122) is specifically expressed in the liver. This study focuses on the role of miR‐122 in MC‐LR‐induced dysregulation of hepatic iron homeostasis in C57BL/6 mice. The thirty mice were randomly divided into five groups (Control, 12.5 μg/kg·BW MC‐LR, 25 μg/kg·BW MC‐LR, Negative control agomir and 25 μg/kg·BW MC‐LR + miR‐122 agomir). The results show that MC‐LR decreases the expressions of miR‐122, Hamp, and its related regulators, while increasing the content of hepatic iron and the expressions of FPN1 and Tmprss6. Furthermore, miR‐122 agomir pretreatment improves MC‐LR induced dysregulation of hepatic iron homeostasis by arousing the related regulators and reducing the expression of Tmprss6. These results suggest that miR‐122 agomir can prevent the accumulation of hepatic iron induced by MC‐LR, which may be related to the regulation of hepcidin by BMP/SMAD and IL‐6/STAT signaling pathways.

show abstract

Hepatotoxicity and metabolic effects of cellular extract of cyanobacterium Radiocystis fernandoi containing microcystins RR and YR on neotropical fish (Hoplias malabaricus)

Cited by 27 publications

References 58 publications

Biotransformations, Antioxidant System Responses, and Histopathological Indexes in the Liver of Fish Exposed to Cyanobacterial Extract

Biotransformations, Antioxidant System Responses, and Histopathological Indexes in the Liver of Fish Exposed to Cyanobacterial Extract

Developmental toxicity, antioxidant, and marker enzyme assessment of swertiamarin in zebrafish (Danio rerio)

Role of microRNA‐122 in microcystin‐leucine arginine‐induced dysregulation of hepatic iron homeostasis in mice

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