Effects of three fungicides alone and in combination on glutathione S-transferase activity (GST) and cytochrome P-450 (CYP 1A1) in the liver and gill of brown trout (Salmo trutta)

Almli, B.; Egaas, Eliann; Christiansen, Anne; Eklo, O.M; Lode, O; Källqvist, Torsten

doi:10.1016/s0141-1136(02)00157-5

Cited by 19 publications

(7 citation statements)

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“…Thus, it may be argued that the slightly different toxicokinetic properties between the two might be responsible for small differences in enzymatic changes and differences in hepatotoxic potential, especially if we are aware that both imazalil and cypermethrin were administered under the same conditions (time ⁄ doses ⁄ animals). Similar findings with approximately the same doses and time of exposure were found in other vertebrates [28][29][30][31][32]. Consequently, from these results, we established a graded array of toxic potential characteristic for each individual pesticide (cyp > im > car).…”

Section: Discussionsupporting

confidence: 77%

“…This is a very feasible explanation of differences in (decreased) enzyme activities between the combination groups, as it is known that imazalil induces CYP 1A1 and inhibits CYP 3A4 and generally acts as an inhibitor of biotransformational enzymes. Carbendazim inhibits CYP 2D6, and for cypermethrin, it is known that it has little effect on at least eight different cypenzimes in the living organism [31–39]. In fact, the histological finding proves that the combinations of pesticides until the 28th day probably killed cells that contribute to the total serum activity sooner than individual pesticides evoked necrotic changes.…”

Section: Discussionmentioning

confidence: 99%

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Carbendazim Impends Hepatic Necrosis when Combined with Imazalil or Cypermethrin

Đikić

Landeka

Knežević³

et al. 2011

Basic Clin Pharma Tox

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Imazalil, cypermethrin and carbendazim are detected in plants for human nutrition. To explore whether their combinations, applied orally in low doses, would induce changes in metabolic patterns and hepatotoxicity, a subchronic in vivo experiment was conducted. Doses of 10 mg ⁄ kg of imazalil (im) and cypermethrin (cy) and 20 mg ⁄ kg of carbendazim (car) and their combinations (im, 10 mg ⁄ kg + cy, 10 mg ⁄ kg; im, 10 mg ⁄ kg + car, 20 mg ⁄ kg; car, 20 mg ⁄ kg + im, 10 mg ⁄ kg) were given to Swiss mice daily over 28 days. After 24 hr from the last dose, the relationships of cytotoxicity biomarkers were analysed: serum lactate dehydrogenase, aspartate transaminase, alanine transferase, amylase, alkaline phosphatase, creatine kinase, creatinine and total proteins. Individual pesticides showed different toxic potential (cy > im > car) generally characterized by increase in enzyme activities. Histological analysis showed that cypermethrin, but not imazalil or carbendazim, alone can cause mild necrosis. Combinations generally caused decrease in the activity of enzymes, indicating liver damage. Low doses of carbendazim in combination with low doses of imazalil or cypermethrin caused very pronounced hepatic necrosis, more than any of the three individually applied pesticides or combination of imazalil and cypermethrin. In fruits and vegetables for human consumption, residues of these three pesticides and prolonged combined intake of low doses, which by themselves acutely would not cause any effect, may have similar hepatotoxic effects.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Carbendazim Impends Hepatic Necrosis when Combined with Imazalil or Cypermethrin

Đikić

Landeka

Knežević³

et al. 2011

Basic Clin Pharma Tox

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“…More than 14 types of fresh water fish are present in the lower part of the river Nile. Depending on the in vitro substrate selected, GST activity may be registered in fish tissues such as liver (Dominey et al 1991;Gallagher and Di-Giuilio 1992;Hamed et al 1999;Angelucci et al 2000;Melgar Riol et al 2001;Novoa-Valinas et al 2002), gills (Nimmo 1985;Al-Ghais and Ali 1995;Almli et al 2002) and kidney (Nimmo and Spalding 1985;Novoa-Valinas et al 2002). Several studies have been undertaken in the recent past to investigate the nature and function of hepatic GST in rainbow trout, Oncarhynchus mykiss, Atlantic salmon, Salmo salar and brown trout, Salmo trutta (Ramage and Nimmo 1984;Lauren et al 1989;Novoa-Valinas et al 2002), Sturgeon, Acipenser baeri (PerduDurand and Cravedi 1989), rainbow trout hepatocytes (Melgar Riol et al 2001), channel catfish, Ictalurus punctatus (Gallagher and Di-Giuilio 1992) and other fish found in mostly temperate waters.…”

Section: Introductionmentioning

confidence: 99%

Glutathione and its Related Enzymes in the Nile Fish

Hamed

Maharem

Guinidi

2004

Fish Physiol Biochem

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Glutathione (GSH) and related enzymes, glutathione transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GR) form an important phase 2 biotransformation enzymes system. The objective of this study was to compare this enzymes system in three fish species from the river Nile, Oreochromis niloticus, Claris lazera and Cyprinus carpio in order to establish the main differences and to purify and characterize GST from the liver of O. niloticus.The level of GSH and the activity of GST, GPx and GR in the liver, kidney and gills of the three fish species were examined. A simple reproducible procedure for the purification of GST from the liver of O. niloticus to homogeneity, which includes chromatography on DEAE-cellulose followed by affinity chromatography on GSH-sepharose was established. The molecular mass was found to be 25,460 Da by SDS-PAGE. The MichaelisMeneten constants (K m ) of the enzyme for GSH and CDNB were 0.35 mM and 0.42 mM, respectively. The affinity purified enzyme exhibited maximum pH at pH 8.0 and increasing pH above 8.0 did not affect the observed maximum. The purified enzyme acts readily on CDNB, less readily on some standard transferase substrates (1,2-dichloro-4-nitrobenzene and p-nitrophenethyl bromide) and not at all on others (bromosulphophthalein and p-nitrobenzyl chloride). Bromosulfophthalein, cibacron blue and hematin inhibited CDNB-conjugating activity of the purified enzyme with IC 50 0.079, 3.98 and 0.126 lM, respectively.

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“…Carbendazim inhibits CYP 2D6, and for cypermethrin it is known that it has little effect on at least eight different CYP enzymes in the living organism. [52][53][54][55][56][57][58][59][60] Whether these inhibitions or activations of biotransformation enzymes create more metabolites and whether some of these metabolites can cause DNA damage is unknown but substantially assumed. Besides, changes in liver cytotoxicity markers were different and specific in all treated groups and indicate that there is a toxic disturbance in hepatocyte homeostasis (Table 1).…”

mentioning

confidence: 99%

Carbendazim combined with imazalil or cypermethrin potentiate DNA damage in hepatocytes of mice

et al. 2011

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Traces of pesticides imazalil, cypermethrin and carbendazim are detected in plants used for human consumption. To explore whether their application in oral combinations will induce DNA breaks in hepatocytes, a subchronic in vivo experiment was performed in Swiss mice. Doses of 10 mg kg(-1) of imazalil (im) and cypermethrin (cy), and 20 mg kg(-1) of carbendazim (car) and their combinations (im, 10 mg kg(-1) + cy, 10 mg kg(-1); im, 10 mg kg(-1) + car, 20 mg kg(-1); car, 20 mg kg(-1) + cy, 10 mg kg(-1)) were applied daily for 28 days. Afterward, DNA damage in hepatocytes was evaluated by comet assay. Individually, imazalil and cypermethrin damaged DNA at alkali-labile sites, while the tail moment (TM) of carbendazim alone was similar to control but with higher tail length. In combination with carbendazim clastogen, properties of imazalils and cypermethrins were potentiated compared to all other treatments and control. There were pronounced sex differences in pattern of fragmentation between treated groups. Higher long tail nuclei (LTN) in females indicate that certain cells in females were especially prone to total nucleus disintegration. Due to synergistic effects, low environmentally present concentrations of imazalil and cypermethrin in food, and especially their mixtures with carbendazim have genotoxic potential that could be particularly dangerous over prolonged exposure in mammalian organism.

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Effects of three fungicides alone and in combination on glutathione S-transferase activity (GST) and cytochrome P-450 (CYP 1A1) in the liver and gill of brown trout (Salmo trutta)

Cited by 19 publications

References 1 publication

Carbendazim Impends Hepatic Necrosis when Combined with Imazalil or Cypermethrin

Carbendazim Impends Hepatic Necrosis when Combined with Imazalil or Cypermethrin

Glutathione and its Related Enzymes in the Nile Fish

Carbendazim combined with imazalil or cypermethrin potentiate DNA damage in hepatocytes of mice

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