Substances that protect cultured hepatocytes from the toxic effects of microcystin-LR

Thompson, WL; Pace, JG

HERO ID

1190257

Reference Type

Journal Article

Year

1992

Language

English

PMID

20732161

HERO ID 1190257
In Press No
Year 1992
Title Substances that protect cultured hepatocytes from the toxic effects of microcystin-LR
Authors Thompson, WL; Pace, JG
Journal Toxicology In Vitro
Volume 6
Issue 6
Page Numbers 579-587
Abstract Primary cultures of rat hepatocytes were used in a screen in vitro for agents which protect against the toxic effects of the hepatoxin microcystin-LR. Exposure of cells to microcystin-LR, a cyclic heptapeptide produced by blue-green algae, resulted in clustering of hepatocytes within 15 min of addition. This initial response was followed by disruption of cellular function (measured by a protein synthesis assay) and eventual loss of membrane integrity, resulting in leakage of cytosolic enzymes (measured by LDH release). The antibiotic rifampicin was effective in reducing LDH release and preventing cell clustering at concentrations as low as 2.0 mum. Cytochalasins provided some protection at 10 mum. However, microscopy revealed disruption of hepatocytes in the presence of cytochalasins alone, at or above this concentration. Bile acids, cholic acid and deoxycholate were protective at higher concentrations (0.1 mm), but when given alone caused some leakage of cytosolic enzymes. Di-naphthalene dyes, trypan blue and trypan red, had no detrimental effects on hepatocytes and showed some protection at 20 mum. Hepatic uptake of tritium-labelled microcystin-LR was suppressed by bile acids and rifampicin, providing further evidence that blocking or competing with bile acid uptake also prevents microcystin-LR association with, and toxicity in, isolated hepatocytes. Although all drugs tested worked to varying degrees, rifampicin was most effective in providing protection of hepatocytes from toxin at lower concentrations while having no detrimental effects on the cells when added alone.
Doi 10.1016/0887-2333(92)90071-X
Pmid 20732161
Wosid WOS:A1992KE96700014
Url <Go to ISI>://WOS:A1992KE96700014
Is Certified Translation No
Dupe Override No
Comments Source: Web of Science WOS:A1992KE96700014Scopus URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-0027062881&doi=10.1016%2f0887-2333%2892%2990071-X&partnerID=40&md5=9d2fdc6ea0d2c8baaefffef5d11ec8c0
Is Public Yes
Language Text English
Keyword bile acid; cholic acid; cyanoginosin lr; cytochalasin; deoxycholic acid; rifampicin; animal cell; article; cell culture; liver cell; nonhuman; priority journal
Is Qa No