Hepatic cytosolic glutathione S-transferase activities in ageing Brown Norway rats — Importance of sex differences and phenobarbital treatment for studies of ageing

Coecke, Sandra; Vandenberghe, Yves; Callaerts, A.; Sonck, Walter; Verleye, Gino; Bezooijen, C.F.A. van; Vercruysse, Antoine; Rogiers, Vera

doi:10.1016/0047-6374(90)90026-c

Cited by 14 publications

(6 citation statements)

References 18 publications

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“…In rat, total and Mu-class GST activities (Hales & Neims 1976, Hatayama et al 1986, Coecke et al 1990, and the amounts of GST proteins, in particular M1 and M2 , Igarashi et al 1987, and of the corresponding mRNAs (Igarashi et al 1987, Pickett et al 1987 are higher in male than in female liver. However, here we found no effect of the male sex hormones testosterone and 5 -DHT on the activities or amounts of GST proteins in co-cultured male rat hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Such hormone-related differences in GST expression may provide a molecular basis for tissue, gender, age and interindividual differences in the toxicity of certain xenobiotics (Lock et al 1984, Coecke et al 1990, Singhal et al 1992. The effects of the different hormones under investigation are most pronounced for the Mu-class GSTs.…”

Section: Discussionmentioning

confidence: 99%

“…The separation and quantification of GST subunits was carried out according to Vandenberghe et al (1990), using an LC10 system (Shimadzu, Berelux, 's-Hertogen-bosch, Netherlands) with a Prolinea 4/33 HPLC-dedicated integrator (Compaq, Houston, TX, USA). The GST subunits were identified by comparison of the retention time obtained for the individual peaks with those of purified GST subunits and by comparison of the patterns generated with characteristic extrahepatic GST profiles and previously published GST HPLC profiles (Hiratsuka et al 1990, Vandenberghe et al 1990, Meyer et al 1991, Johnson et al 1990, 1993, Kispert et al 1989, Meyer et al 1989. GST subunits were quantified using peak areas of the respective subunits from HPLC, together with molecular masses (Mannervik & Danielson 1988) and molar extinction coefficients at 214 nm, as given by Johnson et al (1992).…”

Section: Isolation and Separation Of Gst Subunitsmentioning

confidence: 99%

“…At present, no ideal hepatocyte culture system exists. However, previous work by our group has shown that hepatocytes co-cultured with rat-liver epithelial cells of primitive biliary origin maintain the expression of many differentiated liver functions and may provide a useful model for studying enzyme regulation (Vandenberghe et al 1988a, Rogiers et al 1990, Akrawi et al 1993, Coecke et al 1993, Rogiers 1993, Rogiers & Vercruysse 1993. In this paper, we report the use of adult rat hepatocytes co-cultured with rat-liver epithelial cells of biliary origin, to distinguish between direct and indirect effects of various hormones on GSTs, to identify the GST subunits affected by individual hormones, and to investigate the level at which each hormone acts.…”

Section: Introductionmentioning

confidence: 99%

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Hormonal regulation of glutathione S-transferase expression in co-cultured adult rat hepatocytes

Coecke¹,

Vanhaecke²,

Foriers³

et al. 2000

Journal of Endocrinology

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Glutathione S-transferases (GSTs) are subject to regulation by thyroid and sex hormones and by GH. We have used an in vitro experimental system comprising adult rat hepatocytes co-cultured with rat liver epithelial cells of primitive biliary origin, to distinguish between direct and indirect effects of various hormones on GSTs; to identify the GST subunits affected by individual hormones; and to investigate the level at which the hormones act. Triiodothyronine (T 3 ), thyroxine (T 4 ) and 17 -oestradiol (OE 2 ) reduced GST activities, whereas testosterone, dihydrotestosterone, and human growth hormone (hGH) had little effect on total GST activity. HPLC separation of the various GST subunits revealed that T 3 and T 4 reduced total GST content, in particular the abundance of subunits M1 and M2. The amount of the Pi-class subunit P1 was reduced by OE 2 . Treatment of the co-cultured cells with this hormone altered the GST subunit profile to one that is more similar to that observed in freshly isolated hepatocytes. Analysis of mRNAs demonstrated that some of the hormones act at a pre-translational level, whereas others act at a translational or post-translational level to regulate the expression of various GST subunits.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Isolation and Separation Of Gst Subunitsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hormonal regulation of glutathione S-transferase expression in co-cultured adult rat hepatocytes

Coecke¹,

Vanhaecke²,

Foriers³

et al. 2000

Journal of Endocrinology

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“…Rat studies have found decreased CYP2E1 activity in old age , which could result in reduced formation of the unidentified toxic intermediates and oxidative free radicals. The detoxification of these toxic intermediates may also be altered as GST activity has been seen to be either decreased or unchanged with old age in rodents .…”

Section: Introductionmentioning

confidence: 99%

The effect of ageing on isoniazid pharmacokinetics and hepatotoxicity in Fischer 344 rats

Mach

Pajkos

Mitchell

et al. 2015

Fundamemntal Clinical Pharma

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Isoniazid is the first-line treatment for tuberculosis; however, its use is limited by hepatotoxicity. Age-related differences in isoniazid pharmacokinetics and hepatotoxicity are uncertain. We aimed to investigate these in young (3 ± 0 months, n = 26) and old (23.0 ± 0.2 months, n = 27) male Fischer 344 rats following a low- or high-dose toxic regimen of isoniazid or vehicle (4 doses/day over 2 days; low: 100, 75, 75, 75 mg/kg; high: 150, 105, 105, 105 mg/kg i.p. every 3 h). Fifteen hours after the last dose, animals were euthanized and sera and livers were prepared for analysis. Isoniazid treatment increased serum hepatotoxicity markers (alanine and aspartate transaminase) in young animals but not in old animals, and only reached significance with the high dose in young animals. Isoniazid treatment caused a trend towards an increase in necrosis in young animals with both doses. In contrast, microvesicular steatosis was increased in old isoniazid-treated animals, reaching significance only with the low dose (steatosis prevalence in old: vehicle 1/9, isoniazid 4/5; P < 0.05). Among isoniazid-treated animals, concentrations of toxic intermediates acetylhydrazine and hydrazine were higher in old than young animals (P < 0.05). With both doses, hepatic cytochrome P450 2E1 activity was higher in young animals compared with old (P < 0.05). There were no other age effects seen on any of the other measured enzymes involved in isoniazid metabolism (N-acetyl transferase, amidase, glutathione-S-transferase). These results show age-related changes in isoniazid pharmacokinetics may contribute towards differential patterns of toxicity and confirm that standard hepatotoxicity markers do not detect isoniazid-induced microvesicular steatosis.

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Drug Hepatotoxicity in the Elderly

Kitani¹

1996

Handbook of Experimental Pharmacology

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Hepatic cytosolic glutathione S-transferase activities in ageing Brown Norway rats — Importance of sex differences and phenobarbital treatment for studies of ageing

Cited by 14 publications

References 18 publications

Hormonal regulation of glutathione S-transferase expression in co-cultured adult rat hepatocytes

Hormonal regulation of glutathione S-transferase expression in co-cultured adult rat hepatocytes

The effect of ageing on isoniazid pharmacokinetics and hepatotoxicity in Fischer 344 rats

Drug Hepatotoxicity in the Elderly

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