Sex differences in the effects of microsomal enzyme inducers on hepatic phase I drug metabolism in the rat

Skett, Paul; Paterson, Pauline

doi:10.1016/0006-2952(85)90729-4

Cited by 15 publications

(2 citation statements)

References 23 publications

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“…The change (improvement) in GSRH on Q100 was not significant in the total sample (see Table 3). However, sex differences in drug effects are common (Golomb, 2013;Golomb & Evans, 2008;Golomb, Evans, Dimsdale, & White, 2012;Golomb & Koperski, 2013a, 2013bGolomb, Koperski, & White, 2012), including in drug classes relevant to GWV (Menich, Costello, Hoffman, Hershey, & Engler, 2001;Pittman, 2002;Schieszer, 2003) and extending to drug transporters and metabolizing enzymes (Classen & Netter, 1985;Finnen & Hassall, 1984;Ofotokun, 2005;Skett & Paterson, 1985;Xiang et al, 2011). The study sample was predominantly male (85%, comparable to the 83% overall GWV with fatiguing illness who were male (Kang, Natelson, Mahan, Lee, & Murphy, 2003)), and male sex significantly predicted GSRH change in the total sample (p = 0.031).…”

Section: Resultsmentioning

confidence: 97%

Coenzyme Q10 Benefits Symptoms in Gulf War Veterans: Results of a Randomized Double-Blind Study

et al. 2014

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We sought to assess whether coenzyme Q10 (CoQ10) benefits the chronic multisymptom problems that affect one-quarter to one-third of 1990-1 Gulf War veterans, using a randomized, double-blind, placebo-controlled study. Participants were 46 veterans meeting Kansas and Centers for Disease Control criteria for Gulf War illness. Intervention was PharmaNord (Denmark) CoQ10 100 mg per day (Q100), 300 mg per day (Q300), or an identical-appearing placebo for 3.5 ± 0.5 months. General self-rated health (GSRH), the primary outcome, differed across randomization arms at baseline, and sex significantly predicted GSRH change, compelling adjustment for baseline GSRH and prompting sex-stratified analysis. GSRH showed no significant benefit in the combined-sex sample. Among males (85% of participants), Q100 significantly benefited GSRH versus placebo and versus Q300, providing emphasis on Q100. Physical function (summary performance score, SPS) improved on Q100 versus placebo. A rise in CoQ10 approached significance as a predictor of improvement in GSRH and significantly predicted SPS improvement. Among 20 symptoms each present in half or more of the enrolled veterans, direction-of-difference on Q100 versus placebo was favorable for all except sleep problems; sign test 19:1, p=0.00004) with several symptoms individually significant. Significance for these symptoms despite the small sample underscores large effect sizes, and an apparent relation of key outcomes to CoQ10 change increases prospects for causality. In conclusion, Q100 conferred benefit to physical function and symptoms in veterans with Gulf War illness. Examination in a larger sample is warranted, and findings from this study can inform the conduct of a larger trial.

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Section: Resultsmentioning

confidence: 97%

Coenzyme Q10 Benefits Symptoms in Gulf War Veterans: Results of a Randomized Double-Blind Study

et al. 2014

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“…Neither testosterone nor 5 -DHT had a significant effect on either total GST or isoenzyme M1-1/M1-2 activity. As ethanol, used as a vehicle for all the hormones tested except GH, is known to induce the activities of certain enzymes involved in the metabolism of xenobiotics (Skett & Paterson 1985, Okey 1990), its effect on GST activities in co-cultured hepatocytes was investigated. Ethanol at a final concentration of 0·1% (equivalent to that present in the medium during treatment of cells with testosterone, 5 -DHT, OE 2 or T 3 ) had no significant effects on either total or Mu-class M1-1/M1-2 GST activities.…”

Section: Effect Of Hormones On Gst Activitiesmentioning

confidence: 99%

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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Prepubertal Regulation of the Rat Dioxin-Inducible Aldehyde Dehydrogenase (ALDH3)

Stephanou

Pappas

Vasiliou

et al. 1999

Advances in Experimental Medicine and Biology

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Sex differences in the effects of microsomal enzyme inducers on hepatic phase I drug metabolism in the rat

Cited by 15 publications

References 23 publications

Coenzyme Q10 Benefits Symptoms in Gulf War Veterans: Results of a Randomized Double-Blind Study

Coenzyme Q10 Benefits Symptoms in Gulf War Veterans: Results of a Randomized Double-Blind Study

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

Prepubertal Regulation of the Rat Dioxin-Inducible Aldehyde Dehydrogenase (ALDH3)

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