Evaluation of triclosan exposures on secretion of pro-inflammatory cytokines from human immune cells

Wilburn, Wendy; Jamal, Sara; Ismail, Farah; Brooks, Dylan; Whalen, Margaret M.

doi:10.1016/j.etap.2021.103599

Cited by 17 publications

(19 citation statements)

References 57 publications

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“…CIA mice were treated with SS (40 mg/kg) at ZT6 (corresponding to low drug efficacy) or ZT18 (corresponding to high drug efficacy), and with TGT (30 mg/kg) at ZT2 (corresponding to high drug efficacy) or ZT14 (corresponding to low drug efficacy) (Figures 5, 6). Pharmacokinetic analysis of SS focused on four constituents (i.e., brucine, strychnine, pseudostrychnine, and pseudobrucine) and one metabolite (dihydroxystrychnine from strychnine) that can be quantified as noted previously (Zhao et al, 2020a;Gao et al, 2021). Plasma levels of brucine and strychnine after SS dosing at ZT18 were significantly higher than those after drug dosing at ZT6, particularly in the first 30 min (Figures 5A,B).…”

Section: Dosing Time-dependent Pharmacokinetics Of Ss and Tgtmentioning

confidence: 87%

“…Supporting this, the levels of inflammatory factors such as IL-6 (the marker of rheumatoid arthritis) display diurnal oscillations with a peak level in the morning (Ingpen, 1968). Notably, circadian variation in the severity of disease is a potential factor contributing to time-varying drug effects (Zhao et al, 2020a). It was thus necessary to minimize this confounding effect on the chronoefficacy of SS and TGT as the efficacy against arthritis was mainly measured by changes in the levels of inflammatory factors.…”

Section: Discussionmentioning

confidence: 99%

“…Although SS and TGT are therapeutically beneficial in the treatment of rheumatoid arthritis, their toxicities to certain organs have been noted (Zhao et al, 2020a;Gao et al, 2021). SS mainly causes injuries in the kidney and brain, thereby generating nephrotoxicity and neurotoxicity (Gao et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…Plasma samples were collected through retro-orbital bleeding at predetermined time points (i.e., 5, 15, 30, 60, 120, 360, and 720 min). All plasma samples were processed for UPLC-QTOF/MS analysis as previously described (Zhao et al, 2020a;Gao et al, 2021). AUC (area under the curve) and other pharmacokinetic parameters were obtained by using WinNonlin software (Pharsight, Cary, NC, United States) with the non-compartmental method.…”

Section: Pharmacokinetic Studiesmentioning

confidence: 99%

“…Intriguingly, circadian clock has been shown to regulate drug pharmacokinetics, resulting in time-varying drug efficacy and/or toxicity (Ohdo, 2003;Lin et al, 2019a;Yang et al, 2020). Circadian pharmacokinetics is often times associated with diurnal expression of drugmetabolizing enzymes (Gachon and Firsou, 2011;Zhao et al, 2020a). For example, diurnal CYP3A11 regulated by BMAL1 accounts for circadian metabolism and chronotoxicity of many drug substrates such as aconitine, triptolide, and brucine (Lin et al, 2019a;Yang et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics-Based Chronoefficacy of Semen Strychni and Tripterygium Glycoside Tablet Against Rheumatoid Arthritis

et al. 2021

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Rheumatoid arthritis is a systemic autoimmune disease characterized by synovial inflammation and bone destruction. Identifying drugs with time-varying efficacy and toxicity, and elucidating the mechanisms would help to improve treatment efficacy and reduce adverse effects. Here, we aimed to determine the chronoefficacy of semen strychni (SS) and tripterygium glycoside tablet (TGT) against rheumatoid arthritis in mice, and to investigate a potential role of circadian pharmacokinetics in generating chronoefficacy. SS extract and TGT suspension were prepared with ultrasonication. Effects of SS and TGT on collagen-induced arthritis (CIA) were evaluated by measuring TNF-α and IL-6 levels. SS dosed at ZT18 was more effective in protecting against CIA than drug dosed at ZT6 (i.e., lower levels of key inflammatory factors at ZT18 than at ZT6). This was accompanied by higher systemic exposure levels of strychnine and brucine (two main putative active ingredients of SS) in ZT18-treated than in ZT6-treated CIA mice. TGT dosing at ZT2 showed a better efficacy against CIA as compared to herb doing at ZT14. Consistently, ZT2 dosing generated a higher exposure of triptolide (a main putative active ingredient of TGT) as compared to ZT14 dosing in CIA mice. Moreover, strychnine, brucine, and triptolide significantly inhibited the proliferation of fibroblast-like synoviocytes, and reduced the production of TNF-α and IL-6 and the mRNAs of TNF-α, IL-6, COX-2, and iNOS, suggesting that they possessed an anti-arthritis activity. In conclusion, SS and TGT display chronoefficacy against rheumatoid arthritis in mice, that is attributed to circadian pharmacokinetics of main active ingredients. Our findings have implications for improving treatment outcomes of SS and TGT via timed delivery.

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Section: Dosing Time-dependent Pharmacokinetics Of Ss and Tgtmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%