Effect of recombinant human thymosin-alpha1, an immuno-modulating peptide with 28 amino acids, on the activity of cytochrome P450s.
Wang. Bing B; He. Fan F; Lin. Yu Y; Huang. Min M; Zhou. Shu-Feng SF
Key Findings
- In vitro, thymosin‑alpha‑1 (20‑50 µM) significantly inhibited rat CYP2E1 activity.
- In vivo, two weeks of sub‑cutaneous thymosin‑alpha‑1 increased CYP2E1 activity and, at the highest dose, also raised CYP1A2, CYP2D2, and CYP3A1/2 activities.
- No change in liver weight was observed, indicating the effects are enzymatic rather than toxic.
Practical Outcomes
- If you’re using thymosin‑alpha‑1, be aware it could alter the metabolism of drugs processed by CYP2E1, CYP1A2, CYP2D6, or CYP3A4, potentially changing their effectiveness or side‑effects. Consider timing or monitoring other medications and supplements, especially those cleared by these pathways, until human data become available.
Summary
Researchers tested thymosin‑alpha‑1 in rats and found it can change the activity of several liver enzymes that break down drugs. In test‑tube experiments it blocked one enzyme (CYP2E1), while in live rats it actually boosted that enzyme and a few others after two weeks of daily injections. This suggests the peptide might affect how other medicines are processed, but we don’t yet know if the same happens in people.
Abstract
There is an increasing application of protein/peptide drugs in the treatment of various diseases such as cancer and autoimmune diseases in clinical settings. However, data is scant on the potential for modulation of cytochrome P450s (CYPs) by these protein/peptide drugs. In this study, we examined the effects of recombinant human thymosin-alpha1 (rh-T alpha 1) on hepatic cytochrome P450 (CYP) enzyme activity in rats in vitro and in vivo. For the in vitro experiments, rh-T alpha 1 was incubated with the probe drugs and the liver microsomes from rats, while rh-T alpha 1 was administered to rats subcutaneously at 150, 300, or 600 microg/kg daily for two weeks in in vivo studies. The activities of six rat hepatic CYP enzymes, namely CYP1A2, CYP2C6, CYP2C11, CYP2D2, CYP2E1, and CYP3A1/2, were determined by a cocktail of probe drugs including phenacetin (O-deethylation), tolbutamide (4-hydrolylation), omeprazole (5-hydroxylation), dextromethorphan (O-demethylation), chlorzoxazone (6-hydroxylation), and nifedipine (N-dehydrogenation), respectively. Co-incubation of rh-T alpha(1) at the concentration of 20 and 50 micromol/l with the liver microsomes significantly inhibited CYP2E1 activity, whereas there was no significant effect on the activities of CYP1A2, CYP2C6, CYP2C11, CYP2D2, and CYP3A1/2. As to in vivo studies, treatment of rh-T alpha 1 at either dosage did not significantly alter the liver weight. However, an ex vivo study demonstrated that the activity of rat hepatic CYP2E1 was significantly increased by pretreatment of rh-T alpha 1 at the three doses for two weeks, and the activities of CYP1A2, CYP2D2, and CYP3A1/2 were also significantly increased in rats pretreated with rh-T alpha 1 at 600 microg/kg. These data indicate that rh-T alpha 1 can modulate the activities of major rat CYP isoforms, and further studies are needed to investigate its effect on human CYP activities and the potential for causing drug interactions.
Study Information
pubmed
2007
2007-07-31T00:00:00.000Z
10.2174/187231207781369825
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