Exposure and toxicity of green tea polyphenols in fasted and non-fasted dogs

Abstract

Standardized green tea extract was evaluated for exposure and toxicity in Beagle dogs following oral dosing by capsules. The main component (-)-epigallocatechin gallate (EGCG) accounted for 56-72% of the material. A 9-month chronic study (0, 200, 500, and 1000 mg/kg/day) was done in fasted dogs to take advantage of the reported improved catechin bioavailability with fasting. Extensive morbidity, mortality, and pathology of many major organs led to its early termination at 6.5 months and prevented identification of the toxicity mechanisms. A follow-up 13-week study examined the exposure to and toxicity of the extract. In general, toxicities were less severe than in the chronic study during the same interval. Dosing in a fed state resulted in considerably lower and less variable exposure than found under fasted conditions. Toxicity was less frequent and of lesser severity with lower exposure but limited sample size and large variability prevented reaching that definitive conclusion. Differences in mortality and morbidity between the preliminary terminated chronic and follow-up subchronic studies with the same dose of the same drug lot and similar exposure were not fully resolved as there may be other as yet unclear confounding factors.

Modulators of amyloid protein aggregation and toxicity: EGCG and CLR01

“…Plasma EGCG concentrations in mice tend to be closer to levels reported in human studies compared to levels in rats, in which administration of similar doses results in higher plasma concentrations [188]. Chronic toxicity studies in beagle dogs, showed 67% lethality within 26 weeks of daily doses of 200-800 mg/kg Polyphenon E, a pure and standardized green tea extract, when the dogs fasted for 20 h prior to EGCG administration [193]. However, replication of the 200-mg/kg dose for 13 weeks did not result in any deaths compared to the previous study, in which 3/8 deaths were recorded at that dose [193].…”

“…Chronic toxicity studies in beagle dogs, showed 67% lethality within 26 weeks of daily doses of 200-800 mg/kg Polyphenon E, a pure and standardized green tea extract, when the dogs fasted for 20 h prior to EGCG administration [193]. However, replication of the 200-mg/kg dose for 13 weeks did not result in any deaths compared to the previous study, in which 3/8 deaths were recorded at that dose [193]. Fasting dogs receiving a single dose of 120 mg/kg/day or 400 mg/kg/day died or were sacrificed due to their moribund condition starting at 7 weeks of a 13-week study [190].…”

Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down's syndrome (TESDAD): a double-blind, randomised, placebo-controlled, phase 2 trial

“…In-vitro studies have shown that EGCG is a low-affinity inhibitor of hERG, 26 but in-vivo studies in dogs could not relate these effects to cardiac toxicity. 27 Nevertheless, cardiac toxicity at high doses cannot be excluded and caution should be taken when EGCG is given concurrently with cardiovascular drugs. In our study, we did not see alterations in ECG during EGCG treatment.…”

Aktivitas Polifenol Teh Hijau (Camellia sinensis (L) O. Kuntze) Sebagai Imunomodulator melalui Respons Supresi Imunoglobulin E (IgE) pada Rinitis Alergika

“…EGCG adalah catechins yang paling umum dan paling aktif pada teh hijau dengan konsentrasi fisiologis 0,1-10 mikromolar. 8,[10][11][12] EGCG juga merupakan komponen utama teh hijau yang berperan pula dalam menghambat IL-2 yang bersumber dari sel T. Hambatan ini akan memberi efek pada fungsi IL-2 yang secara normal merespons sel B untuk mengeluarkan antibodi. Salah satu antibodi yang dihambat pengeluarannya adalah IgE sehingga akan mengurangi kadar IgE pada rinitis alergika.…”