Safety Evaluation of Green Tea Polyphenols Consumption in Middle‐aged Ovariectomized Rat Model

Abstract

The present work evaluates chronic safety in middle-aged ovariectomized rats supplemented with different dosages of green tea polyphenols (GTP) in drinking water. The experiment used 6-month-old sham (n=39) and ovariectomized (OVX, n=143) female rats. All sham (n=39) and 39 of the OVX animals received no GTP treatment and their samples were collected for outcome measures at baseline, 3 months, and 6 months (n=13 per group for each). The remaining OVX animals were randomized into 4 groups receiving 0.15%, 0.5%, 1%, and 1.5% (n=26 for each) of GTP (wt/vol), respectively, in drinking water for 3 and 6 months. No mortality or abnormal treatment-related findings in clinical observations or ophthalmologic examinations were noted. No treatment-related macroscopic or microscopic findings were noted for animals administered 1.5% GTP supplementation. Throughout the study, there was no difference in the body weight among all OVX groups. In all OVX groups, feed intake and water consumption significantly decreased with GTP dose throughout the study period. At 6 months, GTP intake did not affect hematology, clinical chemistry, and urinalysis, except for phosphorus and blood urea nitrogen (increased), total cholesterol, lactate dehydrogenase, and urine pH (decreased). This study reveals that the no-observed-adverse-effect level (NOAEL) of GTP is 1.5% (wt/vol) in drinking water, the highest dose used in the present study.

Long-term treatment with green tea polyphenols modifies the gut microbiome of female sprague-dawley rats

“…The potential health effects of long-term GTP consumption via drinking water by middle-aged ovariectomized SD rats were evaluated. Results on the chronic safety and clinical observations of the rats supplemented with GTP has been reported recently [30]. This study, focused on the gut microbiota, successfully evaluated both functional genomic and microbial compositional alterations of gut microbiota at two different sampling times, using next-generation sequencing (NGS) technologies.…”

“…This study was conducted concurrently with a recently published study of the chronic toxicity and tolerance of GTP extracts (decaffeinated) among middle-aged ovariectomized rats, in which the experimental design and procedures on chemicals and animal preparations were described [30]. This rat model was developed to evaluate the beneficial effects of long-term GTP supplementation to postmenopausal women.…”

Polyphenols from Food and Natural Products: Neuroprotection and Safety

“…Finally, it is paramount to validate the most promising in vitro data using in vivo models, like toxicologically treated [54,87] or disease-specific [51,56] rodents that could be fed with the original foods, extracts, or isolated bioactive polyphenol molecules. This is also fundamental in assessing the in vivo side effects of polyphenols, particularly in situations mentioned above, and to ascertain the safe usage of any proposed polyphenol [88][89][90][91]. Ultimately, results of in vitro studies, as well as those from animal models, have to be validated by a human pilot study where the beneficial vs. deleterious effects can be monitored, eventually proceeding to clinical trials [92].…”

“…Of these, some studies state that the regular consumption of green tea and green-tea extracts seem to be safe [88], particularly in the form of the traditional infusion [91,103], but the use of concentrated extracts with doses of individual constituents, consumed in solid dosage form, may need additional As stated before, few studies are focused on the toxicity or safety of consuming polyphenols. Of these, some studies state that the regular consumption of green tea and green-tea extracts seem to be safe [88], particularly in the form of the traditional infusion [91,103], but the use of concentrated extracts with doses of individual constituents, consumed in solid dosage form, may need additional study to guarantee their safe use [89]. The direct administration of moderate doses of resveratrol seem to be safe and cardioprotective [104].…”

Tea polyphenols attenuate liver inflammation by modulating obesity-related genes and down-regulating COX-2 and iNOS expression in high fat-fed dogs

“…For example, in a rodent study, Sayama and co-workers [ 38 ] found that green tea lowered triacylglycerol (TAG) levels but did not change TC concentrations. The previous study has shown that the severity of EGCG induced toxicity seems to be a function of dose, administration route and period of treatment [ 39 , 40 ]. Dietary dosages of green tea extract can improve lipid profile and insulin sensitivity and change the genes expression involved in the homeostasis of glucose and lipid [ 41 ].…”