Adaptive Parotid Gland Hypertrophy Induced by Dietary Treatment of GSE in Rats

Abstract

In a 13-week feeding toxicity study of grape skin extract (GSE) performed previously, 5.0% GSE showed diffuse hypertrophy and basophilia in rat parotid glands. To clarify whether the change in the parotid glands was an adverse effect of GSE, 6-week-old male F344 rats were fed a diet containing 5.0% GSE or were administered a dose corresponding to the dietary concentration via gavage for 4 weeks, and the treatment was stopped for 2 weeks. To ascertain the effect of astringency, other animals were fed a diet containing 5.0% tannic acid (TA) using the same protocol as the GSE feed group. Control groups were fed a basal diet or were administered sterilized distilled water by gavage. In the GSE and TA feed groups, diffuse severe hypertrophy and basophilia in the parotid glandular epithelial cells were observed. Macroscopic, microscopic, and ultrastructural characteristics consistent with cellular hypertrophy was less apparent after the recovery period in both feed groups. In contrast, no changes were observed in the parotid glands of the gavage GSE and control groups at week 4. Based on these findings of parotid hypertrophy without cytotoxicity, the data from this and previous studies suggest that hypertrophy of the parotid glands induced by feeding treatment with GSE is an adaptive non-adverse effect that is reversible upon removal of the sialotrophic agent.

Salivary Gland Adaptation to Dietary Inclusion of Hydrolysable Tannins in Boars

“…Importantly, the morphometric characteristics described above classify the observed parotidomegaly as “hypertrophia” rather than “hyperplasia,” which is defined as an increase in cell number, which was not observed in our study nor previous studies [ 41 ]. A similar reaction within acini was also observed in other studies on pigs [ 42 ] and rats [ 43 ]. Comparable to our results, these studies reported the enlargement of serous acini after feeding tannins to the animals and linked this enlargement to the higher secretory activity of acinar cells and the production of salivary proteins [ 42 , 43 ].…”

“…A similar reaction within acini was also observed in other studies on pigs [ 42 ] and rats [ 43 ]. Comparable to our results, these studies reported the enlargement of serous acini after feeding tannins to the animals and linked this enlargement to the higher secretory activity of acinar cells and the production of salivary proteins [ 42 , 43 ]. Enlargement of salivary gland acini seems to be a common response to external stimuli promoting higher production of saliva or salivary proteins, as shown in the case of Leishmania infantum infection in dogs [ 44 ].…”

Parotid Cells and Infrared Laser. A Morphometric Study

“…It has also been reported that dietary supplementation with grape skin extract in rats (F344/ DuCrj) promotes an increase in the size of the gland and at cellular level the synthesis of larger secretory granules, which is the result of a non-adverse adaptive effect that is reversible once the sialotrophic agent has been eliminated. 23 This evidences a potential promotor effect in the synthesis of the biomolecules contained in these secretory granules. This could be answered under the dose response principle or the Arndt-Schultz principle, which states that low doses of low power infrared laser increase or decrease the physiological functions of a cell, and as the doses or stimuli increase, a plateau is reached where the beneficial physiological effect is suppressed, obtaining an adverse physiological response (Huang, Chen, Carroll, & Hamblin, 2009) (Ispizua, C. G., & Manzanedo, E. S. 2012).…”

Nonclinical safety evaluation of food colorant lac dye via systematic toxicity profiling with assessment of in vivo antigenic potential

“…Unlike our findings, Sakamoto et al reported, without clinical signs for excessive salivation, enlargement and diffuse hypertrophy of acinar cells in the parotid gland accompanying ultrastructural changes in the animals fed with a diet containing 5% lac dye from a 13-week study ( Sakamoto et al, 1998 ; Fukumori et al, 2000 ) with additional involvement of submaxillary gland in the female group in the chronic study ( Sakamoto et al, 2000 ). These changes were considered as an adaptive nonadverse effect caused by unknown stimuli from the diet containing lac dye as also demonstrated in a rodent oral study on a grape skin extract-containing diet based on the reversal of parotid gland hypertrophy after cessation of administration ( Inoue et al, 2013 ; Inoue et al, 2014 ). Acidic solution is known to induce enlargement of salivary glands with salivation ( Cox et al, 1957 ) and the solution containing lac dye had low pH; pH 3.82 for 0.343 mg/ml ( Kongkachuichay et al, 2002 ) and pH 2.56 for 50 mg/ml in this study.…”