Subchronic toxicity of lyophilized apoaequorin protein powder in Sprague-Dawley rats

Abstract

Apoaequorin is a bioluminescent calcium-binding apoprotein endogenous to the Aequorea species of jellyfish and is commercially available in a dietary supplement in support of brain and cognitive health. Results from a previous 90-day subchronic oral gavage study established the no-observed-adverse-effect-level (NOAEL) of lyophilized apoaequorin protein powder (LAPP) at 666.7 mg/kg/day. The current 90-day oral gavage study in Sprague-Dawley rats administered dose levels of 1000, 2000, and 4000 mg/kg/day of test substance as received. These doses are expressed as milligram of supplement with the amounts of apoaequorin based on the analysis of the percentage of active ingredient. The corresponding amounts of apoaequorin protein are 603, 1206, and 2412 mg/kg/day. These dose levels target approximately 4221, 8442, and 16,844 times more than the expected human oral intake. There were no mortalities, clinical observations, ophthalmological, clinical pathology, or histopathological changes attributable to LAPP administration. Changes in mean body weight and feed efficiency, without other correlating clinical or pathological or other toxicologically relevant findings, were considered to be of little toxicological significance. Therefore, the NOAEL for LAPP administered orally up to 90 days was 4000 mg/kg/day (2412 mg/kg/day based on 603 mg/g or 60.3% active ingredient, apoaequorin protein), the highest dose tested in male and female rats.

Polymerized Whey Protein Concentrate-Based Glutathione Delivery System: Physicochemical Characterization, Bioavailability and Sub-Chronic Toxicity Evaluation

“…However, this phenomenon was only observed in one time point and later returned to normal. Similar phenomenon was also observed in the experiment of Bauter et al [ 49 ], and it was interpreted as having no toxicological relevance and no side effects. In contrast, no change in the food consumption was observed in the male groups.…”

“…In blood biochemical tests, although there were significant differences in some data compared with the control group, there was no correlation between these changes in the organism and the dose of chemical exposure, so the effect was considered to be independent of the exposure [ 49 ].…”

“…As shown in Figure 5 , histopathological findings observed consisted of degeneration of some pyramidal cells in the brain and the c; local slight dilatation of myocardial fiber tract space; focal inflammatory cell infiltration in the liver; renal tubular epithelial cell edema; slight degeneration of the testicular tubules. These lesions are very mild and mostly spontaneous in animals used in the experiment [ 43 , 49 ]. Therefore, these results were independent of the use of PWPC-GSH which could be observed in the age and strain of the rats used in this study.…”