Hepato-renal toxicity of Myristica fragrans Houtt. (Myristicaceae) seed extracts in rats

Objectives: Myristica fragrans is used in many parts of the world as a common spice and herbal medicine for managing a wide variety of ailments. The rich nutritional factors in M. fragrans seeds show potential application in food biofortification; however, the long-term safety of using a high dose of the seeds needs to be validated. This study seeks to investigate how oral administration of high doses of methanol (ME) and n-hexane (NHE) extracts of M. fragrans seed for one or two weeks affects the histology and serum markers of kidney and liver of rats. Methods: Adult male Swiss mice (6-7 weeks, 20-30 g) were used for acute toxicity study by standard methods, while male Wistar rats (6-8 weeks, 100-120 g) were used for sub-acute toxicity test. The sixty rats were distributed into five groups of 12 rats each: Group 1 received normal saline, groups 2 and 3 were orally treated with 500 and 1000 mg/kg b.w/day ME while groups 4 and 5 were fed 500 and 1000 mg/kg b.w/day NHE, respectively for 14 days. Six rats from each group were sacrificed on days 8 and 15 after 24 h of fasting. Markers of kidney and liver status of test and control animals were compared using one-way analysis of variance. Results: The presence of terpenoids, flavonoids, alkaloids, phenols, steroids, and tannins were detected in both extracts, although at varying levels. There was no obvious sign of toxicity nor mortality in acute toxicity test after 24 h of administration of extracts up to 5000 mg/kg b.w. However, there were significant (p < 0.5) elevations in urea, total bilirubin and creatinine concentrations, alkaline phosphatase, aspartate and alanine aminotransferases, and lactate dehydrogenase activities in rats fed extracts for seven or fourteen days relative to control. Furthermore, the n-hexane extract at 1000 mg/kg elicited some histological changes consistent with hepatotoxicity. Conclusions: Although the extracts were rich in some essential phytochemicals, this study demonstrated that long-term administration of high doses of the extracts elicits hepato-renal toxicities. Hence, consuming a large amount of the seed over a long duration is discouraged. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).