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. 2011 Nov;49(11):2820-9.
doi: 10.1016/j.fct.2011.07.067. Epub 2011 Aug 18.

Liver toxicity and carcinogenicity in F344/N rats and B6C3F1 mice exposed to Kava Kava

Mamta Behl  1 , Abraham Nyska, Rajendra S Chhabra, Gregory S Travlos, Laurene M Fomby, Barney R Sparrow, Milton R Hejtmancik, Po C Chan
Affiliations

Liver toxicity and carcinogenicity in F344/N rats and B6C3F1 mice exposed to Kava Kava

Mamta Behl et al. Food Chem Toxicol. 2011 Nov.

Abstract

Kava Kava is an herbal supplement used as an alternative to antianxiety drugs. Although some reports suggest an association of Kava Kava with hepatotoxicity , it continues to be used in the United States due to lack of toxicity characterization. In these studies F344/N rats and B6C3F1 mice were administered Kava Kava extract orally by gavage in corn oil for two weeks, thirteen weeks or two years. Results from prechronic studies administered Kava Kava at 0.125 to 2g/kg body weight revealed dose-related increases in liver weights and incidences of hepatocellular hypertrophy. In the chronic studies, there were dose-related increases in the incidences of hepatocellular hypertrophy in rats and mice administered Kava Kava for up to 1g/kg body weight. This was accompanied by significant increases in incidences of centrilobular fatty change. There was no treatment- related increase in carcinogenic activity in the livers of male or female rats in the chronic studies. Male mice showed a significant dose-related increase in the incidence of hepatoblastomas. In female mice, there was a significant increase in the combined incidence of hepatocellular adenoma and carcinoma in the low and mid dose groups but not in the high dose group. These findings were accompanied by several nonneoplastic hepatic lesions.

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Figures

Figure 1
Figure 1
Photomicrograph of a liver section from a control male rat from the 2 year Kava Kava study. Note (arrows), the normal aspect of the centrilobular hepatocytes. Compare with Figure 1B. X 32. H&E
Figure 2
Figure 2
Photomicrograph of a liver section from a female rat treated with 1 g/kg Kava Kava for 2 years. Note (arrows), mild (grade 2) centrilobular hypertrophy. Compare with Figure 1A. X 32. H&E
Figure 3
Figure 3
Photomicrograph of a liver section from a male rat treated with 1 g/kg Kava Kava for 2 years. Note (arrows), mild (grade 2) cystic degenerationX 16. H&E
Figure 4
Figure 4
Photomicrograph of minimal (grade 1) metaplasia of pancreatic acinar cells to a hepatocytic morphology (arrows) from a female rat treated with 1 g/kg Kava Kava for 2 years. X 16. H&E
Figures 5
Figures 5
Photomicrographs of hepatocellular carcinoma from a male mouse treated with 0.25 mg/kg Kava Kava for 2 years. Figure 5A: Note (arrows), margins of the carcinoma compressing the adjacent normal tissue. X 2. Figure 5B: Higher magnification of Figure 5A. Note (arrows) the trabecular architecture displayed by the neoplastic cells. X 10. H&E
Figures 6
Figures 6
Photomicrograph of hepatoblastoma from a male mouse treated with 1 mg/kg Kava Kava for 2 years (arrows). Note the hyperbasophilic appearance of the mass due to presence of basophilic fusiform cells with a high nucleus to cytoplasmic (N:C) ratio. Fig. 6A: X 2. Figure 6B: x 10. H&E
Figure 7
Figure 7
Photomicrograph of eosinophilic focus (arrows) from a male mouse treated with 0.25 mg/kg Kava Kava for 2 years X 5. H&E
Figure 8
Figure 8
Photomicrograph of angiectasis (arrows) from a male mouse treated with 1 g/kg of Kava Kava for 2 years. X 10. H&E.
See this image and copyright information in PMC

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