Influence of kavain on hepatic ultrastructure

Abstract

AIM:To investigate whether the major kavalactone k a v a i n i m p o s e s a d v e r s e e f f e c t s o n t h e l i v e r ultrastructure and function by affecting vascular and microvascular architecture and altering hepatocellular morphology. METHODS:Kavain solution (10 µg/mL or 43.5 µmol/L) was perfused for 2 h in isolated rat livers. After standard fixation and tissue preparation, the samples were examined by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and light microscopy (LM).RESULTS: LM, SEM, and TEM examinations indicated kavain-treated rat livers (n = 4) displayed severe vascular and endothelial damage compared to control livers (n = 4). CONCLUSION:The data so far support the hypothesis that kavain induces adverse effects on liver; additional investigations with other kavalactones and their effects on liver are urgently needed.

Adverse Effects of Drugs and Toxins on the Liver

“…Furthermore, kavalactones inhibit CYP-450 enzymes in vitro (Mathews et al, 2002). Studies in isolated rat livers suggest that kavain (a major kavalactone) is associated with ultrastructural damage (Fu et al, 2008). However, these in vitro and ex vivo data were not supported by the in vivo observation that rats fed with aqueous kava root extracts containing as much as 500 mg kavalactones/kg body weight for 4 wk exhibited no noticeable toxicity (Singh & Devkota, 2003).…”

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

“…The assessment of the efficacy and safety of herbal plants and herbal dietary supplements is important for human health protection (FDA, 2001, 2002; Fong, 2002; Fu et al ., 2008a,b; Parkman, 2002). Although the herbal market has been rapidly growing, data on the identification and toxicological characterization of biologically active constituents in many herbs are lacking.…”

Macrophage depletion ameliorates kavalactone damage in the isolated perfused rat liver

“…The kavalactone concentration selected (43.4 μM) is similar to the EC 50 for cytotoxicity in hepatocytes in vitro (50 μM) (Zou et al, 2004) and was used successfully to induce hepatotoxicity in our previous studies (Fu et al, 2008).…”

“…Our published experiments with kavain-perfused rat livers demostrated swollen macrophages containing large cytoplasmic vacuoles and phagocytosed material, constriction of sinusoidal blood vessels and retraction of the endothelium compared to controls (Fu et al, 2008). The current studies used the same concentration of kavalactones to test the hypothesis that liver macrophages precipitate kavalactone-induced hepatotoxicity.…”

“…At the conclusion of an IPRL experiment, the liver was perfused with 2% glutaraldehyde in 100 mM sodium cacodylate buffer enriched with 100 mM sucrose (Fu et al, 2008;Wisse et al, 2010). Properly fixed tissue (firm and homogeneous brown) was finely sliced with a razor blade into 1 x 1 x 1 mm tissue blocks and stored in cacodylate/sucrose buffer at 4°C for up to one week.…”