TABLE 3

Effect of borneol on in situ formation of oxidative metabolites of valproic acid in sandwich-cultured rat hepatocytes treated with valproic acid

At 120 hours after plating, hepatocytes were pretreated with 1 mM borneol or 0.1% dimethylsulfoxide (DMSO; vehicle) for 0.5 hour. Subsequently, hepatocytes were treated with valproic acid (VPA) (10 or 15 mM) or culture medium (vehicle) in the presence of 1 mM borneol or 0.1% DMSO for 24 hours. Culture supernatants were collected at the end of the 24-hour treatment period and subjected to gas chromatography–mass spectrometry assay for the quantification of the concentrations of oxidative metabolites of VPA. Data are expressed as mean ± S.E.M. for four rats.

Metabolite	In Situ Concentration of VPA Metabolites (µM/0.7 × 10⁶ cells)
	10 mM VPA		15 mM VPA
	0.1% DMSO	1 mM Borneol	0.1% DMSO	1 mM Borneol
4-ene-VPA	0.08 ± 0.01	0.05 ± 0.01^*	0.04 ± 0.01	0.04 ± 0.01
4-keto-VPA	0.09 ± 0.01	0.09 ± 0.02	0.13 ± 0.01	0.16 ± 0.02
4-OH-VPA	3.4 ± 0.56	1.4 ± 0.45^*	2.2 ± 0.22	1.9 ± 0.21
5-OH-VPA	1.6 ± 0.10	0.94 ± 0.05^*	1.7 ± 0.23	1.3 ± 0.19
(E)-2,4-diene-VPA	None detected	None detected	None detected	None detected
(E,Z)-2,3′-diene-VPA	0.19 ± 0.02	0.19 ± 0.02	0.18 ± 0.01	0.20 ± 0.01
(E,E)-2,3′-diene-VPA	1.5 ± 0.09	1.4 ± 0.20	1.6 ± 0.22	1.5 ± 0.14
3-ene-VPA	1.3 ± 0.13	1.2 ± 0.16	1.1 ± 0.13	1.0 ± 0.10
(E)-2-ene-VPA	1.8 ± 0.16	1.9 ± 0.20	2.2 ± 0.29	2.2 ± 0.23
3-OH-VPA	7.1 ± 0.36	6.2 ± 1.5	11 ± 3.1	7.2 ± 1.1
3-keto-VPA	1.4 ± 0.33	1.1 ± 0.35	2.8 ± 0.75	2.1 ± 0.97

↵* Significantly different from the DMSO-cotreated vehicle control group, P < 0.05.