Differential Effects of Garlic Oil and Its Three Major Organosulfur Components on the Hepatic Detoxification System in Rats

Abstract

The objective of this study was to compare the modulatory effect of garlic oil and its three organosulfur compounds, diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), on rat hepatic detoxification enzyme activity, and protein and mRNA expression. Rats were orally administered garlic oil (80 or 200 mg/kg bw), DAS (20 or 80 mg/kg bw), DADS (80 mg/kg bw), or DATS (70 mg/kg bw) three times a week for 6 weeks. Control rats received corn oil. According to the results, garlic oil and DAS in dosages of 200 and 80 mg/kg bw, respectively, significantly increased pentoxyresorufin O-dealkylase (PROD) activity as compared with the that of the control rats (P < 0.05). In contrast, N-nitrosodimethylamine demethylase activity in rats that received DADS and DATS was significantly lower than that in the control rats (P < 0.05). Ethoxyresorufin O-deethylase and erythromycin demethylase activities were not influenced by garlic oil, DAS, DADS, or DATS. To the phase II enzyme, garlic oil, DADS, and DATS significantly increased the glutathione S-transferase (GST) activity toward ethacrynic aicd (P < 0.05). Immunoblot assay showed that the protein contents of cytochrome P450 1A1, 2B1, and 3A1 were increased by garlic oil and each of three allyl sulfides, and the change among the allyl sulfides was in the order of DAS > DADS > DATS. The placental form of GST (PGST) level was also increased by garlic oil and the three allyl sulfides, but the increase among the allyl sulfides was DATS congruent with DADS > DAS. P450 2E1, however, was suppressed by each garlic component. Northern blot results indicated that the changes in P450 1A1, 2B1, 3A1, and PGST mRNA levels by garlic components were similar to those noted in the protein levels. These results indicate that the modulatory effect of garlic oil on hepatic drug-metabolizing enzymes can be attributed to its three major allyl sulfide components DAS, DADS, and DATS. These three allyl sulfides vary in modulatory activity, and this variation is related to the number of sulfur atoms in the molecule.

Effects of Garlic Oil on Pancreatic Cancer Cells

“…For the main components of garlic oil, we propose that the active effectors maybe were related to the diallyl sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide (DATS) and others (Wu et al, 2002;Calvo-Gómez et al, 2004;Shin and Cha et al, 2010). Evidence showed that DADS and DATS suppress the growth of multiple cancer types both in vitro and in vivo (Powolny and Singh, 2008;Herman-Antosiewicz et al, 2010;Lee et al, 2011;Altonsy and Andrews, 2011;Altonsy et al, 2012;Wang et al, 2012).…”

Improving the oral bioavailability of beneficial polyphenols through designed synergies

“…Oral administration of a garlic preparation for 3 weeks resulted in a decreased bioavailability of the protease inhibitor saquinavir in healthy subjects [63]. The underlying mechanism was thought to be induction of CYPs, as in vitro studies indicated that the organosulphur compounds from garlic caused induction of CYP1A and 2B, but inhibited CYP2E1 [86] (see [58] for review). Further, tobacco smoke contains polycyclic aromatic hydrocarbons that are known to induce CYP1A2, and the CYP1A2 substrate caffeine is more rapidly cleared in a population of smokers than in nonsmokers [92].…”

Nrf2 Activation, an Innovative Therapeutic Alternative in Cerebral Ischemia

“…(Chen et al, 2004;Fisher et al, 2007;Fukao et al, 2004;Gong et al, 2004;Guyonnet et al, 1999;Kalayarasan et al, 2008;Wu et al, 2002). However, there is no information on Nrf2 induction by these garlic compounds in the brain.…”