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.
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- "The daily application volumes of CP (2 ml/kg body weight) and DADS (5 ml/kg body weight) were calculated in advance based on the most recently recorded body weight of the individual animal. DADS (50 mg/kg/day) was administered daily by gavage to pregnant rats from GD 1–19 (Guyonnet et al., 1999; Wu et al., 2002). CP (7.5 mg/kg) was injected subcutaneously on GD 11 at 1 h after DADS treatment (Gomes-Carneiro et al., 2003). "
ABSTRACT: The protective effects of diallyl disulfide (DADS) on cyclophosphamide (CP)-induced developmental toxicity and the possible mechanisms involved in this protection were investigated in rats. In order to study the mechanisms involved in the protection, we examined the effects of DADS on the expression of cytochrome P450 (CYP) 3A1 in the maternal liver and placenta and oxidative stress in the maternal hepatic tissues caused by CP. CP caused severe embryo-fetal developmental toxicity and hepatic oxidative stress. In contrast, DADS treatment significantly attenuated CP-induced developmental toxicity and oxidative damage in the maternal liver. DADS also significantly increased expression of CYP3A1 in the maternal liver and placenta. These results indicate that the protective effects of DADS against CP-induced developmental toxicity may be due to its ability to promote detoxification of CP, primarily by inducing CYP3A1 expression in the maternal liver and placenta, and its potent antioxidant effects.Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2014; 69. DOI:10.1016/j.fct.2014.04.024 · 2.61 Impact Factor
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- "The CP dose was selected according to previous studies demonstrating significant damage in multi-organ systems of rats [24-26]. The effective DADS dose was based on earlier studies [17,27]. "
ABSTRACT: This study investigated the protective effects of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced testicular toxicity in male rats. DADS was gavaged to rats once daily for 3 days at 100 mg/kg/day. One hour after the final DADS treatment, the rats were given a single intraperitoneal dose of 150 mg/kg CP. All rats were killed and necropsied on day 56 after CP treatment. Parameters of testicular toxicity included reproductive organ weight, testicular sperm head count, epididymal sperm motility and morphology, epididymal index, and histopathologic examinations. The CP treatment caused a decrease in body weight, testicular sperm head count, epididymal sperm motility, and epididymal index. The histopathological examination revealed various morphological alterations, characterized by degeneration of spermatogonia/spermatocytes, vacuolization, and decreased number of spermatids/spermatocytes in the testis, and cell debris and mild oligospermia in the ductus epididymis. In contrast, DADS pretreatment effectively attenuated the testicular toxicity caused by CP, including decreased sperm head count, epididymal sperm motility, and epididymal index and increased histopathological alterations in the testis and epididymis. These results indicate that DADS attenuates testicular toxicity induced by CP in rats.12/2013; 29(4):204-11. DOI:10.5625/lar.2013.29.4.204
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- "The CP dose was selected according to previous studies that demonstrated to induce acute hemorrhagic cystitis in rats (Ozcan et al., 2005). The effective DADS dose was based on earlier studies (Guyonnet et al., 1999; Wu et al., 2002). "
ABSTRACT: This study investigated the protective effects of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced acute urotoxicity in rats. CP caused severe hemorrhagic cystitis as shown by significant increases in bladder weight, edema, and hemorrhage as well as increased urinary bladder epithelial cell apoptosis, protein expression of nuclear factor erythroid 2-related factor-2 (Nrf-2) and phase II enzymes (i.e. quinine oxidoreductase-1 (NQO-1) and heme oxygenase-1 (HO-1)), immunostaining intensity of acrolein-protein adducts, and histopathological changes. The significant decreases in glutathione content and catalase, glutathione-S-transferase, and glutathione reductase activities and a significant increase in malondialdehyde content indicated that CP-induced bladder injury was mediated through oxidative stress. In contrast, pretreatment with DADS significantly attenuated the CP-induced urotoxic effects, including oxidative damage, histopathological lesions, apoptotic changes, and accumulation of acrolein-protein adducts in the bladder. DADS also significantly increased expression of CYP2B1/2, CYP3A1, Nrf-2, NQO-1, and HO-1 and significantly decreased expression of CYP2C11. These results indicate that DADS prevented CP-induced bladder toxicity, in part, by detoxifying acrolein. The protective effects of DADS may be due to its ability to decrease metabolic activation of CP by inhibiting CYP2C11 and inducing CYP3A1, and its potent antioxidant activity and antiapoptotic effects occurred via the Nrf-2-antioxidant response element pathway.Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 11/2013; 64. DOI:10.1016/j.fct.2013.11.023 · 2.61 Impact Factor