In Vitro Antioxidant Potential and Effect of a Glutathione‐Enhancer Dietary Supplement on Selected Rat Liver Cytochrome P450 Enzyme Activity

Abstract

Background There is considerable evidence that many people take dietary supplements including those of herbal origin as an alternative therapy to improve their health. One such supplement, with an amalgam of constituents, is CellGevity®. However, the effect of this dietary supplement on drug-metabolizing enzymes is poorly understood, as it has not been studied extensively. Therefore, we investigated the effect of CellGevity dietary supplement on selected rat liver microsomal cytochrome P450 (CYP) enzymes, the most common drug-metabolizing enzymes. We also determined the total antioxidant potential of this dietary supplement in vitro. Methods To determine the antioxidant potential of CellGevity dietary supplement, 2,2-diphenyl-2-picryl-hydrazyl (DPPH), total phenolic, and flavonoid assays were used after initial preparation of a solution form of the supplement (low dose, LD; 4 mg/kg and high dose, HD; 8 mg/kg). Rats received oral administration of these doses of the supplement for 7 days, after which the effect of the supplement on selected liver CYP enzymes was assessed using probe substrates and spectroscopic and high-performance liquid chromatographic methods. Rats which received daily administration of 80 mg/kg of phenobarbitone and distilled water served as positive and negative controls, respectively. Results The IC50 value of the supplement 0.34 ± 0.07 mg/ml compared to 0.076 ± 0.03 mg/ml of the BHT (positive control). The total phenolic content of the supplement at a concentration of 2.5 mg/ml was 34.97 g gallic acid equivalent (GAE)/100 g while its total flavonoid content at a concentration of 2.5 mg/ml was 6 g quercetin equivalent (QE)/100 g. The supplement significantly inhibited rat CYP2B1/2B2 (LDT 92.4%; HDT 100%), CYP3A4 (LDT 81.2%; HDT 71.7%), and CYP2C9 (LDT 21.7%; HDT 28.5%) while it had no significant inhibitory effect on CYPs 1A1/1A2, CYP1A2, and CYP2D6. Conclusion CellGevity dietary supplement possesses moderate antioxidant activity in vitro and has an inhibitory effect on selected rat liver CYP enzymes, suggesting its potential interaction with drugs metabolized by CYP enzymes.

Effect of Cellgevity® Supplement on Selected Rat Liver Cytochrome P450 Enzyme Activity and Pharmacokinetic Parameters of Carbamazepine

“…In the present study (after the 30-day treatment period), Cellgevity® signi cantly increased the activity of rat CYP1A1/2, CYP2C9 and CYP2D6. These results differ from what we earlier reported (11), where Cellgevity® signi cantly inhibited rat CYP3A4, CYP2B1/2B2 and CYP2C9 after a 7-day treatment period.…”

“…The commonest of these interactions appear to occur at the level of drug metabolism; especially with liver microsomal enzymes. We earlier reported that Cellgevity® signi cantly inhibited rat liver CYP3A4, CYP2C9 and CYP2B1/2B2 after a 7-day treatment period (11). On the premise that CYP3A4 was inhibited by Cellgevity® in our earlier research, the current study also sought to determine the effect of Cellgevity® on the pharmacokinetics of carbamazepine (a CYP3A4 substrate) after a 14-day treatment period in SD rats.…”

“…In that study, 4 mg/kg and 8 mg/kg of Cellgevity® were admistered to SD rats over a period of 7 days. Cellgevity® inhibited rat liver CYP3A4, CYP2C9 and CYP1A2, after the 7-day treatment period (11). In the current study, an equivalent dose of Cellgevity® per serving in humans (12.46 mg/kg) was scaled to SD rats (14), and three doses used over a period of 30 days.…”

“…However, there is paucity of scienti c data on the effect of all these constituents (extracts) combined in Cellgevity® on xenobiotic metabolizing enzymes (CYP enzymes). In our earlier study, we reported that Cellgevity® at 4 and 8 mg/kg signi cantly inhibited rat liver CYP2C9, CYP2B1/2B2 and CYP3A4 after a 7-day treatment period (11). In animal models, it is relevant that doses of test agents (drugs/food supplements/herbal products) are at equivalent doses of what pertains in humans.…”

“…We have previously reported that Cellgevity ® inhibited rat liver CYP3A4 after a 7-day treatment period (11). We, therefore, sought to elucidate possible effect of Cellgevity ® on carbamazepine, also known to be extensively metabolized by CYP3A4.…”