Gastrointestinal and Systemic Uptake of Bismuth in Mice after Oral Exposure

Abstract

The aim of this study was to screen the inhibitory potential of different clinically used oestrogen and progestin hormones on CYP2C9, 2C19 and 3A4 activities in human liver microsomes. The degree of inhibition by desogestrel, 3-ketodesogestrel, 17-beta-oestradiol, gestodene, aethinyloestradiol, medroxyprogesterone acetate, norethisterone or L-norgestrel were studied at 100 microM on losartan oxidation (CYP2C9), R-omeprazole 5'-hydroxylation (CYP2C19) and R-omeprazole sulphoxidation (CYP3A4) with a 10-min preincubation with NADPH in human liver microsomes prepared from 6 individual genotyped donor livers. Aethinyloestradiol was found to be a potent inhibitor (55% mean inhibition; 95% CI 32% to 79%) of losartan oxidation (CYP2C9) and R-omeprazole 5-hydroxylation (70%; 63% to 77%) (CYP2C19), while it had little effect on R-omeprazole sulphoxidation (CYP3A4) activity. 17-beta-Oestradiol did not produce significant inhibition on any of the studied enzyme activities. Of the progestin hormones studied, gestodene and 3-ketodesogestrel were potent inhibitors of CYP2C19 (57%; 47% to 67% and 51%; 29% to 45%) and CYP3A4 (45%; 30% to 59% and 40%; 19% to 62%), but had little effect on the CYP2C9 activity. In addition, medroxyprogesterone acetate was found to inhibit CYP2C9 (55%; 45% to 65%), while not having significant effect on 2C19 or 3A4. In conclusion, the liability of clinically used female sex steroids to inhibit CYP2C9, 2C19 and 3A4 activities in human liver microsomes is very distinctive and these differences among both the oestrogen and progestin hormones may, at least in part, explain the variable results from clinical trials examining inhibitory effects of hormone replacement therapy and oral contraceptives on drug metabolism.

Radiobismuth for Therapy

“…All radionuclides have specific in vivo sites of deposition which when free pose as a source of toxicity concerns. Bismuth is very well established to have high affinity for localization in the kidney [34].…”

Radiation Dose Enhancement Using Bi2S3 Nanoparticles in Cultured Mouse PC3 Prostate and B16 Melanoma Cells

“…Bi is one of the least expensive heavy metal-based NPs and is significantly cheaper than Au. It has a low level of toxicity and has been used in biological applications, [20] and pharmaceuticals formulations for the treatment of gastrointestinal disorders, [21] eradication of Helicobacter pylori in peptic ulcers, [22][23][24] syphilis, tumours, [25] and the reduction of cisplatin-induced renal toxicity [26]. Even when exposed to the highest dose of bismuth subsalicylate used to treat stomach disorders (~4.2 g BSS/kg) the plasma concentrations of salicylate were found to be well below toxic levels [27].…”