The breast cancer resistance protein (BCRP/ABCG2) is an ATP-binding cassette drug efflux transporter that extrudes xenotoxins from cells in intestine, liver, mammary gland, and other organs, affecting the pharmacological and toxicological behavior of many compounds, including their secretion into the milk. The purpose of this study was to determine whether three widely used fluoroquinolone antibiotics (ciprofloxacin, ofloxacin, and norfloxacin) are substrates of Bcrp1/BCRP and to investigate the possible role of this transporter in the in vivo pharmacokinetic profile of these compounds and their secretion into the milk. Using polarized cell lines, we found that ciprofloxacin, ofloxacin, and norfloxacin are transported by mouse Bcrp1 and human BCRP. In vivo pharmacokinetic studies showed that the ciprofloxacin plasma concentration was more than 2-fold increased in Bcrp1^–/– compared with wild-type mice (1.77 ± 0.73 versus 0.85 ± 0.39 μg/ml, p < 0.01) after oral administration of ciprofloxacin (10 mg/kg). The area under the plasma concentration-time curve in Bcrp1^–/– mice was 1.5-fold higher than that in wild-type mice (48.63 ± 5.66 versus 33.10 ± 4.68 min · μg/ml, p < 0.05) after i.v. administration (10 mg/kg). The milk concentration and milk/plasma ratio of ciprofloxacin were 2-fold higher in wild-type than in Bcrp1^–/– lactating mice. We conclude that Bcrp1 is one of the determinants for the bioavailability of fluoroquinolones and their secretion into the milk.

Ingested nitrate leads to the endogenous synthesis of N‐nitroso compounds (NOCs), animal carcinogens with limited human evidence. We aimed to evaluate the risk of colorectal cancer (CRC) associated with nitrate exposure in drinking water and diet. A case‐control study in Spain and Italy during 2008‐2013 was conducted. Hospital‐based incident cases and population‐based (Spain) or hospital‐based (Italy) controls were interviewed on residential history, water consumption since age 18, and dietary information. Long‐term waterborne ingested nitrate was derived from routine monitoring records, linked to subjects’ residential histories and water consumption habits. Dietary nitrate intake was estimated from food frequency questionnaires and published food composition databases. Odd ratios (OR) were calculated using mixed models with area as random effect, adjusted for CRC risk factors and other covariables. Generalized additive models (GAMs) were used to analyze exposure‐response relationships. Interaction with endogenous nitrosation factors and other covariables was also evaluated. In total 1,869 cases and 3,530 controls were analyzed. Average waterborne ingested nitrate ranged from 3.4 to 19.7 mg/day, among areas. OR (95% CIs) of CRC was 1.49 (1.24, 1.78) for >10 versus ≤5 mg/day, overall. Associations were larger among men versus women, and among subjects with high red meat intake. GAMs showed increasing exposure‐response relationship among men. Animal‐derived dietary nitrate was associated with rectal, but not with colon cancer risk. In conclusion, a positive association between CRC risk and waterborne ingested nitrate is suggested, mainly among subgroups with other risk factors. Heterogeneous effects of nitrate from different sources (water, animal and vegetables) warrant further research.

Methylcarbamate benzimidazoles [albendazole (ABZ), fenbendazole (FBZ), and their respective sulfoxide derivatives, albendazole sulfoxide (ABZSO) and oxfendazole (OXF)] are therapeutically important anthelmintic agents with low bioavailability. We studied their in vitro interaction with the apical ATP-binding cassette (ABC) drug efflux transporters, breast cancer resistance protein (BCRP/ABCG2), P-glycoprotein (ABCB1), and MRP2 (ABCC2) using MDCKII cells transduced with human MDR1, MRP2, and BCRP, and murine Bcrp1 cDNAs. These ABC drug efflux transporters extrude a wide range of xenotoxins from cells in intestine, liver, and other organs, thus affecting the bioavailability of many compounds. In transport experiments, ABZSO and OXF were transported efficiently by murine Bcrp1 and moderately by human BCRP, but not by MDR1 or MRP2. ABZ and FBZ were not found to be Bcrp1, MRP2, or P-glycoprotein substrates in vitro. OXF was found to be a good BCRP/Bcrp1 inhibitor, with somewhat higher potency in the MDCKII-BCRP cell line. The latter results were confirmed by flow cytometry experiments demonstrating inhibition by OXF of murine Bcrp1- and human BCRP-mediated mitoxantrone transport. Further studies of interactions between OXF and known BCRP/Bcrp1 substrates will be of interest. The use of efficacious BCRP/Bcrp1 inhibitors might increase the extent and duration of systemic exposure to ABZSO and OXF, with possible therapeutically beneficial effects in extra-intestinal infections.

Today the need to analyze health behaviour from a gender perspective is as imminent as ever, particularly at university, where the number of women who register is on the rise and has exceeded the number of male students worldwide. We carried out a prevalence study aimed at analyzing Spanish university students’ lifestyles and identify differences according to gender and academic discipline. Of 3,646 eligible subjects doing university courses related to health (Group A), education (Group B) and other professions (Group C), 985 (27.0%) participated in the study. Information was elicited about their physical activity level, disturbed eating attitudes, consumption of alcohol, tobacco and illegal substances. Prevalence and Odds Ratios (OR) were calculated according to sex and kind of academic discipline. The obtained data confirmed that only 27.4% of the students were considered as sufficiently active, while 14.9% of them suffered from disturbed eating attitudes (DEA). Women were particularly less active (OR 0.46 (0.32–0.66); p < 0.0001), and more sedentary than men (OR 1.40 (1.00–1.97); p = 0.03). Binge drinking was more frequent in female than in male students (OR 1.79 (1.29–2.47); p = 0.0004). A third of the analyzed sample admitted that they had used illegal substances, while a lower consumption prevalence was found in women (OR 0.53 (0.40–0.71); p < 0.0001). The studied population was not very active (27.4%), especially women (OR = 0.45). Therefore, it seems that Spanish university students lead an unhealthy lifestyle, a situation which seems more conspicuous amongst females.