Advances in knowledge of a protein that plays a part in the secretion of drugs residues in milk
Cristina G. Pedraz/DICYT The Biological Application of Drugs Research Group (Biolfar) of the University of León (ULE), led by Julio G. Prieto, is working on the ABCG2/BCRP transport protein, which is expressed in the mammary glands of ruminants and plays a part in the transport of drugs and toxins to milk.
Research on this subject started in 2004 and has continued for the three projects of the National R+D+I Plan. The fourth is currently in progress and is entitled ‘The function and modulation of the ABCG2/BCRP transporter and its polymorphisms in ruminants: the secretion of drugs and nutrients into milk’. Its main researcher is Gracia Merino and it will be completed this year.
One of the researchers of the Group, Ana Isabel Álvarez, explains the interest in working along these lines. “We started this research in response to the economic and sanitary importance of the potential presence of drug residues in milk as this means economic losses for stockbreeders and may generate resistance to antibiotics in consumers. The identification of one of the main factors involved in this process is therefore essential if we are to design strategies to control the presence of drug residues in milk”.
This research over nearly 12 years has allowed the Group to take a closer look at the functioning of the transporter in Holstein cows (a breed of dairy cattle). In some of these animals this ABCG2/BCRP transporter is polymorphic (it exhibits a different form of the same gene), which means that the protein increases its function, i.e. “it is more active in transport to cause the presence of more antibiotic in the milk”. The scientific team from León has also shown how the amount of antibiotic in ovine milk may be reduced by using transport inhibitors in the sheep's diet.
“We know that the passing into milk of a relatively important group of antibiotics used against various infections, including mastitis (an infection of the mammary gland) and which are considered as "residues" in milk, depends on this protein. Moreover, we have also studied the control of its secretion in depth by means of inhibitors. The latter are compounds that may be part of the diet of ruminants and which in addition are considered "bio-healthy" for humans (soya and lignans). For them to act as inhibitors they must be added to the animals' diet for some time, owing to which their level in milk increases as that of the drugs decreases”, the researcher specifies.
The current project, which is now almost complete, has shown that certain compounds, known as endogens to the researchers because they come from the animal itself, appear in large quantities in the milk of polymorphic cows. The objective of the Group is therefore to design a new project in the forthcoming months so as to continue looking into these results and to propose new aims.
Obtaining cell cultures
On the other hand, the development of the various projects of the National R+D+I Plan has allowed the obtaining of cell cultures that present or express the bovine transporter (with its two variants) and the ovine one.
“These cultures have been very useful to us because before going on to experiments with animals we can see whether the transporter can work with the drugs or inhibitors. Standardising this type of procedures saves work in the long run, because it gives you security when carrying out the studies on animals. On the other hand, we have characterised and located polymorphic cows ion farms near León to carry out pharmacokinetic studies and work on secretion into milk”, Álvarez explains.
Public Health implications
The presence of antibiotics in milk is strictly regulated owing to its Public Health implications. It affects not only the quality of the milk; there is also a risk of resistance to medicines being developed in the populations of intestinal bacteria in humans.
The studies carried out by the Biolfar Group therefore have varied implications. Stockbreeders must eliminate milk from an animal treated with any of these antibiotics, and with the advances in knowledge of the ABCG2/BCRP transporter there is a possibility of controlling the presence of pollutants and shortening waiting times.