Treatment of acute pancreatitis is one of the pressing issues in modern medicine. Patients feel immense amounts of pain, which only addictive drug substances can help relieve. Sometimes the load on body is so high that it cannot cope with it and multiple organ failure occurs, followed by intensive care or fatal outcome. In some cases surgery is required, and this is also a difficult decision to be made since pancreas surgery has high mortality risks.
A group of medical professionals and biologists from Chelyabinsk and Ekaterinburg have performed a systematic analysis of experimental works on the new approaches to acute pancreatitis treatment using rodents models, published over three decades. The team included: Director of the SUSU China-Russia Research Centre for System Pathology Aleksei Sarapultsev, academician of the Russian Academy of Sciences Valerii Chereshnev, and expert surgeon Maksim Rantsev. After careful selection, nine controlled experimental research studies out of 541 obtained publication records were used for the qualitative analysis.
“For the joint first author of the article, Maksim Rantsev, this topic is not only of experimental, but also of clinical importance: he is an operating surgeon with many years of experience in the surgical pathology of the abdominal cavity organs. This research has become part of his thesis. That is why it was not an abstract question, whether one could influence the early mechanisms of inflammation in case of acute pancreatitis before the disease takes on a severe form featuring necrosis, systemic complications, or a need for surgery,” shares Aleksei Sarapultsev.
As a result, the researchers have published a paper on neuromodulatory expert influencing at the early stages of acute pancreatitis.
Neuromodulatory expert influencing means influencing the nervous system for pancreas treatment.
According to the scientists, the blockade of serotonin receptors looks most promising. It might seem that the body is already in a poor condition, whereas serotonin is often called a “feel-good” hormone. Unfortunately, it is not the case for pancreas: in the context of inflammation, serotonin may increase tissue damage and boost the inflammatory reaction.
The first test that such patients undergo at an admission ward in order to diagnose pancreatitis is the blood test for amylase and lipase. Namely these enzymes reveal the “disaster scale” with regards to the pancreas condition.
The lab rats and mice were administered medications that blocked the serotonin receptors, and the levels of blood amylase and lipase decreased by 37–65%, while the edema and death of the pancreas cells reduced.
The scientists also anchor hopes in such medication as L-17 thiadiazine. This is directly related to surgery: using this substance, the 7-day death rate of rodents after pancreas surgery dropped from 50–70% to 30%. This new medication not just inhibited inflammation, it switched the composition of the immune cells in the lesion from destructive granulocytes to reparative monocytes and lymphocytes.
The third option is ferroptosis, a certain type of cells death when the damage increases due to aberration of iron metabolism and oxidative stress. In one of the experimental works, olanzapine demonstrated the protective effects. This medication is primarily known of as an antipsychotic agent. However, in this case it is not stated that this medication should be administered to pancreatitis patients: in the model, the effect is considered as an example of influencing the cell mechanisms of damage and not as a ready-for-use clinical treatment regimen.
The medications were administered to rodents either in the beginning of the experiment (before they got pancreatitis), or at the very early stage of the disease – and then those proved to be effective. But in real life it almost never happens this way. Till a person realizes the seriousness of the situation and that the pain will not disappear on its own, till they call an ambulance, till the patient is taken to gastroenterology department and examined by a surgeon…Usually, 24 hours pass between the first symptoms are detected and the treatment is started. And no such therapeutic window was added in the experiments with rodents considered by the scientists.
There are also great many other factors causing things to “go sideways” in case of human beings, unlike in rodents. So, we still have a long way to go from experimental hypotheses to implementation in the clinical practice.
“It’s still early to talk about a ready-for-use treatment. But our work shows which mechanisms are worth testing further: serotonin regulation of inflammation, the stress axis, and the ferroptosis. For clinical surgery, this is important namely as a search for early intervention strategies, which in the future could help decrease the severity of acute pancreatitis before irreversible complications develop,” believes Aleksei Sarapultsev.
This research study has been published in the Diseases international medical journal, included in Q1 of the world’s scientific periodical publications according to Scopus.