A poison that heals
Discovering the therapeutic potential of hydrogen sulfide
Most of us think of hydrogen sulfide, known for its rotten egg smell, as a poisonous gas harmful to human health. While it can be lethal in large quantities, it is also part of a family of small molecules called gasotransmitters that are produced in our own bodies.
Dr. Alp Sener, transplant surgeon in the Multi-Organ Transplant Program at LHSC and scientist at Lawson Health Research Institute, is using controlled doses of these molecules to pioneer new solutions to health-care challenges.
The inspiration for Dr. Sener’s research on hydrogen sulfide and kidney transplantation came in part from a paper in the academic journal Science that his father showed him while he was still an undergraduate student.
The paper focused on the protective effects of hydrogen sulfide in hibernating animals. Hydrogen sulfide levels increase in animals when they hibernate and hibernation-like states can be induced in these animals by administering hydrogen sulfide.
Years later, during his postdoctoral training, Dr. Sener made a connection between the findings in the paper and the hibernation-like state that kidneys and other organs go into when they are being preserved in cold temperatures before transplant. He wondered what role hydrogen sulfide could play in improving this process.
Now Dr. Sener has investigated this question to address a major issue in kidney transplantation.
“Everywhere in the world there is a large discrepancy between the number of patients on the kidney transplant waiting list and the number of available organs,” says Dr. Sener. “Due to the lack of donor supply we often have to use ‘marginal’ deceased donor kidneys, which can be kidneys from older donors, donors with existing medical issues, and donors after circulatory death (loss of function of the heart and lungs). These kidneys often don’t work as long and are slower to recover after transplantation.”
After a kidney is taken from a donor, the typical process to prepare the organ for transplant can cause further injury to the cells and tissues. This process involves flushing the kidney with cold preservation solution and then putting it in cold storage for an average of 18-24 hours while it is being transported to the recipient.
Dr. Sener and his research team found that if hydrogen sulfide molecules are added to the preservation solution, organ storage can be prolonged without risk of tissue injury. Dangerous inflammatory cells decrease, kidney function is recovered quicker after transplant, the kidneys have greater urine output, and the rate of survival is improved.
This method would be easy to implement. The hydrogen sulfide molecule, which is already approved for use in renal failure patients, is simply added to existing organ preservation solutions. The drug is given directly to the organ while it is in storage.
“Our goal is to make these donor kidneys work better, quicker and longer. Instead of a kidney lasting 10 years, what if our treatment could make it last 11? One year doesn’t seem like a lot but that means a patient doesn’t need to go on dialysis for another year, they can travel or continue to work. It means a lot for a patient’s quality of life, not to mention the significant economic impact that dialysis has on our health-care system.”
While he is now a leader in this growing field, Dr. Sener says it was hard convincing people at first that hydrogen sulfide, a smelly toxic molecule, could be used to improve kidney transplantation.
“When we started this research a lot of people said it was a crazy idea. We spent many years determining the correct dosage for therapeutic benefit to ensure there were no toxic effects. As this research becomes more mainstream, we hope it will eventually help improve outcomes of organ transplantation all over the world.”
This article is adapted from Lawson Link magazine. To learn more about the use of gasotransmitters in health research, visit www.lawsonresearch.ca/lawsonlink.