Chemotherapy in humans has many neurological side effects, such as depression, anxiety, and short-term memory loss (sometimes called “chemo brain”). It’s believed that inflammation caused by chemo drugs is behind those side effects. But a recent study shows that the time when chemotherapy drugs are given affects the amount of inflammation these drugs cause.
The study, conducted at The Ohio State University’s Wexner Medical Center, showed that timing plays a part in the inflammation. But the results also had one factor that complicates the findings — the inflammatory effects were opposite in the brain versus the spleen depending on the time the drugs were administered.
Timing could be everything
The Ohio State study, published in the journal Scientific Reports, was co-authored by Courtney DeVries, professor of neuroscience at the school. She said, “Timing of drug administration can have a big effect on inflammation, and that may potentially affect a wide variety of harmful human side effects.”
The study used the drugs cyclophosphamide and doxorubicin, both commonly used in breast cancer chemotherapy. Mice were injected with the drugs two hours after daylight (mice are inactive at this time) or two hours after lights were turned off (the mice’s active time).
Researchers then collected tissue and checked for signs of inflammation in the spleen, which is an important immune system organ. They also took tissue from two sites in the brain, the hypothalamus, and the hippocampus.
The researchers found that injecting mice with the chemotherapy drugs in their inactive daylight phase increased the expression of genes that promoted inflammation in the spleen. They found increased production of two toxic drug metabolites. These metabolites are related to inflammation and are products of the chemo drugs.
This kind of inflammation shows itself in side effects such as depression and chemo brain.
The researchers then checked the mice that received the drugs two hours after the lights were turned out. During this period, which is active for mice, inflammation measured in the spleen was much lower than in the mice injected during the day.
This would make you think that timing is critical to avoiding inflammation caused by these drugs. The problem is that the results differed in the brain.
In the brain, the pattern was reversed. Mice injected at night had increases in pro-inflammatory gene expression, but had less inflammation when injected during the day.
The study shows that timing is important with drug delivery. “These findings can’t tell us the best time to administer chemotherapy drugs in humans,” DeVries explained. “But it does demonstrate that time of day is an important factor that needs to be considered in when the drugs are given.”
Despite the divergent results between the spleen and brain with the timing of inflammation, it was noted that the study only used two times. There could be a “sweet spot” somewhere between the times that maximizes the efficacy of the drugs and minimizes the side effects.