Olaparib Reduces Organ Damage in Sepsis

A recently published article in Experimental Biology and Medicine (Volume 246, Issue 17, September, 2021) examines the role of olaparib in sepsis. The study, led by Dr. Quan Li, in the Department of Anesthesiology at the National Clinical Research Center for Cancer and Shenzhen Hospital in Shenzhen (China), reports that olaparib, a poly (ADP-ribose) polymerase inhibitor, improves survival and reduces organ damage in an animal model of sepsis.
Sepsis is a complex disease involving the host immune response to infectious agents. Sepsis results in life-threatening organ dysfunction and has a high fatality rate in intensive care units. Studies have shown that early organ injury in sepsis results from excessive inflammatory reactions, and uncontrolled inflammation is a key step in disease progression. Recent studies have shown that olaparib, which is FDA-approved for the treatment of some cancers, has beneficial effects on organ injury following inflammation. Nonetheless, its mechanism of action in sepsis has not been delineated.
In this study, Dr. Li and colleagues examined the effects of olaparib in an animal model of sepsis. Olaparib pre-treatment significantly improved the survival of septic mice. Pre- and post-treatment with olaparib partially alleviated injury to the lung and kidney. Olaparib treatment also decreased the levels of pro-inflammatory mediators as well as bacterial burden in the serum, peritoneal lavage fluid, and organs. The protective effects of olaparib were associated with suppression of CD14, which activates immune cells. These results suggest a new role for olaparib as a negative regulator of CD14 during organ damage in sepsis.
Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said, “Li and colleagues utilized a mouse model of sepsis and demonstrated that olaparib negatively regulates ERK-mediated CD14 expression, which appears to lead to its efficacy in inhibiting sepsis induced multi-organ injury. ”
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Source: Experimental Biology and Medicine