By Kathy Keatley Garvey
Newly published research by an international team of scientists, headed by the Jun-Yan Liu lab of Tongji University, Shanghai, China, and Bruce Hammock’s lab at UC Davis gives insight into how fish oils may be protective or harmful in animal models of acute kidney injury. This knowledge may provide promising therapeutic strategies for those suffering from acute kidney injury, formerly called acute renal failure.
Acute kidney injury is common in hospitalized patients, especially older adults in intensive care. It occurs when the kidneys suddenly fail to filter waste products from the blood. Many of these patients do not recover requiring dialysis or transplantation, or partly recover and are thus at risk for worsening kidney disease. The condition has a mortality rate of about 50 percent.
The paper, published Nov. 6 in the Proceedings of the National Academy of Sciences, found that a small molecule inhibitor of soluble epoxide hydrolase developed in the Hammock lab at UC Davis helped alleviate acute kidney injury in mice and prolonged their lives.
“The soluble epoxide hydrolase or sEH degrades chemically stable fatty acid epoxides,” said Hammock, a UC Davis distinguished professor who holds a joint appointment in the Department of Entomology and Nematology and at the UC Davis Comprehensive Cancer Center.
“But sometimes it can be useful to block the function of sEH, so that beneficial fatty acid epoxides, like those from omega-3 and omega-6 fatty acids, are not degraded. These fatty acid epoxides have been found to protect the kidney, reduce inflammation, inflammatory pain, and even chronic or neuropathic pain.”
Varying Effects of Oil Metabolites
The team found mixed results when they different compounds derived from fish oils in mice.
“We found that epoxides of docosahexaenoic acid (DHA) and DHA-enriched fish oil worsened kidney injury prophylactically and therapeutically in multiple animal models of acute kidney injury,” said Jun-Yan Liu, who was formerly a postgraduate researcher and assistant project scientist in Hammock’s lab. Fish oil has proven beneficial in other investigations, he said.
Kidney injury expert Alan Parrish of the University of Missouri’s School of Medicine, Columbia, also not involved in the research, called the findings “significant.”
“These results are significant in that they provide a unique mechanistic insight into pathways targeted by soluble epoxide hydrolase inhibitors that attenuate acute kidney injury, providing a powerful rationale for future clinical trials,” he said.
The paper is the work of scientists led by Jun-Yan Liu from the Center for the Nephrology and Metabolomics and Division of Nephrology and Rheumatology, Tongji University School of Medicine, Shanghai, China: Bing-Qing Deng, Ying Luo, Xin Kang, Chang-Bin Li, Jian Huang, Da-Yong Hu, Ming-Yu Wu, and Ai Peng; and Hammock and his lab researchers Jun Yang, Christophe Morrisseau, Kin Sing Stephen Lee at UC Davis.
The work was supported by grants from the National Natural Science Foundation of China, the National Institute for Environmental Health Sciences (NIH) and the National Heart, Lung and Blood Institute (NIH).
Kathy Keatley Garvey writes for the UC Davis Department of Entomology and Nematology and UC Division of Ag and Natural Resources. For more news, follow her Bug Squad blog.