Carbon monoxide: An emerging therapy for acute kidney injury

Abstract

Treating acute kidney injury (AKI) represents an important unmet medical need both in terms of the seriousness of this medical problem and the number of patients. There is also a large untapped market opportunity in treating AKI. Over the years, there has been much effort in search of therapeutics with minimal success. However, over the same time period, new understanding of the underlying pathobiology and molecular mechanisms of kidney injury have undoubtedly helped the search for new therapeutics. Along this line, carbon monoxide (CO) has emerged as a promising therapeutic agent because of its demonstrated cytoprotective, and immunomodulatory effects. CO has also been shown to sensitize cancer, but not normal cells, to chemotherapy. This is particularly important in treating cisplatin-This is the author manuscript accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

PSTPIP2 inhibits cisplatin-induced acute kidney injury by suppressing apoptosis of renal tubular epithelial cells

“…Cisplatin is an effective chemotherapeutic agent used to treat a wide variety of solid tumours. However, cisplatin damages the kidney, and there is no available treatment to prevent nephrotoxicity of cisplatin [24][25][26] . A combination of cisplatin with HDAC inhibitors has been tested in several chemotherapy-resistant cancers to enhance the efficacy of cisplatin [27][28][29][30] .…”

Adapting decarbonylation chemistry for the development of prodrugs capable of in vivo delivery of carbon monoxide utilizing sweeteners as carrier molecules

“…With the firm establishment of carbon monoxide (CO) as an endogenous signaling molecule, there has been an increasing level of interest in developing CO-based therapeutics by taking advantage of its demonstrated cyto-and organ-protective effects. [1][2][3] Along this line, the organ protective effects of CO have been demonstrated in injury models of kidney, 4,5 lungs, 6 gastrointestinal tract, 7,8 liver, 9 among others. Because of the gaseous nature of CO, the difficulty in delivering a gas as a therapeutic to patients, and the potential risks it poses to healthcare workers as well as patients in terms of accidental poisoning, there have been intense efforts in developing alternative delivery forms.…”

Therapeutic Potential of Heme Oxygenase-1 and Carbon Monoxide in Acute Organ Injury, Critical Illness, and Inflammatory Disorders

“…CO improved pulmonary vein pO 2 in the graft after transplantation, and significantly inhibited neutrophil migration into the graft, and preserved lung ultrastructure [ 106 ]. Low concentration CO has been found to exert protective effects in IRI associated with transplantation of other organs, including kidney [ 108 , 109 , 110 , 144 ], as well as liver, pancreas and intestine, as described elsewhere [ 111 ]. In pigs, CO derived from CORM-3 mitigated skeletal muscle IRI associated with acute compartment syndrome [ 122 ].…”