Abstract:
BACKGROUND:RRx-001 is an anti-cancer immunotherapeutic that increases the sensitivity of drug resistant tumors via multiple mechanisms which involve binding to hemoglobin and enhancing nitrite reductase activity of deoxyhemoglobin. OBJECTIVE:In the present study, the effect of clinically used doses of RRx-001 on erythrocyte deformability was examined. METHODS:A dose dependent effect of RRx-001 (1-1000 micro molar) on erythrocyte deformability was measured by ektacytometer under hypoxia (n = 8). Low dose RRx-001 (20 micro molar) in the presence of ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one), L-NAME (L-NG-Nitroarginine methyl ester) or nitrite were examined both in normoxia and hypoxia. Intracellular nitric oxide (NO) levels were measured fluorometrically with DAF-FM-DA. RESULTS:Higher doses of RRx-001 (100, 1000 micro molar) significantly decreased erythrocyte deformability under hypoxia (p < 0.01; p < 0.05, respectively). RRx-001 (20 micro molar), alone or in combination with ODQ or L-NAME, did not change deformability. However, RRx-001 and nitrite caused an increase in deformability (p < 0.01) under hypoxia. RRx-001 induced NO production was more pronounced in the presence of nitrite (p < 0.05). CONCLUSIONS:Co-administration of RRx-001 and nitrite under hypoxic conditions results in a significant increase in erythrocyte deformability that is related to increased NO production. We suggest that measurement of serum nitrite level in RRx-001 treated cancer patients should be routinely undertaken and supplemented if levels are low for maximal activity.
journal_name
Biorheologyjournal_title
Biorheologyauthors
Cirrik S,Ugurel E,Aksu AC,Oronsky B,Cabrales P,Yalcin Odoi
10.3233/BIR-190213subject
Has Abstractpub_date
2019-01-01 00:00:00pages
221-235issue
4eissn
0006-355Xissn
1878-5034pii
BIR190213journal_volume
56pub_type
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