Obese Zucker rats are susceptible to increased hepatic ischemia/reperfusion (I/RP) injury. Increased lipid peroxidation occurs in this model with warm ischemia. We hypothesized that a severe depletion of phospholipids (PL) occurs with warm I/RP in fatty livers. Obese (Ob) and lean (Ln) Zucker rats were subjected to 90 min of in vivo partial hepatic warm I followed by RP. Total lipids extracted from one gm of liver (median lobe) taken at the end of 1, 2 and 6 hr of RP and sham (Sh) surgery (n=5 Ln & Ob) were analyzed by 202.3 MHz 31P NMR, which provided good resolution of individual PL. Obese (Sh) rats contained 22% more PL than Ln (P= < 0.01). Ischemia caused similar decreases in PL in both Ob (to 67% Sh) and Ln rats (62%). Following 2 hr RP, PL in Ob rats decreased further (46% Sh) and recovered only marginally at 6 hr (53%), in marked contrast to the rapid recovery in Ln to preischemic levels (110% Sh at both 2 and 6 hr; P=<0.001). Mole percents of individual PL did not change significantly except for lysophosphatidylcholine, which increased from 0.43 to 1.3% (Sh vs. 6 hr RP) in the Ob, but decreased from 0.98 to 0.52% in Ln animals (P = <0.001). Fatty livers thus are more vulnerable to phospholipid depletion in response to warm ischemia/reperfusion than normal livers.
Theopioid epidemic is a rapidly growing crisis around the world. Current models forpharmacokinetic assessment of countermeasures use African green monkeys (AGM). Arapid, sensitive and selective method was developed and validated usingLC‐MS/MS for the determination of naloxone and 6α‐naloxol in AGM plasma. Samplepreparation involved a simple solid phase extraction (SPE) using ahydrophilic‐lipophilic‐balanced reversed‐phase cartridge. Separation of naloxoneand 6α‐naloxol was achieved on a Halo C18, 2.1 × 50 mm, 2.7μ analytical columnusing an Agilent 1290 Infinity HPLC. A solvent system of methanol‐water‐formicacid was used for the elution of analytes. The analytes were detected and monitoredby a SCIEX QTRAP 6500+ triple quadrupole tandem mass spectrometer operatedin electrospray ionization (ESI) positive mode and multiple reaction monitoring(MRM). Molecular ion transitions for naloxone, 6α‐naloxol and naloxone‐D5 were 328.0/212.0,330.0/185.0, and 333.1/212.0 m/z, respectively. The method was validated usingcalibration and recovery assays with spiked samples. Linear calibration curveswere generated over the range of 1.5–100 ng/ml with values for the coefficientof determination (R2) of >0.9950. The values for both inter‐dayand intra‐day precision and accuracy were well within the generally acceptedcriteria for analytical methods (≤15%). This method was subsequentlyused to measure plasma concentrations of naloxone and 6α‐naloxol in male AGMs administerednaloxone subcutaneously and intravenously. The developed method demonstratedexcellent recovery, repeatability, accuracy and sensitivity.Support or Funding InformationDISCLAIMERS. The views expressed in this abstractare those of the authors (s) and do not reflect the official policy of theDepartment of Army, Department of Defense, or U. S. Government. This researchwas supported by the Defense Threat Reduction Agency – Joint Science andTechnology office, Medical S&T Division.Thisproject was supported in part by an appointment to the Research ParticipationProgram for the U.S. Army Medical Research and Materiel Command administratedby the Oak Ridge Institute for Science and Education through an agreementbetween the U.S. Army Medical Research and Materiel Command.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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