Abstract 11322: Role of Centhaquine (lyfaquin ® ) in the Protection of Renal Tissues After Acute Kidney Injury

Abstract

Background: Acute Kidney Injury (AKI) is frequently associated with an in-hospital complication of sepsis, heart conditions, hemorrhagic shock, and surgery. However, at present, no specific drug to treat AKI is available. Centhaquine (Lyfaquin ® ) is a safe and effective first-in-class resuscitative agent for hypovolemic shock. We are investigating whether centhaquine could protect kidneys from acute injury during hypovolemic shock. Hypothesis: AKI is known to be associated with shock-related morbidity and mortality. We hypothesize that centhaquine would have a direct effect on alleviating the AKI and reducing shock-related mortality. Methods: Renal arteries of rats were clamped and de-clamped to induce AKI like ischemia/reperfusion model, and hemorrhage was carried out by withdrawing blood for 30 min from the femoral artery. Rats were resuscitated with centhaquine (0.02 mg/kg) for 10 min. Mean Arterial Pressure (MAP), heart rate (HR), and renal blood flow (RBF) were monitored for 120 min. Results: An improved RBF (p<0.003) in centhaquine compared to vehicle rats was observed after resuscitation. While MAP and HR were similar in centhaquine and vehicle groups. At 120 min post-resuscitation, significantly reduced blood lactate level (p=0.0064) in centhaquine than the vehicle was seen. Higher damage in renal tissues in the vehicle than centhaquine was observed by histopathological analysis. Western blots showed higher HIF-1α (p=0.0152) and lower NGAL (p=0.01626) levels in centhaquine vs. vehicle. While significantly higher (p<0.045) expression of HIF-1α and lower expression of Bax (p<0.044) in kidney cortex and medulla of centhaquine rats were observed after immunofluorescence analysis. On the other hand, expression of PHD 3 (p<0.0001) was higher, while the expression of Cytochrome C (p=0.01429) was lower in the cortex of centhaquine than the vehicle. Also, the in situ PCR data showed higher mitochondrial biogenesis in centhaquine than in the vehicle. Conclusions: Centhaquine (Lyfaquin ® ) increases renal blood flow and augments hypoxia response, which probably helps reduce tissue damage and apoptosis following hemorrhagic shock induced AKI, and hence the potential of centhaquine could be explored further to prevent/treat AKI.