The Efficacy of Cinnamon Extract ( Cinnamomum burmannii ) on Reducing Staging Acute Kidney Injury in Ischemia Reperfusion (IR) Model

Introduction. Acute kidney injury (AKI) is defined as sudden decline in the glomerular filtration rate, resulting in the retention of nitrogenous wastes, such as urea and creatinine in plasma. Cinnamomum burmannii is known as a anti inflammatory renoprotective agent, although the precise mechanism is not well understood. This study aimed to elucidate the effectiveness of Cinnamomum burmannii extract in decreasing creatinine level of acute kidney injury Ischemia reperfusion (IR) model. Method. We performed Ischemia reperfusion (IR) in male Wistar rat to induce acute kidney injury. The rat (n=30) were divided into six groups: IR, 1 group treated with methylprednisolone as a control (IR+M), 3 groups treated with different oral Cinnamomum burmannii extract doses (50mg/kg (IR+EKM1), 100mg/kg (IR+EKM2), and 200 mg/kg (IR+EKM3), and a Sham operation (SO) group. AKI stage reduction based on serum creatinine levels, before and after modeling, before and after the cinnamon extract intervention. Creatinine levels were quntified by spectrophotometry and analyzed by SPSS. Result. Cinnamomum burmannii extract lowers creatinine levels; significant (P <0.05). 200 mg / kgbb is the effective dose of lowering creatinine levels in the IR model. Conclusion. Cinnamomum burmannii extract reduced serum creatinine levels associated with decreased acute renal staging in the IR model.


Introduction
Acute Kidney Injury (AKI) can be defined as a decrease in quickly and suddenly the kidney filtration function. This situation is characterized by an increase in creatinine concentration. The Acute Kidney Injury Network (AKIN) criteria define AKI as "an abrupt reduction in kidney function within 48 hours, currently defined as an absolute increase in serum creatinine of either ≥ 0.3 mg/dL (≥ 26.4 mmol/L), a percentage increase of ≥ 50% (1.5 fold from baseline), or a reduction in urine output (documented oliguria of < 0.5 mL/kg/hour for > 6 hours)". The increase in the incidence of AKI is associated with an increase in the sensitivity of the AKI diagnostic criteria. Several reports in the world show that the incidence varies between 5%-20% in the community, 20% to 50%% in hospitalized patients, to 20% in patients admitted to the intensive care unit (ICU), with reported mortality rates from around the world range from 25% to 80%. Epidemiologic studies have demonstrated that AKI frequently develops into chronic kidney disease and is a major risk factor of end-stage renal disease. [1][2][3][4][5] Ischemia/reperfusion injury (IR) is defined by restriction of blood supply to an organ followed by restoration of blood flow and re -oxygenation. IR contributes to pathological conditions called acute kidney injury (AKI) that is a clinical syndrome with rapid kidney dysfunction and high mortality rates. The pathophysiology of IR in kidney is very complex but some pathological pathways such as activation of neutrophils, release of reactive oxygen species (ROS)  Rat were terminated at day14 after the operation.

Creatinine Analysis by spectrophotometry
The blood of the rat was taken by cutting the neck vein and then collected it in a test tube. Let the blood rest for 15 minutes, then centrifug the blood for 10 minutes at a speed of 3000 rpm to obtain serum. As much as 0.5 mL of pipetized serum is put into a test tube then mixed with 1 mL of working reagent solution.
Measurements were made using a UV spectrophotometer (Microlab 200) at a wavelength of 505 nm, in order to obtain serum creatinine levels. The absorbance measurement of the sample was carried out in the first minute after mixing to obtain AS1. The measurement was then continued after 2 minutes from the first measurement in order to obtain AS2.
Absorbance measurements were carried out in the same way for standard solutions to obtain Ast1 and Ast2.

Results
The probability value for the cinnamon extract group at all doses was <0.05, this indicates that there were differences in the mean creatinine levels in the cinnamon extract group at the dose of 50mg/kg, 100mg/kg and 200mg/kg which also showed the decrease in creatinine level at three doses. The highest decrease of creatinine was found in cinnamon extract 200mg/kg, so it could be stated that the group that was most effective in reducing creatinine level was the group of rat that were given 200 mg / kgBB Cinnamomum burmannii extract.
The mean serum creatinine of rats before IR treatment was 0.37 mg / dl. The creatinine level in the blood increased by 2.73 mg / dl after IR. Based on KDIGO criteria, the increase in serum creatinine indicates a stage 2 acute kidney injury. After being given Cinnamomum burmannii extract, the serum cretainine level in rats was 0.62 mg/dl , which means that there is a decrease in AKI, from stage 2 to stage 1.  Creatinin level creatinine excretion so that creatinine levels in the blood will decrease. [15][16] The use of medicinal plants is effective because it has low side effects compared to modern medicines.

Conclusion
This study showed the beneficial effect of Cinnamomum burmanii supplementation in acute kidney injury conditions through reduction of creatinine level . Following study about adding Cinnamomum burmanii supplementary therapy to AKI ambulatory therapy will be needed to adjust those effects in clinical use. We also need further study to understand the precise mechanism of Cinnamomum burmanii in both the classical and non-classical pathways in reactive oxygen species (ROS) cause oxidative stress and other potential cells of renal injury.