ABSTRACT
Vessel allograft preservation is essential for vascular reconstruction surgery. The preservation solution is crucial inextending the preservation period while maintaining vascular endothelial function. Currently, a 0.9% normal salinesolution (NSS) is widely used as a storage solution although its protective effect on endothelial preservation islimited. In this study, we determine the beneficial effect of recombinant human secretory leukocyte protease inhibitor(rhSLPI), supplemented to 0.9% NSS, for isolated aortic preservation. The thoracic and abdominal aorta were isolatedfrom Wistar rats (n = 6), and the aortic rings were subsequently cut and preserved in 0.9% NSS in the presenceand absence of 1 µg/ml rhSLPI for 0, 6, 24, and 48 hours. The preservative solution was collected to determine thereleased lactate dehydrogenase (LDH) activity and pro-inflammatory cytokine levels, including tumor necrosis factorα (TNF-α) and interleukin-6 (IL-6). Furthermore, the appearance and severity of vessel degeneration were subjected toblind histopathological assessment by pathologists. The results indicated that 0.9% NSS, supplemented with rhSLPI,significantly reduced the released LDH activity, TNF-α, and IL-6 levels and could attenuate endothelial detachment,endothelial degeneration, and endothelial necrosis. This study demonstrated for the first time that adding rhSLPI to asaline preservative solution could prevent vascular injury and possibly extend the graft storage duration before clinicalintervention.
ABSTRACT
Hyperglycemia enhances bone resorption and impairment. Controlling blood glucose via metformin benefits bonecells. Hyperglycemia enhances basal phosphorylation of p38 mitogen-activated protein kinase (MAPK), whichaggravates bone resorption. Therefore, the aim of this study was to assess the osteoprotective effects of metformin andp38 MAPK inhibitor in non-obese T2DM rats. In this study, non-obese T2DM (Goto-kakizaki, GK) rats were dividedinto four groups, including DM group, metformin treatment, SB203580 treatment, and metformin combined withSB203580. Wistar rats were used as control group. Femur, tibia, and iliac rat bones were collected to determine boneporosity via synchrotron radiation microtomography. Primary osteoblasts were isolated from calvaria to investigatecell proliferation and osteoblast function, including alkaline phosphatase (ALP) expression and calcium deposition.The results showed that diabetes increase bone porosity. Treatment with metformin significantly reduced porosity intrabecular and cortical bone of the femur, tibia, and iliac, while SB203580 significantly reduced porosity in corticalbone. A combination group showed significantly reduced bone porosity only in trabecular bone of the femur. Isolatedosteoblasts showed lower growth rates. Treatment with metformin significantly increased cell proliferation, ALPexpression, and calcium deposition. In summary, metformin treatment improved bone quality by reducing boneporosity, increasing cell proliferation, and improving osteoblast characteristics.
ABSTRACT
Diabetic complications caused by hyperglycemia and oxidative stress, which can activate p38 mitogen-activatedprotein kinase (p38 MAPK), and aggravate complications via the enhancement of reactive oxygen species (ROS)generation. Recently, metformin or p38 MAPK inhibitors could reduce ROS production in particularly proteincarbonylation, in diabetic vessel. However, the combinatorial effect of metformin and SB203580 on internal organoxidative stress in non-obese (lean) type 2 diabetes mellitus (T2DM) is still uncleared. In this study, Goto-Kakizakirats were divided into four groups, including control diabetic group, metformin-treated group, p38 MAPK inhibitor(SB203580)-treated group, and combination between metformin and p38 MAPK inhibitor (SB203580). Internal organprotein from kidney, pancreas, liver, and brain was determined for protein carbonyl (PC) content by spectrophotometric2, 4-Dinitrophenylhydrazine assay. There was an increase in PC content levels in the serum and internal organs ofT2DM. Metformin ameliorated PC content in serum and internal organs. However, SB203580 could only reduce thePC content in the liver. The combination of metformin and SB203580 could synergistically reduce the PC contentlevels in serum but not the internal organs. In summary, metformin provided the greatest potential for reducingoxidative stress, while SB203580 or combined metformin with SB203580 could not reduce oxidative stress in theinternal organs of non-obese type 2 diabetic rats.
ABSTRACT
Diabetic complications may in part be due to inflammation. Diabetes can also develop in non-obese people.Nonetheless, organ inflammation in non-obese type 2 diabetes mellitus animals has never been investigated. The GotoKakizaki rats were divided into two groups: diabetes and diabetes treated with metformin. The glycemia parameterswere then determined. Serum and internal organs, including the liver, kidney, and brain were collected to determinethe levels of inflammatory cytokine and mRNA expression. The research found an increase in interleukin-6 (IL-6)and IL-1β cytokine levels in the liver of the diabetic group, which corresponds with the mRNA expression of bothcytokines. The metformin group significantly reduces the mRNA expression of liver IL-6. In the kidney, there was anincrease in IL-6 cytokine levels in the diabetic group, while the metformin group could reduce the mRNA expressionlevel of tumor necrosis factor α (TNF-α). In addition, there were IL-6 and TNF-α cytokines level increased in thebrain of the diabetic group. IL-1β mRNA expression levels increased in the diabetic group and were reduced by themetformin treatment. The metformin treatment reduced serum TNF-α cytokines. In summary, this study demonstratedthat internal organ inflammation in non-obese diabetic rats, which could provide evidence for organ inflammation,may potentially explain diabetic complications.
ABSTRACT
Diabetic complications may in part be due to inflammation. Diabetes can also develop in non-obese people.Nonetheless, organ inflammation in non-obese type 2 diabetes mellitus animals has never been investigated. The GotoKakizaki rats were divided into two groups: diabetes and diabetes treated with metformin. The glycemia parameterswere then determined. Serum and internal organs, including the liver, kidney, and brain were collected to determinethe levels of inflammatory cytokine and mRNA expression. The research found an increase in interleukin-6 (IL-6)and IL-1β cytokine levels in the liver of the diabetic group, which corresponds with the mRNA expression of bothcytokines. The metformin group significantly reduces the mRNA expression of liver IL-6. In the kidney, there was anincrease in IL-6 cytokine levels in the diabetic group, while the metformin group could reduce the mRNA expressionlevel of tumor necrosis factor α (TNF-α). In addition, there were IL-6 and TNF-α cytokines level increased in thebrain of the diabetic group. IL-1β mRNA expression levels increased in the diabetic group and were reduced by themetformin treatment. The metformin treatment reduced serum TNF-α cytokines. In summary, this study demonstratedthat internal organ inflammation in non-obese diabetic rats, which could provide evidence for organ inflammation,may potentially explain diabetic complications.
ABSTRACT
Aquilaria crassna has been traditionally used in traditional Thai herbal formulation for treatment of fainting by targeting the cardiovascular system. This study was aimed to investigate the ex vivo effect of ethyl acetate extract of Aquilaria crassna (A.E) in isolated mouse heart, subjected to ischemia/reperfusion, and its mechanism on p38 MAPK activation. The hearts from ICR mouse, age 6-8 weeks, were retrograde-perfused on Langendorff perfusion system. The hearts were randomized to 5-mg/ml A.E for 30 min prior to 30 min of global ischemia, followed by 2 h of reperfusion. After reperfusion, all hearts were stained with 1% triphenyltetrazolium chloride (TTC) and sliced. The TTC-negative infarction volume was expressed as a percentage of heart volume. The p38-MAPK activation was performed by Western blot analysis. The results showed that global ischemia was significantly increased the infarct volume. Pre-treatment with 5-mg/ml of A.E. for 30 min prior to global ischemia significantly reduced infarct volume (47.61±3.68 % versus 21.08± 8.16 %, p < 0.01). In addition, ischemia-induced p38 MAPK phosphorylation was inhibited by pre-treatment with 5-mg/ml of A.E. In conclusion, the ethyl acetate extract of Aquilaria crassna could protect the heart from myocardial ischemia/reperfusion injury by, at least in part, attenuating p38 MAPK phosphorylation.