The Therapeutic Effects of Curcumin in Early Septic Acute Kidney Injury: An Experimental Study.

PURPOSE: Sepsis is the leading condition associated with acute kidney injury (AKI) in the hospital and intensive care unit (ICU), sepsis-induced AKI (S-AKI) is strongly associated with poor clinical outcomes. Curcumin possesses an ability to ameliorate renal injury from ischemia-reperfusion, but it is still unknown whether they have the ability to reduce S-AKI. The aim of this study was to investigate the protective effects of curcumin on S-AKI and to assess its therapeutic potential on renal function, inflammatory response, and microcirculatory perfusion. METHODS: Male Sprague-Dawley (SD) rats underwent cecal ligation and puncture (CLP) to induce S-AKI and immediately received vehicle (CLP group) or curcumin (CLP+Cur group) after surgery. At 12 and 24h after surgery, serum indexes, inflammatory factors, cardiac output (CO), renal blood flow and microcirculatory flow were measured. RESULTS: Serum levels of creatinine (Scr), cystatin C (CysC), IL-6 and TNF-α were significantly lower in the CLP+Cur group than those in the CLP group (P < 0.05). Treatment with curcumin improved renal microcirculation at 24h by measurement of contrast enhanced ultrasound (CEUS) quantitative parameters [peak intensity (PI); half of descending time (DT/2); area under curve (AUC); P < 0.05]. In histopathological analysis, treatment with curcumin reduced damage caused by CLP. CONCLUSION: Curcumin can alleviate S-AKI in rats by improving renal microcirculatory perfusion and reducing inflammatory response. Curcumin may be a potential novel therapeutic agent for the prevention or reduction of S-AKI.

[Chrysin inhibited epithelial-mesenchymal transition of type â ¡ alveolar epithelial cell by regulating NF-κB/Twist 1 signaling pathway].

This study aimed to assess whether chrysin(ChR) can inhibit epithelial-mesenchymal transition(EMT) of type Ⅱ alveolar epithelial cell and produce anti-pulmonary fibrosis effect by regulating the NF-κB/Twist 1 signaling pathway. Sixty rats were randomly divided into the control group, the bleomycin(BLC) group, BLC+ChR(50 mg·kg~(-1)) group and BLC+ChR(100 mg·kg~(-1)) group, with 15 rats in each group. The pulmonary fibrosis model was induced by intratracheal injection of BLC(7 500 U·kg~(-1)). Rats were orally administered with different doses of ChR after BLC injection for 28 days. The cells were divided into control group, TGF-ß1 group(5 ng·mL~(-1)), and TGF-ß1+ChR(1, 10, 100 µmol·L~(-1)) groups. The type Ⅱ alveolar epithelial cells were treated with TGF-ß1 for 24 h, and then treated with TGF-ß1 for 48 h in the presence or absence of different doses of ChR(1, 10 and 100 µmol·L~(-1)). The morphological changes and collagen deposition in lung tissues were analyzed by HE staining, Masson staining and immunohistochemistry. The mRNA and protein expression levels of collagen Ⅰ, E-cadherin, zonula occludens-1(ZO-1), vimentin, alpha smooth muscle actin(α-SMA), inhibitor of nuclear factor kappa B alpha(IκBα), nuclear factor-kappa B p65(NF-κB p65), phospho-NF-κB p65(p-p65) and Twist 1 in lung tissues and cells were detected by qPCR and Western blot, respectively. The animal experiment results showed that as compared with the BLC group, after administration of ChR for 28 days, bleomycin-induced pulmonary fibrosis in rats was significantly relieved, collagen Ⅰ expression in lung tissues was significantly reduced(P<0.05 or P<0.01), and EMT of alveolar epithelial cells was obviously inhibited [the expression levels of E-cadherin and ZO-1 were increased and the expression levels of vimentin and α-SMA were decreased(P<0.05 or P<0.01)], concomitantly with significantly reduced IκBα and p65 phosphorylation level in cytoplasm and decreased NF-κB p65 and Twist 1 expression in nucleus(P<0.05 or P<0.01). The cell experiment results showed that different doses of ChR(1, 10 and 100 µmol·L~(-1)) significantly reduced TGF-ß1-induced collagen Ⅰ expression(P<0.05 or P<0.01), significantly inhibited EMT of type Ⅱ alveolar epithelial cells[the expression levels of E-cadherin and ZO-1 were increased and the expression levels of vimentin and α-SMA were decreased(P<0.05 or P<0.01)], and inhibited IκBα and p65 phosphorylation in cytoplasm and down-regulated NF-κB p65 and Twist 1 expression in nucleus induced by TGF-ß1(P<0.05 or P<0.01). The results suggest that ChR can reverse EMT of type Ⅱ alveolar epithelial cell and alleviate pulmonary fibrosis in rats, and its mechanism may be associated with reducing IκBα phosphorylation and inhibiting NF-κB p65 phosphorylation and nuclear transfer, thus down-regulating Twist 1 expression.

Ischemic or toxic injury: A challenging diagnosis and treatment of drug-induced stenosis of the sigmoid colon.

A 48-year-old woman was admitted with 15-mo history of abdominal pain, diarrhea and hematochezia, and 5-mo history of defecation difficulty. She had been successively admitted to nine hospitals, with an initial diagnosis of inflammatory bowel disease with stenotic sigmoid colon. Findings from computed tomography virtual colonoscopy, radiography with meglumine diatrizoate, endoscopic balloon dilatation, metallic stent implantation and later overall colonoscopy, coupled with the newfound knowledge of compound Qingdai pill-taking, led to a subsequent diagnosis of ischemic or toxic bowel disease with sigmoid colon stenosis. The patient was successfully treated by laparoscopic sigmoid colectomy, and postoperative pathological examination revealed ischemic or toxic injury of the sigmoid colon, providing a final diagnosis of drug-induced sigmoid colon stenosis. This case highlights that adequate awareness of drug-induced colon stenosis has a decisive role in avoiding misdiagnosis and mistreatment. The diagnostic and therapeutic experiences learnt from this case suggest that endoscopic balloon expansion and colonic metallic stent implantation as bridge treatments were demonstrated as crucial for the differential diagnosis of benign colonic stenosis. Skillful surgical technique and appropriate perioperative management helped to ensure the safety of our patient in subsequent surgery after long-term use of glucocorticoids.