Protective effect of anisodamine in rats with glycerol-induced acute kidney injury.

BACKGROUND: Anisodamine is used for the treatment of reperfusion injury in various organs. In this study, we investigated the effectiveness and mechanisms of action of anisodamine in promoting recovery from glycerol-induced acute kidney injury (AKI). METHODS: We compared the protective effects of atropine and anisodamine in the rat model of glycerol-induced AKI. We examined signaling pathways involved in oxidative stress, inflammation and apoptosis, as well as expression of kidney injury molecule-1 (KIM-1). Renal injury was assessed by measuring serum creatinine and urea, and by histologic analysis. Rhabdomyolysis was evaluated by measuring creatine kinase levels, and oxidative stress was assessed by measuring malondialdehyde (MDA) and superoxide dismutase (SOD) levels in kidney tissues. Inflammation was assessed by quantifying interleukin 6 (IL-6) and CD45 expression. Apoptosis and necrosis were evaluated by measuring caspase-3 (including cleaved caspase 3) and RIP3 levels, respectively. RESULTS: Glycerol administration resulted in a higher mean histologic damage score, as well as increases in serum creatinine, urea, creatine kinase, reactive oxygen species (ROS), MDA, IL-6, caspase-3 and KIM-1 levels. Furthermore, glycerol reduced kidney tissue SOD activity. All of these markers were significantly improved by anisodamine and atropine. However, the mean histologic damage score and levels of urea, serum creatinine, creatine kinase, ROS and IL-6 were lower in the anisodamine treatment group compared with the atropine treatment group. CONCLUSION: Pretreatment with anisodamine ameliorates renal dysfunction in the rat model of glycerol-induced rhabdomyolytic kidney injury by reducing oxidative stress, the inflammatory response and cell death.

Evaluating the expression of CARMA3 as a prognostic tumor marker in renal cell carcinoma.

Increased expression of CARMA3 has been reported to be involved in tumorigenesis and tumor progression of several cancer types. The aim of our study is to investigate the prognostic role of CARMA3 expression in patients with renal cell carcinoma (RCC). Real-time quantitative PCR was performed to detect CARMA3 mRNA expression level in 31 paired samples of RCC and adjacent noncancerous renal tissues. Subsequently, extensive immunohistochemistry was performed to detect CARMA3 protein expression in 114 RCC cases. Clinicopathological data for these patients were evaluated. The prognostic significance was assessed using the Kaplan-Meier survival estimates and log-rank tests. CARMA3 mRNA expression was significantly higher in RCC tissues compared with adjacent noncancerous renal tissues (3.525 ± 1.233 vs. 1.512 ± 0.784, P < 0.001). In addition, high CARMA3 expression in RCC tissues was significantly associated with tumor size (P = 0.026), histological differentiation (P = 0.039), tumor stage (P = 0.006), and the presence of metastasis (P < 0.001). Moreover, Kaplan-Meier analysis showed that patients with high CARMA3 expression also had a significantly poorer prognosis than those with low CARMA3 expression (log-rank test, P < 0.001). Furthermore, multivariate analysis illustrated that CARMA3 overexpression might be an independent prognostic indicator for the survival of patients with RCC. In conclusion, this work shows that CARMA3 may serve as a novel and prognostic marker for RCC and play a role during the development and progression of the disease.

[Effects of fluvastatin on the activation of p38 mitogen-activated protein kinase in glomerular mesangial cells under high concentration of glucose].

This study is to investigate the effects of fluvastatin on the activation of p38 mitogen-activated protein kinase (p38 MAPK) and cAMP response element-binding protein (CREB1) in glomerular mesangial cells under high concentration of glucose. High concentration glucose and fluvastatin were used to stimulate the cultured rat glomerular mesangial cells (GMCs) in vitro. The protein expressions of p38 MAPK, CREB1, p-p38 MAPK and p-CREB1 were observed with Western blotting. TGF-beta1 and fibronectin (FN) mRNA were measured with reverse transcription and polymerase chain reaction (RT-PCR). The protein synthesis of laminine (LN) and type IV collagen in the supernatants of the GMCs were detected with radioimmunoassay. Compared with low glucose control group, the expressions of p-p38 MAPK, p-CREB1 were increased obviously in high glucose group, TGF-beta1 mRNA and FN mRNA, LN and type IV collagen in the supernatants were increased significantly in GMCs under high concentration glucose medium. The expression levels of p-p38 MAPK, p-CREB1, TGF-beta1 mRNA, and FN mRNA, LN and type IV collagen in the supernatants were significantly lower in the fluvastatin group than those in the high concentration glucose group. It is concluded that fluvastatin can inhibit over production of TGF-beta1 and ECM proteins in GMCs under high concentration of glucose, partly by regulating the phosphorylation of p38 MAPK and CREB1.

Neuroprotective effects of sevoflurane against electromagnetic pulse-induced brain injury through inhibition of neuronal oxidative stress and apoptosis.

Electromagnetic pulse (EMP) causes central nervous system damage and neurobehavioral disorders, and sevoflurane protects the brain from ischemic injury. We investigated the effects of sevoflurane on EMP-induced brain injury. Rats were exposed to EMP and immediately treated with sevoflurane. The protective effects of sevoflurane were assessed by Nissl staining, Fluoro-Jade C staining and electron microscopy. The neurobehavioral effects were assessed using the open-field test and the Morris water maze. Finally, primary cerebral cortical neurons were exposed to EMP and incubated with different concentration of sevoflurane. The cellular viability, lactate dehydrogenase (LDH) release, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were assayed. TUNEL staining was performed, and the expression of apoptotic markers was determined. The cerebral cortexes of EMP-exposed rats presented neuronal abnormalities. Sevoflurane alleviated these effects, as well as the learning and memory deficits caused by EMP exposure. In vitro, cell viability was reduced and LDH release was increased after EMP exposure; treatment with sevoflurane ameliorated these effects. Additionally, sevoflurane increased SOD activity, decreased MDA levels and alleviated neuronal apoptosis by regulating the expression of cleaved caspase-3, Bax and Bcl-2. These findings demonstrate that Sevoflurane conferred neuroprotective effects against EMP radiation-induced brain damage by inhibiting neuronal oxidative stress and apoptosis.

Prevalence, awareness, treatment, and control of hypertension in the non-dialysis chronic kidney disease patients.

BACKGROUND: Data on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China. METHODS: The survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients. RESULTS: The analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05). CONCLUSIONS: The prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.