Vildagliptin Treatment Ameliorates Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction.

Renal interstitial fibrosis in mice can be modeled using unilateral ureteral obstruction (UUO). Here, we investigated the anti-fibrotic effects of the dipeptidyl peptidase-4 inhibitor vildagliptin in this model. We found that vildagliptin given in the drinking water at 10.

Prevention of Renal Interstitial Fibrosis by Suplatast in a Mouse Model.

Suplatast is a T helper 2 (Th2) cytokine inhibitor. Here, we tested its therapeutic effects using a mouse model of renal interstitial fibrosis caused by unilateral ureteral obstruction (UUO). In this model, suplatast was found to prevent the induced fibrosis in the obstructed kidney when given in the drinking water at 100 mg/kg/d.

Effect of N-Acetyl Cysteine on Renal Interstitial Fibrosis in Mice.

This study examined the effect of N-acetyl cysteine (NAC), a reactive oxygen species (ROS) inhibitor, on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO) in mice. UUO led to a significant increase in the fibrotic area of obstructed kidneys, which was attenuated by NAC (84.8 mg/kg/d) in the drinking water.

Dimethylthiourea ameliorates carbon tetrachloride-induced acute liver injury in ovariectomized mice.

Aims: In order to clarify hepato-protective actions of estrogen, we examined the progress of carbon tetrachloride (CCl)-induced acute liver injury (ALI) in sham and ovariectomized (ovx) mice and the effects of dimethylthiourea (DMTU), a hydroxyl radical scavenger, and meloxicam (Melo), a selective cox-2 inhibitor, on the development of CCl-induced ALI.

Main Methods: Female C57BL/6 J mice weighing 15-20 g were performed sham or ovx operation at 8 weeks of age. Blood and liver samples were collected 15 and 24 h after CCl administration.

Effect of brefelamide on HGF-induced survival of 1321N1 human astrocytoma cells.

Malignant gliomas are characterized by their high level of resistance to chemo- and radiotherapy and new treatment options are urgently required. We previously demonstrated that brefelamide, an aromatic amide isolated from methanol extracts of cellular slime molds Dictyostelium brefeldianum and D. giganteum, had antiproliferative effects on 1321N1 human astrocytoma cells, a model of glioma.

Effect of amlodipine on mouse renal interstitial fibrosis.

Unilateral ureteral obstruction (UUO) is a well-established method to study interstitial fibrosis of the kidney. In this study, we investigated the effects of a calcium channel blocker, amlodipine, on UUO-induced renal interstitial fibrosis in mice. UUO significantly increased the fibrotic area in the obstructed kidney, but this change was inhibited by amlodipine (6.

Apocynin reduced doxycycline-induced acute liver injury in ovariectomized mice.

To determine the physiological role of estrogen in the development of liver injury, we examined the sensitivities of sham and ovariectomy (ovx) mice against doxycycline (DOXY)-induced acute liver injury. Ovx or sham operation was performed in C57BL/6J wild-type female mice of eight weeks of age. Sham mice and ovx mice were treated with DOXY (240 mg/kg ip) 8 weeks after the operation, 30 min after apocynin (5 mg/kg) or saline administration.

Effect of cyclooxygenase (COX)-2 inhibition on mouse renal interstitial fibrosis.

Unilateral ureteral obstruction (UUO) is a well-established model for the study of interstitial fibrosis in the kidney. In this study, we investigated the effects of a COX-2 inhibitor, meloxicam, on UUO-induced renal interstitial fibrosis in mice. Serum creatinine, blood urea nitrogen and urinary glucose were significantly increased by UUO.

Regeneration of injured renal tubules.

Acute kidney injury (AKI), clinically defined by high serum creatinine and low urine flow, has many complicated pathophysiological features including tubular and glomerular injury. Although renal tubules are thought to be constituted by highly differentiated epithelial cells, it is possible to repair injured nephrons by the healing process. Several studies have revealed that AKI, especially AKI caused by ischemia/reperfusion injury or nephrotoxic medication, depends on a number of factors, including activation of transcriptional factors, endothelial injury of peritubular small vessels, immune responses, and inflammatory processes associated with necrosis and apoptosis of renal tubular epithelium.

Amelioration of cisplatin-induced mouse renal lesions by a cyclooxygenase (COX)-2 selective inhibitor.

In this study, we investigated the effects of the cyclooxygenase (COX)-2 selective inhibitor, meloxicam, on cisplatin-induced inflammation, oxidative stress and renal lesions in BALB/c mice. A single cisplatin injection (13 mg/kg, i.p.

Interleukin-6 modulates oxidative stress produced during the development of cisplatin nephrotoxicity.

Aims: We reported that interleukin-6 (IL-6) plays a protective role in the development of cisplatin-induced acute renal failure (ARF) through upregulation of anti-oxidative stress factors. In this study, we examined the effects of dimethylthiourea (DMTU), a hydroxyl radical scavenger, on the development of cisplatin-induced ARF in wild-type (WT) and IL-6(-/-) mice to determine how IL-6 contributes to modulation of oxidative stress caused by cisplatin.

Main Methods: WT and IL-6(-/-) male mice were given either cisplatin (30 mg/kg) or saline intraperitoneally.

Interleukin-6 plays a protective role in development of cisplatin-induced acute renal failure through upregulation of anti-oxidative stress factors.

Aims: Cisplatin, a major chemotherapeutic agent, accumulates in proximal tubules of the kidneys and causes acute renal failure dose-dependently. We previously reported that cisplatin induced more severe renal dysfunction in interleukin-6 (IL-6) knockout (IL-6(-/-)) mice than in wild-type (WT) mice. Expression of a pro-apoptotic protein was significantly increased with cisplatin in IL-6(-/-) mice compared to that in WT mice.

A reduction of epidermal growth factor receptor is involved in brefelamide-induced inhibition of phosphorylation of ERK in human astrocytoma cells.

Brefelamide is an aromatic amide isolated from Dictyostelium cellular slime molds. We found that brefelamide has a potent inhibitory growth effect measured by MTT assay in 1321N1 human astrocytoma cells. The inhibition was associated with reduced phosphorylation of extracellular signal-regulated kinase (ERK).

Distinct effects of z-335, a new thromboxane A2 receptor antagonist, on rabbit platelets and aortic smooth muscle.

The effect of a novel thromboxane A2 receptor (TP) antagonist, (+/-)-sodium[2-(4-chlorophenylsulfonylaminomethyl)- indan-5-yl]acetate monohydrate (Z-335), on the U46619-induced responses was compared between rabbit platelets and aorta. Z-335 inhibited platelet shape change induced by U46619 with higher efficacy than SQ29548, a common TP antagonist. The U46619-induced platelet aggregation was inhibited by Z-335 in a noncompetitive manner, while it was competitively inhibited by SQ29548.

Thromboxane A2 receptor-mediated G12/13-dependent glial morphological change.

Glial cells express thromboxane A(2) receptor, but its physiological role remains unknown. The present study was performed to examine thromboxane A(2) receptor-mediated morphological change in 1321N1 human astrocytoma cells. Thromboxane A(2) receptor agonists U46619 and STA(2) caused a rapid morphological change to spindle shape from stellate form of the cells pretreated with dibutyryl cyclic AMP, but neither carbachol nor histamine caused the change, suggesting that G(q) pathway may not mainly contribute to the change.