Effects of Pentoxifylline on Peritoneal Fibroblasts and Silica-Induced Peritoneal Fibrosis

2003 ◽  
Vol 23 (3) ◽  
pp. 228-236 ◽  
Author(s):  
Cheng-Chung Fang ◽  
Ming-Nan Lai ◽  
Chiang-Ting Chien ◽  
Kuan-Yu Hung ◽  
Chien-Chen Tsai ◽  
...  

♦ Background Peritoneal fibrosis is a long-term complication following continuous ambulatory peritoneal dialysis (CAPD). Peritoneal fibroblasts may play an important role in peritoneal fibrosis. Up to now, the treatment of peritoneal fibrosis in patients with CAPD remains unsatisfactory. Pentoxifylline (PTX) is a xanthine derivative and is used in the treatment of peripheral vascular and cerebrovascular diseases. Several studies have demonstrated that PTX can ameliorate fibrosis of the skin, liver, and kidney. ♦ Objective To investigate the effect of PTX on in vitro growth and collagen synthesis of human peritoneal fibroblasts (HPFBs), and to evaluate the effects of PTX on silica-induced peritoneal fibrosis in vivo. ♦ Design and Measurements In the in vitro study, HPFBs were cultured from human omentum. The effect of PTX on the growth of serum-stimulated HPFBs was evaluated by MTT assay. The effect of PTX on the collagen synthesis of HPFB was measured by [3H]-proline incorporation. Expression of type I and type III collagen mRNA was evaluated by Northern blotting. The effects of PTX on matrix metalloproteinase (MMP) activity and cAMP level in HPFBs were measured by immunoassays. In the in vivo study, Wistar rats were randomly divided into five groups. All rats received intraperitoneal (IP) injection of silica suspension (250 mg/100 g body weight) on day 0. The rats of group 1 (control group) were injected with vehicle IP every day for 14 days. The rats of groups 2, 3, and 4 were injected with PTX (4 mg/100 g body weight) IP every day for 3, 7, and 14 days, respectively. The rats in group 5 received an intravenous infusion of PTX (8 mg/100 g body weight) every day for 7 days. On the 15th day after silica injection, all rats were sacrificed. Their parietal and visceral peritoneums were removed and processed for pathology, and the severity of fibrosis was measured and scored. ♦ Results: In vitro, PTX inhibited serum-stimulated HPFB growth (maximum was 93% at 1 mg PTX/mL) in a dose-dependent manner. Collagen synthesis by HPFB was reduced (47% at 1 mg PTX/mL), and collagen I and III mRNA expression in HPFBs was suppressed by PTX. The PTX did not affect the MMP (including MMP-1, MMP-8, and MMP-13) activities of HPFBs. The mechanism of PTX was through increasing cAMP by its phosphodiesterase inhibiting activity. In vivo, the severity of fibrosis was significantly reduced in groups 4 and 5 compared to group 1 ( p < 0.05). ♦ Conclusion These results suggest that PTX can inhibit growth of and collagen synthesis by HPFBs in vitro. The fibrosis derived from silica-induced peritonitis in vivo was also ameliorated by PTX. Therefore, pentoxifylline may have the potential to be used to treat peritoneal fibrosis in patients on CAPD.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 386
Author(s):  
Tung-Hu Tsai ◽  
Yu-Jen Chen ◽  
Li-Ying Wang ◽  
Chen-Hsi Hsieh

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).


Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 331
Author(s):  
Jung-Yun Lee ◽  
Tae Yang Kim ◽  
Hanna Kang ◽  
Jungbae Oh ◽  
Joo Woong Park ◽  
...  

Excess body weight is a major risk factor for type 2 diabetes (T2D) and associated metabolic complications, and weight loss has been shown to improve glycemic control and decrease morbidity and mortality in T2D patients. Weight-loss strategies using dietary interventions produce a significant decrease in diabetes-related metabolic disturbance. We have previously reported that the supplementation of low molecular chitosan oligosaccharide (GO2KA1) significantly inhibited blood glucose levels in both animals and humans. However, the effect of GO2KA1 on obesity still remains unclear. The aim of the study was to evaluate the anti-obesity effect of GO2KA1 on lipid accumulation and adipogenic gene expression using 3T3-L1 adipocytes in vitro and plasma lipid profiles using a Sprague-Dawley (SD) rat model. Murine 3T3-L1 preadipocytes were stimulated to differentiate under the adipogenic stimulation in the presence and absence of varying concentrations of GO2KA1. Adipocyte differentiation was confirmed by Oil Red O staining of lipids and the expression of adipogenic gene expression. Compared to control group, the cells treated with GO2KA1 significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (CEBP/α). Consistently, the mRNA expression of downstream adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), were significantly lower in the GO2KA1-treated group than in the control group. In vivo, male SD rats were fed a high fat diet (HFD) for 6 weeks to induced obesity, followed by oral administration of GO2KA1 at 0.1 g/kg/body weight or vehicle control in HFD. We assessed body weight, food intake, plasma lipids, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for liver function, and serum level of adiponectin, a marker for obesity-mediated metabolic syndrome. Compared to control group GO2KA1 significantly suppressed body weight gain (185.8 ± 8.8 g vs. 211.6 ± 20.1 g, p < 0.05) with no significant difference in food intake. The serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly lower in the GO2KA1-treated group than in the control group, whereas the high-density lipoprotein (HDL) level was higher in the GO2KA1 group. The GO2KA1-treated group also showed a significant reduction in ALT and AST levels compared to the control. Moreover, serum adiponectin levels were significantly 1.5-folder higher than the control group. These in vivo and in vitro findings suggest that dietary supplementation of GO2KA1 may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.


Pathogens ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 67 ◽  
Author(s):  
Tomoyoshi Doki ◽  
Tomoyo Tarusawa ◽  
Tsutomu Hohdatsu ◽  
Tomomi Takano

Background: The cationic amphiphilic drug U18666A inhibits the proliferation of type I FIPV in vitro. In this study, we evaluated the in vivo antiviral effects of U18666A by administering it to SPF cats challenged with type I FIPV. Methods: Ten SPF cats were randomly assigned to two experimental groups. FIPV KU-2 were inoculated intraperitoneally to cats. The control group was administered PBS, and the U18666A-treated group was administered U18666A subcutaneously at 2.5 mg/kg on day 0, and 1.25 mg/kg on days 2 and 4 after viral inoculation. Results: Two of the five control cats administered PBS alone developed FIP. Four of the five cats administered U18666A developed no signs of FIP. One cat that temporarily developed fever, had no other clinical symptoms, and no gross lesion was noted on an autopsy after the end of the experiment. The FIPV gene was detected intermittently in feces and saliva regardless of the development of FIP or administration of U18666A. Conclusions: When U18666A was administered to cats experimentally infected with type I FIPV, the development of FIP might be suppressed compared with the control group. However, the number of animals with FIP is too low to establish anti-viral effect of U18666A in cats.


Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2600 ◽  
Author(s):  
Luna Ge ◽  
Yazhou Cui ◽  
Kai Cheng ◽  
Jinxiang Han

Isopsoralen (IPRN), one of the main effective ingredients in Psoralea corylifolia Linn, has a variety of biological effects, including antiosteoporotic effects. In vivo studies show that IPRN can increase bone strength and trabecular bone microstructure in a sex hormone deficiency-induced osteoporosis model. However, the mechanism underlying this osteogenic potential has not been investigated in detail. In the present study, we investigated the molecular mechanism of IPRN-induced osteogenesis in MC3T3-E1 cells. Isopsoralen promoted osteoblast differentiation and mineralization, increased calcium nodule levels and alkaline phosphatase (ALP) activity and upregulated osteoblast markers, including ALP, runt-related transcription factor 2 (RUNX2), and collagen type I alpha 1 chain (COL1A1). Furthermore, IPRN limited the nucleocytoplasmic shuttling of aryl hydrocarbon receptor (AhR) by directly binding to AhR. The AhR target gene cytochrome P450 family 1 subfamily A member 1 (CYP1A1) was also inhibited in vitro and in vivo. This effect was inhibited by the AhR agonists indole-3-carbinol (I3C) and 3-methylcholanthrene (3MC). Moreover, IPRN also increased estrogen receptor alpha (ERα) expression in an AhR-dependent manner. Taken together, these results suggest that IPRN acts as an AhR antagonist and promotes osteoblast differentiation via the AhR/ERα axis.


Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 478 ◽  
Author(s):  
Rasha Al-Rikabi ◽  
Hanady Al-Shmgani ◽  
Yaser Hassan Dewir ◽  
Salah El-Hendawy

(1) Background: Plant flavonoids are efficient in preventing and treating various diseases. This study aimed to evaluate the ability of hesperidin, a flavonoid found in citrus fruits, in inhibiting lipopolysaccharide (LPS) induced inflammation, which induced lethal toxicity in vivo, and to evaluate its importance as an antitumor agent in breast cancer. The in vivo experiments revealed the protective effects of hesperidin against the negative LPS effects on the liver and spleen of male mice. (2) Methods: In the liver, the antioxidant activity was measured by estimating the concentration of glutathione (GSH) and catalase (CAT), whereas in spleen, the concentration of cytokines including IL-33 and TNF-α was measured. The in vitro experiments including MTT assay, clonogenity test, and sulforhodamine 101 stain with DAPI (4′, 6-diamidino-2-phenylindole) were used to assess the morphological apoptosis in breast cancer cells. (3) Results: The results of this study revealed a significant increase in the IL-33 and TNF-α cytokine levels in LPS challenged mice along with a considerable elevation in glutathione (GSH); moreover, the catalase (CAT) level was higher compared to that of the control group. Cytotoxicity of the MCF-7 cell line revealed significant differences among the groups treated with different concentrations when compared to the control groups, in a concentration-dependent manner. Hesperidin significantly inhibited the colony formation of MCF7 cells when compared to that of control. Clear changes were observed in the cell shape, including cell shrinkage and chromatin condensation, which were associated with a later apoptotic stage. (4) Conclusion: The results indicate that hesperidin might be a potential candidate in preventing diseases.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5053-5053
Author(s):  
Jian Da Hu ◽  
Yi Huang ◽  
Yingyu Chen ◽  
Tiannan Wei ◽  
Tingbo Liu ◽  
...  

Abstract Baicalin is a traditional Chinese medicine with multiple biological effects. Some researches showed baicalin has anti-tumor effects in solid tumor, such as prostate cancer. In order to investigate its effects on proliferation inhibition and apoptosis induction in human lymphoma cell, we treated Burkitt lymphoma cell line CA46 with baicalin in vitro and in vivo of CA46 xenograft. Baicalin remarkably inhibited the cell proliferation, with an IC50 value of 10μM. Apoptosis was remarkably induced by baicalin in a dose-dependent manner, which was detected by Annexin V FITC/PI double staining analysis, TUNEL labeling method and DNA fragmentation respectively. Furthermore, RT-PCR showed that the mRNA expressions of c-myc and bcl-2 in treated CA46 cell decreased in a time-dependent manner. Western-Blot showed that the protein expressions of c-myc, bcl-2, procaspase-3 and PARP(116KD) in baicalin treated CA46 cell were down-regulated, while the expression of PARP(85KD) increased. Based on the results in vitro, we investigated in vivo efficacy of baicalin, alone or in combination with cytotoxic drug VP16, for treatment in CA46 nude mice xenograft. Baicalin with the dosage of 40mg/kg/d and 80kg/mg/d could remarkably inhibit the growth of the tumor compared with control group. Combination of baicalin and VP16 had better anti-tumor effects. Histological examination of tumor samples showed more necrotic cells in treated groups. And obvious apoptosis could be observed by electron microscope. No adverse events were found in treated groups. From above we could conclude that baicalin could efficiently induce proliferation inhibition and apoptosis of CA46 cells in vitro and in vivo, which may be related with the down-regulation of c-myc and bcl-2 expressions, as well as the up-regulation of caspase-3 activity.


2011 ◽  
Vol 39 (06) ◽  
pp. 1193-1206 ◽  
Author(s):  
De-Peng Jiang ◽  
Qi Li ◽  
Jie Yang ◽  
Juliy M. Perelman ◽  
Victor P. Kolosov ◽  
...  

The aim of this study was to investigate the influence of scutellarin on mucus production induced by human neutrophil elastase (HNE) and the possible in vitro and in vivo mechanisms. To this purpose, cells were incubated with saline, scutellarin or gefitinib for 60 min and exposed to 0.1 μM HNE for 24 h. After being pretreated respectively with saline, scutellarin or gefitinib, rats were challenged intratracheally with HNE by means of nebulization for 30 days. The expression of mucin (MUC) 5AC, protein kinase C (PKC), and extracellular signal-regulated kinase 1/2 (ERK1/2) was assessed by ELISA, RT-PCR or Western blotting. The results showed that scutellarin inhibited MUC5AC mRNA and protein expressions induced by HNE in a concentration-dependent manner in vitro. In the in vivo model, scutellarin significantly attenuated MUC5AC mRNA expression and goblet cell hyperplasia in rats treated with HNE for 30 days, as well as decreased the phosporylation of PKC and ERK1/2 compared to the HNE control group. Therefore, our study showed that scutellarin could prevent mucus hypersecretion by inhibiting the PKC-ERK signaling pathway. Inhalation scutellarin may be valuable in the treatment of chronic inflammatory lung disease.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryutaro Furukawa ◽  
Masahiro Kitabatake ◽  
Noriko Ouji-Sageshima ◽  
Yuki Suzuki ◽  
Akiyo Nakano ◽  
...  

AbstractCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread across the world. Inactivating the virus in saliva and the oral cavity represents a reasonable approach to prevent human-to-human transmission because the virus is easily transmitted through oral routes by dispersed saliva. Persimmon-derived tannin is a condensed type of tannin that has strong antioxidant and antimicrobial activity. In this study, we investigated the antiviral effects of persimmon-derived tannin against SARS-CoV-2 in both in vitro and in vivo models. We found that persimmon-derived tannin suppressed SARS-CoV-2 titers measured by plaque assay in vitro in a dose- and time-dependent manner. We then created a Syrian hamster model by inoculating SARS-CoV-2 into hamsters’ mouths. Oral administration of persimmon-derived tannin dissolved in carboxymethyl cellulose before virus inoculation dramatically reduced the severity of pneumonia with lower virus titers compared with a control group inoculated with carboxymethyl cellulose alone. In addition, pre-administration of tannin to uninfected hamsters reduced hamster-to-hamster transmission of SARS-CoV-2 from a cohoused, infected donor cage mate. These data suggest that oral administration of persimmon-derived tannin may help reduce the severity of SARS-CoV-2 infection and transmission of the virus.


2007 ◽  
Vol 2 (1) ◽  
pp. 22
Author(s):  
Enok Sobariah ◽  
Ali Khomsan ◽  
Ingrid S. Surono

<p class="MsoNormal" style="margin: 0cm 12.45pt 6pt 17.85pt; text-align: justify;"><span style="font-size: 10pt;" lang="en-us" xml:lang="en-us">The aim of this study were  to identify the in-vitro tolerance of pro-biotic bacteria to acid and bile salt condition; and  to prove a hypothesis that the supplementation of oxygenated water has a positive effect on the body weight of rat and on viability of pro-biotic bacteria.  The first study was carried out at PAU Laboratory of Bogor Agricultural University, while the second study was conducted at Department of Community Nutrition of Bogor Agricultural University and Microbiology Laboratory of Indonesia Institute of Technology. Forty five rats aged 6 weeks were divided into three groups, i.e., control group without probiotic (a0), Lactobacillus casei Shirota (a1), and Lactobacillus IS-7257 (a2).  Each group (consisting of 5 rats each) has three different treatments, namely, control without oxygenated water (b0), 50 ppm oxygenated water (b2), and 80 ppm oxygenated water (b2). Oxygenated water was administered to the rats twice a day in the morning (3.25 ml) and afternoon (3.00 ml). Observation was carried out on the body  weight of the rats, fecal lactic acid bacteria, coliform, and anaerob bacteria by plate counting, for 4 periods, i.e, prior to the treatment (C0), after three-day treatment (C1), after seven-day treatment (C2), and on the 10<sup>th</sup> day treatment or three days after washed out period. The results indicated that probiotic bacteria are resistant to acid and bile acid condition. Oxygen concentration in water has a significant positive influence on the body weight of rats towards viability of probiotic bacteria (p-level &lt; 0.05).  The supplementation of  oxygenated water 50 ppm significantly increase the population of viable fecal lactic acid bacteria in L. casei Shirota and Lactobacillus IS-7257 groups after 3 and 7 days of treatment.  Lactobacillus IS-7257 gave better response than L. casei Shirota. The supplementation of oxygenated water 80 ppm significantly reduces the fecal coliform in-vivo in both L. casei Shirota and Lactobacillus IS-7257 groups (p-level &lt; 0.05).</span></p>


2018 ◽  
Vol 39 (3) ◽  
pp. 269-284
Author(s):  
G.D. Chechet ◽  
J Yahaya ◽  
A.J. Nok

Animal African trypanosomiasis (AAT) also known as Nagana is a resurgent disease in Africa. Medicinal plants are being used in less developed countries for the treatment of various diseases including trypanosomiasis, due to the high cost of currently available drugs. Most of these plants have been useful sources of treatment of various diseases based on information obtained from folk medicine but have not been scientifically certified. Here, we investigated the in vitro and in vivo anti-trypanosomal potentials of the methanol extract of Aformorsia laxiflora and Khaya senegalensis against T. b. brucei. Phytochemical screening as well as LD50 of the plant extracts was carried out following standard procedures. Parasitemia was monitored daily while Packed Cell Volume was determined at three time points (days 1, 4 and 7) during the course of the infection. The phytochemical analysis showed the presence of saponins, alkaloids, flavonoids, antraquinones, resins and tanins. However, steriods/terpenoids were absent in K. senegalensis but present in A. laxiflora. The toxicity of methanol extract of both A. laxiflora and K. senegalensis was above 5000mg/kg body weight. Methanol extracts of A. laxiflora (leaves) and K. senegalensis (stem bark) showed promising trypanocidal potential in vitro against T. b. brucei at concentrations of 10, 15, 25mg/ml and 40 and 20mg/ml respectively. At these concentrations, both extracts immobilized the parasites within 55mins post-incubation. In general, A. laxiflora leaf extract demonstrated prophylactic activity against T. b. brucei in vivo at a dose of 500mg/Kg body weight particularly in group C animals where a delayed pre-patent period (6 days post-infection), extended survival (14 days post-infection) and significant (P<0.05) reduction in the parasite burden confirmed by an absence of anemia (PCV 47.00±0.8 %) was observed when compared to the infected untreated control group. K. senegalensis extract on the other hand did not show anti-trypanosomal activity in the treated groups (1, 2, and 3). Based on these observations, it was therefore deduced that the methanol extract of leaves of A. laxiflora possessed the ability to ameliorate the burden of the disease and could be a plausible candidate for drug development against the disease.Keywords: Trypanosoma brucei brucei, Afromosia laxiflora, Khaya senegalensis, anti-trypanosomal, in vitro, in vivo


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