scholarly journals The Effects of a Meldonium Pre-Treatment on the Course of the Faecal-Induced Sepsis in Rats

2021 ◽  
Vol 22 (18) ◽  
pp. 9698
Author(s):  
Siniša Đurašević ◽  
Aleksandra Ružičić ◽  
Iva Lakić ◽  
Tomislav Tosti ◽  
Saša Đurović ◽  
...  

Sepsis is a life-threatening condition caused by the dysregulated and overwhelming response to infection, accompanied by an exaggerated pro-inflammatory state and lipid metabolism disturbance leading to sequential organ failure. Meldonium is an anti-ischemic and anti-inflammatory agent which negatively interferes with lipid metabolism by shifting energy production from fatty acid oxidation to glycolysis, as a less oxygen-demanding pathway. Thus, we investigated the effects of a four-week meldonium pre-treatment on faecal-induced sepsis in Sprague-Dawley male rats. Surprisingly, under septic conditions, meldonium increased animal mortality rate compared with the meldonium non-treated group. However, analysis of the tissue oxidative status did not provide support for the detrimental effects of meldonium, nor did the analysis of the tissue inflammatory status showing anti-inflammatory, anti-apoptotic, and anti-necrotic effects of meldonium. After performing tissue lipidomic analysis, we concluded that the potential cause of the meldonium harmful effect is to be found in the overall decreased lipid metabolism. The present study underlines the importance of uninterrupted energy production in sepsis, closely drawing attention to the possible harmful effects of lipid-mobilization impairment caused by certain therapeutics. This could lead to the much-needed revision of the existing guidelines in the clinical treatment of sepsis while paving the way for discovering new therapeutic approaches.

Author(s):  
sherine ibrahim ◽  
ahmed fayez ◽  
ahmed maher

IntroductionLiver fibrosis is currently the 11th most common cause of death worldwide. Because of self-renewal, available sources for isolation, and high differentiation properties, multipotent mesenchymal stromal stem cells are suggested to be potential tool for treatment of liver fibrosis. In this study, we examined the anti-fibrotic and anti-inflammatory activity of bone marrow-derived multipotent mesenchymal stromal stem cells (MSCs) on liver fibrosis induced by carbon tetrachloride on rats relative to silymarin as a standard drug.Material and methodsThis study was performed on 40 male Sprague Dawley rats divided into 4 groups of ten rats each: Group 1 served as controls, Group 2 served as CCl4 (diseased) group, Group 3 served as silymarin treated group and Group 4 served as MSCs treated group. Liver fibrosis was assessed by determination of liver markers and fibrogenesis related genes together with the anti-inflammatory markers in the liver tissue. DNA fragmentation was assessed by Comet assay.ResultsMSCs treatment reduced all liver fibrosis markers as well as the oxidative stress and inflammatory markers. Additionally, MSCs reduced the expression of integrins and fibronectin compared with the control group as well as decreasing DNA fragmentation.ConclusionsTreatment by MSCs significantly ameliorates liver fibrosis in rats. This amelioration was a result of acting on both the anti-inflammatory and anti-fibrotic activity of hepatocytes.


2019 ◽  
Vol 8 ◽  
Author(s):  
Nadia Rezaei ◽  
Mohammad Hassan Eftekhari ◽  
Nader Tanideh ◽  
Maral Mokhtari ◽  
Zahra Bagheri

Background: Antioxidant therapy has gained attention for the treatment of ulcerative coli­tis (UC). The excessive generation of reactive oxygen/nitrogen species in the gastrointestinal tract increases oxidative stress, thereby leading to antioxidant defense depletion, lipid perox­idation, inflammation, tissue damage, and ulceration. Spirulina platensis (SP) and honey are excellent sources of potent antioxidants such as polyphenols and other bioactive compounds. We aimed to investigate antioxidant and anti-inflammatory effects of honey and SP in com­parison with sulfasalazine (SSZ) and mesalazine on acetic acid-induced colitis (AA-colitis) in rats. Materials and Methods: Fifty-six Sprague Dawley male rats were allocated to sev­en groups, with each group comprising eight rats. UC was induced, except in normal con­trols (NC). All groups received oral treatments for seven days. The normal saline solution of 2 mL was intrarectally administered to the NC group. The AA-colitis and NC groups received 2 mL acetic acid intrarectally as a single dose and 2 mL normal saline for seven consecutive days orally. The mesalazine group received 100 mg/kg mesalazine, the SSZ group 360 mg/kg SSZ, the honey or H group 1 mL honey diluted with 1 mL distilled water, the SH group 1g/kg SP and 1 mL honey, and the SP group 1g/kg SP. After clinical activity score assessment, the rats were sacrificed. Colonic weight/length ratio, prostaglandin E2 (PGE2), myeloperoxidase (MPO), nitric oxide (NO), malondialdehyde (MDA), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), glutathione peroxidase (GPx), total antioxidant capacity (TAC), reduced glutathione (GSH), and superoxide dismutase (SOD) were measured. Colonic histopathological changes were observed microscopically. Results: Treatment of UC with SP, honey, and combination regimen significantly reduced TNF-α, IL-1β, IL-6, MDA, MPO, NO, and PGE2, and increased TAC, GSH, GPx, and SOD in interventional groups compared to the AA-colitis group (P<0.05). Conclusion: Honey and SP might be beneficial food supple­ments for medical nutrition therapy in UC. [GMJ.2019;8:e1095]


2019 ◽  
Vol 20 (4) ◽  
pp. 842 ◽  
Author(s):  
Satoshi Komasa ◽  
Mariko Nishizaki ◽  
Honghao Zhang ◽  
Seiji Takao ◽  
Derong Yin ◽  
...  

Ingredients and surface modification methods are being continually developed to improve osseointegration of dental implants and reduce healing times. In this study, we demonstrate in vitro that, by applying concentrated alkali treatment to NANOZR with strong bending strength and fracture toughness, a significant improvement in the bone differentiation of rat bone marrow cells can be achieved. We investigated the influence of materials modified with this treatment in vivo, on implanted surrounding tissues using polychrome sequential fluorescent labeling and micro-computer tomography scanning. NANOZR implant screws in the alkali-treated group and the untreated group were evaluated after implantation in the femur of Sprague–Dawley male rats, indicating that the amount of new bone in the alkali-modified NANOZR was higher than that of unmodified NANOZR. Alkali-modified NANOZR implants proved to be useful for the creation of new implant materials.


2020 ◽  
Vol 39 (8) ◽  
pp. 1079-1094 ◽  
Author(s):  
H Rehman ◽  
S Jahan ◽  
I Ullah ◽  
P-O Thörnqvist ◽  
M Jabbar ◽  
...  

The present study investigated the reproductive toxicity of furan in an Extended One-Generation Reproductive Toxicity Study in rats. Sprague Dawley F0 weaning rats (30 per sex per group) were exposed to furan orally at 0, 1, 2.5, 5, and 10 mg kg−1 for 10 weeks (males) and 2 weeks (females) and then mated. Results of F0 indicated that in the furan-treated groups (5 mg kg−1 and 10 mg kg−1), body weight (bw) gain decreased during prebreed and gestational period while increased during lactation periods. F0 animals prebreeding exposure resulted in head tilt and foot splay at 10 mg kg−1. Number of live pups at birth were decreased ( p < 0.001) at 10 mg kg−1. At postnatal day (PND) 70, a significant ( p = 0.03) decrease in testosterone levels of male rats and estrogen levels of female rats ( p = 0.05) was observed in 10 mg kg−1 furan-treated group in F1 generation. Luteinizing hormone, follicle-stimulating hormone, and progesterone levels were also reduced, but their reduction was not statistically significant in all groups. In higher dose furan group (10 mg kg−1), testicular and ovarian weights were reduced in F1 generation at PND 70, with decreased daily sperm production ( p = 0.01) and disturbed estrous cyclicity ( p < 0.01). Some histopathological changes were also observed in testis and ovaries in groups whose parents were previously exposed to 10 mg kg−1 bw of furan group. Based on the above results, it is suggested that exposure to food-based contaminant furan induced remarkable changes in the F0 (parental stage) and F1 (offspring, pubertal, and adult stage) generations of Sprague Dawley rats.


2015 ◽  
Vol 100 (11-12) ◽  
pp. 1364-1374 ◽  
Author(s):  
Soykan Dinc ◽  
Muzaffer Caydere ◽  
Giray Akgul ◽  
Erdinc Yenidogan ◽  
Semra Hucumenoglu ◽  
...  

Inflammatory bowel disease is a serious health problem. Although it has been widely investigated, treatment of inflammatory bowel diseases currently remains a challenging clinical problem. Overproduction of nitric oxide has been demonstrated to cause tissue damage and inflammation. In this study, the effect of methylene blue (MB), a well-known inhibitor of nitric oxide synthesis, was investigated in acetic acid (AA)-induced colitis model in Sprague-Dawley rats. Eighty male rats were randomized into 4 groups (control, control MB, colitis, colitis + MB). AA was applied to groups 3 and 4. MB was added into groups 2 and 4. Three days later, animals were killed and the 8 cm distal colonic segment was resected, and the specimens were examined using macroscopical, histological, and biochemical methods. The results of the macroscopic and microscopic examination showed that in group 4 the mucosal damage and inflammation score was significantly lower than group 3. Increased intestinal permeability in acetic acid-administered group was significantly reversed by MB application. Myeloperoxidase activity and malondialdehyde levels increased significantly, while superoxide dismutase and catalase activities were suppressed after AA-administration. These biochemical parameters were reversed in MB-treated group. Administration of acetic acid resulted in increased levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, total nitrite/nitrate levels, and nitric oxide synthase activity. These biochemical alterations were also significantly reversed by MB application. In conclusion, our results indicate that MB decreases the level of nitric oxide and decreases inflammation in acetic acid-induced colitis.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Sen Zhang ◽  
Hongqi Xin ◽  
Yan Li ◽  
Dongming Zhang ◽  
Jing Shi ◽  
...  

Skimmin is one of the major pharmacologically active molecules present inHydrangea paniculata, a medical herb used in the traditional Chinese medicine as an anti-inflammatory agent. In the current study, we attempted to investigate its renoprotective activity and underlying mechanisms in a rat model of membranous glomerulonephritis induced by cationic bovine serum albumin (c-BSA). Sprague-Dawley (SD) rats were divided into five groups, including normal control, model control, Mycophenolate Mofetil-treated group, and two skimming-treated groups (15 mg/kg and 30 mg/kg). Our research showed that treatment with skimmin significantly reduced the levels of blood urea nitrogen (BUN), urinary albumin excretion (UAE), and serum creatinine (Scr) as compared with model control after experimental induction of membranous glomerulonephritis (P<0.01). Moreover, glomerular hypercellularity, tubulointerstitial injury, and glomerular deposition of IgG were less intense after skimmin treatment. By immunochemistry analysis, we demonstrated that skimmin could significantly inhibit interleukin-1β(IL1β) and IL-6 expression (P<0.05), reduce the loss of nephrin and podocin, and suppress the infiltration of renal interstitium by CD3-positive T cell and CD20-positive B cell. These results suggest that treatment with skimmin can significantly improve renal function and suppress the IgG deposition as well as the development of glomerular lesions in a rat model of membranous glomerulonephritis.


2015 ◽  
Vol 113 (8) ◽  
pp. 1207-1219 ◽  
Author(s):  
Pushpan K. Chithra ◽  
G. Sindhu ◽  
V. Shalini ◽  
Rathnam Parvathy ◽  
Ananthasankaran Jayalekshmy ◽  
...  

The present study was carried out to evaluate the anti-atherogenic effect of Njavara rice bran oil (NjRBO) on atherosclerosis by modulating enzymes and genes involved in lipid metabolism in rats fed a high-cholesterol diet (HCD). Adult male rats (Sprague–Dawley strain, weighing 100–120 g) were divided into three groups of nine animals each. Group I served as the control, group II were fed a HCD and group III were fed a HCD and NjRBO (100 mg/kg body weight). The study duration was 60 d. Serum and tissue lipid profile, atherogenic index, enzymes of lipid metabolism, plasma C-reactive protein levels, serum paraoxonase and arylesterase activities, thiobarbituric acid-reactive substances, gene and protein expression of paraoxonase 1 (PON1), PPARα, ATP-binding cassette transporter A1 (ABCA1), apoB and apoA1 in the liver were quantified. Total cholesterol, TAG, phospholipid, NEFA, LDL-cholesterol concentrations in the serum and liver, lipogenic enzyme activities, hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity and atherogenic index were significantly increased in HCD-fed rats, but they decreased after treatment with NjRBO. HDL-cholesterol level and lecithin cholesterol acyl transferase activity were increased in the NjRBO-treated group, but decreased in the HCD-fed group. The expression levels of ABCA1, apoA1, PON1 and PPARα were found to be significantly increased in NjRBO-treated group compared with the HCD-fed group; however, the expression level of apoB was found to be higher in HCD-fed group and lower in the NjRBO-treated group. These data suggest that NjRBO possesses an anti-atherogenic property by modulating lipid metabolism and up-regulating genes involved in reverse cholesterol transport and antioxidative defence mechanism through the induction of the gene expressionPON1.


Author(s):  
Linda Weni ◽  
Harliansyah Harliansyah ◽  
Widayanti Widayanti

Using of natural sources that have anti-inflammatory activity for the prevention and treatment of degenerative diseases began to be further explored. An investigation on the anti-inflammatory activity of the aqueous extract of guava leaves (Psidium guajava L.) from Sawangan, Depok on white male rats of Sprague-Dawley strain had been carried out on the carrageenan-induced paw edema method. To examine the effect of guava extract on subcutan at different doses of 125, 250 and 500 mg/kg of body weight (BW).  Indometacine at dose of 10 mg/kg BW was used as a positive control. Observations were made during five hours with an interval of one hour. These results demonstrate that the percentage of inflammation or edema (% E) optimal at the 4th hour and then decreased at the 5th hour, while the percentage of optimal inhibition occurred at the 5th hour. Guava extract at 125, 250 and 500 mg/kg BW reduced inhibitory percentage activities by 40.81, 55.45 and 43.61% (p< 0.05) respectively. In conclusion, this study suggests that guava extract has anti-inflammatory properties by decreasing edema level.Keywords: Anti-inflammatory, guava leaves, edema.


Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3406
Author(s):  
María José Rodríguez ◽  
Matías Sabaj ◽  
Gerardo Tolosa ◽  
Francisca Herrera Vielma ◽  
María José Zúñiga ◽  
...  

Liver fibrosis is a complex process characterized by the excessive accumulation of extracellular matrix (ECM) and an alteration in liver architecture, as a result of most types of chronic liver diseases such as cirrhosis, hepatocellular carcinoma (HCC) and liver failure. Maresin-1 (MaR1) is derivative of ω-3 docosahexaenoic acid (DHA), which has been shown to have pro-resolutive and anti-inflammatory effects. We tested the hypothesis that the application of MaR1 could prevent the development of fibrosis in an animal model of chronic hepatic damage. Sprague-Dawley rats were induced with liver fibrosis by injections of diethylnitrosamine (DEN) and treated with or without MaR1 for four weeks. In the MaR1-treated animals, levels of AST and ALT were normalized in comparison with DEN alone, the hepatic architecture was improved, and inflammation and necrotic areas were reduced. Cell proliferation, assessed by the mitotic activity index and the expression of Ki-67, was increased in the MaR1-treated group. MaR1 attenuated liver fibrosis and oxidative stress was induced by DEN. Plasma levels of the pro-inflammatory mediators TNF-α and IL-1β were reduced in MaR1-treated animals, whereas the levels of IL-10, an anti-inflammatory cytokine, increased. Interestingly, MaR1 inhibited the translocation of the p65 subunit of NF-κB, while increasing the activation of Nrf2, a key regulator of the antioxidant response. Finally, MaR1 treatment reduced the levels of the pro-fibrotic mediator TGF-β and its receptor, while normalizing the hepatic levels of IGF-1, a proliferative agent. Taken together, these results suggest that MaR1 improves the parameters of DEN-induced liver fibrosis, activating hepatocyte proliferation and decreasing oxidative stress and inflammation. These results open the possibility of MaR1 as a potential therapeutic agent in fibrosis and other liver pathologies.


2006 ◽  
Vol 22 (5) ◽  
pp. 211-216 ◽  
Author(s):  
Halis Köylü ◽  
Hakan Mollaoglu ◽  
Fehmi Ozguner ◽  
Mustafa Nazýroölu ◽  
Namýk Delibap

Microwaves (MW) from cellular phones may affect biological systems by increasing free radicals, which may enhance lipid peroxidation levels of the brain, thus leading to oxidative damage. Melatonin is synthesized in and secreted by the pineal gland at night and exhibits anti-oxidant properties. Several studies suggest that supplementation with anti-oxidant can influence MW-induced brain damage. The present study was designed to determine the effects of MW on the brain lipid peroxidation system, and the possible protective effects of melatonin on brain degeneration induced by MW. Twenty-eight Sprague-Dawley male rats were randomly divided into three groups as follows: (1) sham-operated control group (N-8); (2) study 900-MHz MW-exposed group (N-8); and (3) 900-MHz MW-exposed-melatonin (100 mg/kg sc before daily MW exposure treated group) (N-10). Cortex brain and hippocampus tissues were removed to study the levels of lipid peroxidation as malonyl dialdehyde. The levels of lipid peroxidation in the brain cortex and hippocampus increased in the MW group compared with the control group, although the levels in the hippocampus were decreased by MW-melatonin administration. The brain cortex lipid peroxidation levels were unaffected by melatonin treatment. We conclude that melatonin may prevent MW-induced oxidative changes in the hippocampus by strengthening the anti-oxidant defense system, by reducing oxidative stress products.


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