69 research outputs found
Perspective: Adhesion Mediated Signal Transduction in Bacterial Pathogens
No full textDuring the infection process, pathogenic bacteria undergo large-scale transcriptional changes to promote virulence and increase intrahost survival. While much of this reprogramming occurs in response to changes in chemical environment, such as nutrient availability and pH, there is increasing evidence that adhesion to host-tissue can also trigger signal transduction pathways resulting in differential gene expression. Determining the molecular mechanisms of adhesion-mediated signaling requires disentangling the contributions of chemical and mechanical stimuli. Here we highlight recent work demonstrating that surface attachment drives a transcriptional response in bacterial pathogens, including uropathogenic Escherichia coli (E. coli), and discuss the complexity of experimental design when dissecting the specific role of adhesion-mediated signaling during infection.Peer reviewe
Involvement Of Mitochondria In Diclofenac – And Ibuprofen- Induced Hepatotoxicity
No full textDiclofenac and ibuprofen are commonly used non-steroidal anti-inflammatory drugs
(NSAIDs) in the treatment of rheumatic diseases. However, these drugs are known
to cause hepatotoxicity in patients. Recent in vitro studies indicated that the
hepatotoxic effects of these NSAIDs are related to their ability to induce apoptosis
by targeting the mitochondria. This study was carried out to investigate and to
compare possible liver perturbation following diclofenac and ibuprofen
administration to rats. Male Sprague-Dawley rats (n=144) were treated with 3mg/kg,
5mg/kg and 1Omg/kg diclofenac and ibuprofen in normal saline, intraperitonealJy at
500~I/rat/day for 15 days. The control group was administered with saline in a
similar manner. Four rats from each group were euthanised every 3 consecutive
days. While 200mg/kg diclofenac and ibuprofen-treated rats (n=4) were euthanised
following a single dose 10 hours post-treatment. Upon euthanisation, the livers were
removed and cleaned with normal saline. A section across the right lobe was taken
and fixed in 10% (v/v %) formal saline and 4% (v/v) glutaraldehyde for light (H&E staining and TUNEL assay) and transmission electron microscopy, respectively. The
remaining samples were kept under -80°C for Western blotting analysis. The three
mg/kg diclofenac administered group at day 15 showed significant presence of
microvesicles and lymphocytic infiltration. The five mg/kg diclofenac-treated rats
revealed significant presence of microvesicles, lymphocytic and neutrophilic
infiltrations at day 15. Liver sections obtained from rats administered with 10 mg/kg
diclofenac showed significant presence of microvesic1es, mild lymphocytic and
neutrophilic infiltration and inflammation. The five mg/kg and 10mg/kg ibuprofeninjected
rats showed significant presence of microvesicles and mild focal
lymphocytic and neutrophilic infiltrations. These observations were mainly seen
around central veins (CVs). In TUNEL assay, 5mg/kg and IOmg/kg diclofenac and
IOmg/kg ibuprofen administered rats, showed apoptotic cells around the CVs at day
15. Ultrastructural study revealed swollen and ruptured mitochondrial membranes in
rats treated with 5mg/kg diclofenac, 10mg/kg diclofenac and 10mg/kg ibuprofen on
day 15. Western blotting analysis showed constant expression of cytochrome c in
liver homogenate and mitochondrial fraction on day 3,6,9, 12 and 15. However no
cytochrome c expression was detected in the cytosolic fraction. In 200 mg/kg
diclofenac and ibuprofen-treated rats, cytochrome c was detected in all 3 fractions;
homogenate, mitochondrial and cytosol. The expression of cytochrome c is higher
density in the cytosol from rats administered with diclofenac when compared to the
expression in cytosol from rats treated with ibuprofen. It can be concluded that
diclofenac is probably more potent in inducing changes in mitochondrial membrane
leading to apoptosis. However, at therapeutic dosage both drugs did not induce
prominent alteration in the mitochondria and the hepatocytes in general
The Prebiotic Role of Polyphenols and the Modulation of Gut Microbiota and Metabolic Parameters by Geraniin and its Enriched Extract in Animal Model
No full textGeraniin is a natural compound present abundantly in the rambutan rind and has the potential to ameliorate diet-induced metabolic syndrome. This study was carried out to identify whether geraniin's interaction with gut microbiota is the main mechanism for its efficacy against metabolic syndrome. Male Sprague Dawley rats were treated with various doses of geraniin and an enriched extract of geraniin (GEE). We observed that 5mg geraniin and 115mg GEE supplementation significantly improved diet-induced metabolic aberrations while increasing the relative abundance of a few butyrate-producing bacteria and plasma butyrate. These findings suggest that geraniin and its enriched extract are promising therapeutic agents against diet-induced metabolic syndrome
Polyphenols as prebiotics in the management of high-fat diet-induced obesity:A systematic review of animal studies
No full textObesity is a disease growing at an alarming rate and numerous preclinical studies have proven the role of polyphenols in managing this disease. This systematic review explores the prebiotic effect of polyphenols in the management of obesity among animals fed on a high-fat diet. A literature search was carried out in PubMed, Scopus, CINAHL, Web of Science, and Embase databases following the PRISMA guidelines. Forty-four studies reported a significant reduction in obesity-related parameters. Most notably, 83% of the studies showed a decrease in either body weight/visceral adiposity/plasma triacylglyceride. Furthermore, 42 studies reported a significant improvement in gut microbiota (GM), significantly affecting the genera Akkermansia, Bacteroides, Blautia, Roseburia, Bifidobacteria, Lactobacillus, Alistipes, and Desulfovibrio. Polyphenols’ anti-obesity, anti-hyperglycaemic, and anti-inflammatory properties were associated with their ability to modulate GM. This review supports the notion of polyphenols as effective prebiotics in ameliorating HFD-induced metabolic derangements in animal models.</p
Morphological alteration in mitochondria following diclofenac and ibuprofen administration.
No full textThis study was conducted to identify and to compare the mitochondrial morphological alterations in livers of rats treated with various doses of diclofenac and ibuprofen. Hundred and forty-four male Sprague Dawley rats were dosed with 3, 5 and 10 mg kg-1 diclofenac and ibuprofen in saline via intraperitoneal injection for 15 days. The control group was administered with saline in a similar manner. Four rats were euthanised every 3 days until day 15. While 200 mg kg-1 diclofenac and ibuprofen-treated rats (n = 4) were euthanized 10 h post-treatment. The livers were removed, cleaned and a section across the right lobe was taken and fixed in 4% (v/v) glutaraldehyde for electron microscopy analysis and the remaining samples were kept at -80°C for Western blot analysis. Five milligram per kilogram and 10 mg kg-1 diclofenac-administered rats for 15 days revealed the presence of enlarged mitochondria, irregular and ruptured mitochondrial membranes. While rats administered with 10 mg kg-1 ibuprofen also showed the presence of mitochondria with irregular membrane structure and ruptured membranes. Western blotting analysis of mitochondrial fractions revealed the expression of cytochrome c in all samples and complete absence of cytochrome c expression in the cytosolic fraction of all samples after day 15. Analysis in 200 mg kg -1 diclofenac and ibuprofen-treated groups, revealed expression of cytochrome c in both mitochondrial and cytosolic fractions. This observation indicates that both diclofenac and ibuprofen may alter the morphology of mitochondria, leading to cytochrome c release into the cytosol. Further studies needs to be conducted to investigate on the activity of the mitochondria following both treatments
The histomorphological analysis of liver following administration of low doses of diclofenac and ibuprofen
No full textThis study was conducted to investigate and to compare liver perturbation following administration of low doses of diclofenac and ibuprofen to rats. Hundred and forty-four male Sprague Dawley rats were dosed with 3, 5 and 10 mg kg-1 diclofenac and ibuprofen in saline via intraperitoneal injection for 15 days. The control group was administered with saline in a similar manner. Four rats were euthanised every three days until day 15. Livers were removed, cleaned and a section across the right lobe was taken and fixed in 10% formalin for light microscopy and TUNEL assay. One-way ANOVA was used to analyse the data. p<0.05 was accepted as significant in this study. Three, 5 and 10 mg kg-1 diclofenac-treated groups and 5, 10 mg kg-1 ibuprofen administered groups showed significant changes compared to saline-treated group at day 15. The changes include presence of focal infiltration by neutrophils and lymphocytes and mild focal necrosis. In 5 and 10 mg kg-1 diclofenac administered groups and 10 mg kg-1 ibuprofen-treated group, apoptotic cells were seen around the perivenular regions (PV) only at day 15. However, not all the PVs were present with apoptotic cells. This study has shown that, diclofenac is probably more potent in inducing histomorphological changes at low doses. Both the drugs seem to exert time and dose dependent liver morphological alterations to the treated animals
The Prebiotic Potential of Geraniin and Geraniin-Enriched Extract against High-Fat-Diet-Induced Metabolic Syndrome in Sprague Dawley Rats
No full textGeraniin, an ellagitannin, has ameliorative properties against high-fat diet (HFD)-induced metabolic syndrome. Since geraniin has poor bioavailability, we hypothesised the interaction of this compound with gut microbiota as the main mechanism for improving metabolic aberrations. Male Sprague Dawley rats were divided into normal diet (ND)- and HFD-fed animals and treated with geraniin and an enriched extract of geraniin (GEE). We observed that 5 mg geraniin and 115 mg GEE supplementation significantly attenuated glucose intolerance, lipopolysaccharide-binding protein, total cholesterol, triacylglyceride, and low-density lipoprotein; improved insulin sensitivity; and significantly increased adiponectin and hepatic PPARα expression. Although geraniin and GEE did not significantly alter the gut microbial composition, we found an increment in the relative abundance of a few butyrate producers such as Alloprevotella, Blautia, Lachnospiraceae NK4A136 group, and Clostridium sensu stricto 1. Geraniin and its enriched extract’s ability to ameliorate metabolic syndrome parameters while positively affecting the growth of butyrate-producing bacteria suggests its potential prebiotic role
Acute oral toxicity of the ellagitannin geraniin and a geraniin-enriched extract from Nephelium lappaceum L rind in Sprague Dawley rats
No full textDespite the lack of its toxicity evaluation, traditional herbal products are being widely used for various health indications. Geraniin, an ellagitannin, is a bioactive compound found in many traditional herbal medicines. In spite its numerous health benefits ranging from anti-inflammatory, anti-hyperglycaemic, hepatoprotective, anti-cancer and anti-microbial, no toxicity data on geraniin is available. The objective of this study is to evaluate the acute oral toxicity of geraniin and an enriched geraniin-extract of Nephelium lappaceum L rind. This study followed the guidelines of the OECD 423 acute oral toxicity test. Subsequent to a single oral administration of the test compounds, the rats were observed for 14 days for signs of toxicity and mortality. Following euthanasia, full blood count, biochemistry of blood and histopathology assessment of organs were carried out. All parameters analysed indicated insignificant difference compared to control. The LD50 cut-off values for both geraniin and geraniin-enriched extract was established to be 2000 mg/kg b. w., following a single oral dose. It was however observed that the hepatocytes of three geraniin-administered rats exhibited a ‘foamy appearance’. As such, the no-observed-adverse-effect level of geraniin is below 2000 mg/kg, while that of geraniin-enriched extract is up to 2000 mg/kg. Further detailed toxicity studies are required to establish geraniin or its enriched extract from Nephelium lappaceum L rind safe for human consumption.</p
Prebiotic potential of polyphenols, its effect on gut microbiota and anthropometric/clinical markers : a systematic review of randomised controlled trials
No full textBackground: Polyphenols have been implicated to have numerous health benefits, and much of these are attributed to the metabolism of phenolic compounds by gut microbiota. The aim of this systematic review was to examine the effects of polyphenol consumption in modulating gut microbiota and anthropometric variables/clinical markers in randomised controlled trials (RCTs). Scope and approach: We systematically searched PubMed, Scopus, Embase, Cochrane library and Web of Science databases from inception to31 st July 2019 following the PRIMSA guidelines.RCTs reporting on the effects of polyphenol consumption on gut microbes, and anthropometric variables (body weight, BMI, waist circumference, hip circumference)/clinical markers (CVD markers, and colon cancer markers) were included in this review. The methodological quality of the studies was assessed using the Cochrane Collaboration's risk of bias tool and Jadad scale. Key findings and conclusion: Seventeen RCTs met the inclusion criteria. Ten studies highlighted significant changes in the microbial profile, while 15 reported significant changes in CVD and colon cancer markers. The univariate correlation data showed a significant correlation between certain genera with clinical markers, specifically TNFα, cholesterol, HDL, CRP, and LPS. In the multivariate analysis, negative correlations were reported between Lactobacillus and TAG, CRP, Bacteroides with TAG, HDL, DBP, and SBP, and Bifidobacterium with cholesterol and CRP. This review supports the notion of polyphenols as prebiotics as significant modulation of intestinal microbes affecting mainly CVD markers were found in most of the RCTs. Further well-structured trials with larger sample size, longer duration, and high-throughput molecular techniques, will provide more conclusive results. Protocol registration number: PROSPERO; CRD42017077577
Geraniin Protects High-Fat Diet-Induced Oxidative Stress in Sprague Dawley Rats
No full textGeraniin, a hydrolysable polyphenol derived from Nephelium lappaceum L. fruit rind, has been shown to possess significant antioxidant activity in vitro and recently been recognized for its therapeutic potential in metabolic syndrome. This study investigated its antioxidative strength and protective effects on organs in high-fat diet (HFD)-induced rodents. Rats were fed HFD for 6 weeks to induce obesity, followed by 10 and 50 mg/kg of geraniin supplementation for 4 weeks to assess its protective potential. The control groups were maintained on standard rat chows and HFD for the same period. At the 10th week, oxidative status was assessed and the pancreas, liver, heart and aorta, kidney, and brain of the Sprague Dawley rats were harvested and subjected to pathological studies. HFD rats demonstrated changes in redox balance; increased protein carbonyl content, decreased levels of superoxide dismutase, glutathione peroxidase, and glutathione reductase with a reduction in the non-enzymatic antioxidant mechanisms and total antioxidant capacity, indicating a higher oxidative stress (OS) index. In addition, HFD rats demonstrated significant diet-induced changes particularly in the pancreas. Four-week oral geraniin supplementation, restored the OS observed in the HFD rats. It was able to restore OS biomarkers, serum antioxidants, and the glutathione redox balance (reduced glutathione/oxidized glutathione ratio) to levels comparable with that of the control group, particularly at dosage of 50 mg geraniin. Geraniin was not toxic to the HFD rats but exhibited protection against glucotoxicity and lipotoxicity particularly in the pancreas of the obese rodents. It is suggested that geraniin has the pharmaceutical potential to be developed as a supplement to primary drugs in the treatment of obesity and its pathophysiological sequels
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