Total Hydroxyproline Research Articles

A STUDY ON STATUS OF URINARY HYDROXYPROLINE IN POST MENOPAUSAL WOMEN

Introduction: WHO and the Stages of Reproductive Aging Workshop have defined menopausal transition as the time of an increase in follicle-stimulating hormone and either increased variability in menstrual cycle length, two skipped menstrual cycles with 60 days or more of amenorrhea, or both. It concludes with the final menstrual period. Post-menopause begins at that time, although it is not recognized until after 12 months of amenorrhea. During menopause, women face various physiological, psychological, and biochemical changes. Laboratory medicine has given a new background to overcome the clinicianÂÂs diagnostic dilemma. Hydroxyproline is mainly found in collagen and accounts for 13% of total amino acid content and derived from proline by post-translational hydroxylation. Hydroxyproline is derived from another amino acid such as proline. Direct urinary assay of hydroxyproline to measure bone resorption have clinical applications as part of screening programs to assess the risk of osteoporotic fractures. Method: A total of seventy patients with regular medical follow-up records, The Patients were pre and post-menopausal women (35 each) recruited for this study. Patient details like body mass index, education, smoking, alcohol intake, dietary habits, and family history were considered before selecting the patients. Analytical Methods: Urinary Hydroxyproline and Urinary creatinine was estimated by Modified Neumann et al and Spectrophotometric JaffeÂÂs reaction respectively. Result: The study population consisted of 70 participants of premenopausal (n=35) and postmenopausal women (n=35), mean age of 38.11 ± 4.3 and 54.40 ± 4.6 respectively. The bone mineralization marker urinary total hydroxyproline was quantified in pre and post-menopausal women, which is 80.3 ± 75mg/L and 136 ± 103mg/L respectively. The urinary creatinine level in pre and post-menopausal women was 53.7 ± 14.2mg/dL and 37.0 ± 27.3 respectively. The hydroxyproline: creatinine ratio (HCR) was 41% to 69% against the normal reference interval in pre and post-menopausal women. Conclusion: The obtained normative data for the premenopausal woman population would be a new reference range in Indian sub-population or otherwise general population normative reference range commonly being used as a reference interval in all kind of pathophysiological disorders. Hence, the derived parameter confirmed that HCR is the most prognostic significant diagnostic marker in pre and post-menopausal patients.

Bone Alkaline Phosphatase and Urine Hydroxyproline Assay in Pre and Postmenopausal Women in the State of Sikkim and its Correlation with Bone Mineral Density.

Introduction:Osteoporosis could be viewed as a metabolic disease. The WHO guidelines for diagnosing osteoporosis reflect structural damage only and not the metabolic imbalance that leads to it. Biochemical markers of bone turnover have been shown to provide valuable information for diagnosing and monitoring metabolic bone disease. The present study analyzed bone-specific alkaline phosphatase (BALP) and urinary hydroxyproline in pre- and postmenopausal women and correlated them with changes in bone mineral density (BMD) in the state of Sikkim. The study also intended to know the ethnicity-based disease burden in Sikkim.Materials and Methods:A hospital-based cross-sectional study was done at a tertiary hospital in Sikkim. Blood and 24-h urine samples from 50 premenopausal and 50 postmenopausal women were analyzed for total alkaline phosphatase (ALP), BALP, and Urine Hydroxyproline. BMD was measured using the quantitative ultrasound technique by Achilles densitometer.Results:There was a statistically significant increase in serum calcium (P = 0.01), ALP (P = 0.01), and urine hydroxyproline (P = 0.03) levels in postmenopausal women as compared to premenopausal women. Although ALP was higher in postmenopausal women, BALP isoform was more elevated in premenopausal women (P = 0.001). BMD was significantly lower in postmenopausal women (P < 0.001). It was also noted that there was a significant difference in BMD between tribal and nontribal populations (P = 0.003). Total ALP and BALP as the bone formation marker and urine hydroxyproline as a bone resorption marker added statistically significant r to BMD prediction (P < 0.05).Conclusion:In this study, BALP combined with Urine Hydroxyproline was helpful as a screening biomarker to predict osteoporosis in postmenopausal women.

Peculiarities of Collagen Turnover in Aging BALB/c Mice.

Examination of collagen turnover in the liver, lungs, and spleen of BALB/c mice revealed the age-related differences in the levels of hydroxyproline and its fractions. The highest level of total hydroxyproline was observed in the lungs and spleen of young (2-month-old) mice. In the liver, this level attained maximum at the age of 6 months at the expense of elevation of protein-bound hydroxyproline relatively its level in 2-month-old mice. At the age of 12 months, the levels of total hydroxyproline in the liver and spleen were lower than in 6-month-old mice. The decrease in the collagen turnover rate in the liver of 12-month-old mice reflected lower levels of hydroxyproline fractions in comparison with the corresponding values in 6-month-old mice. The rates of collagen turnover in organs differed in mice of different ages: it was maximum in the lungs and spleen of young animals and in the liver of middle-aged mice.

Efficient differentiation of vascular smooth muscle cells from Wharton's Jelly mesenchymal stromal cells using human platelet lysate: A potential cell source for small blood vessel engineering.

The development of fully functional small diameter vascular grafts requires both a properly defined vessel conduit and tissue-specific cellular populations. Mesenchymal stromal cells (MSCs) derived from the Wharton's Jelly (WJ) tissue can be used as a source for obtaining vascular smooth muscle cells (VSMCs), while the human umbilical arteries (hUAs) can serve as a scaffold for blood vessel engineering. To develop VSMCs from WJ-MSCs utilizing umbilical cord blood platelet lysate. WJ-MSCs were isolated and expanded until passage (P) 4. WJ-MSCs were properly defined according to the criteria of the International Society for Cell and Gene Therapy. Then, these cells were differentiated into VSMCs with the use of platelet lysate from umbilical cord blood in combination with ascorbic acid, followed by evaluation at the gene and protein levels. Specifically, gene expression profile analysis of VSMCs for ACTA2, MYH11, TGLN, MYOCD, SOX9, NANOG homeobox, OCT4 and GAPDH, was performed. In addition, immunofluorescence against ACTA2 and MYH11 in combination with DAPI staining was also performed in VSMCs. HUAs were decellularized and served as scaffolds for possible repopulation by VSMCs. Histological and biochemical analyses were performed in repopulated hUAs. WJ-MSCs exhibited fibroblastic morphology, successfully differentiating into "osteocytes", "adipocytes" and "chondrocytes", and were characterized by positive expression (> 90%) of CD90, CD73 and CD105. In addition, WJ-MSCs were successfully differentiated into VSMCs with the proposed differentiation protocol. VSMCs successfully expressed ACTA2, MYH11, MYOCD, TGLN and SOX9. Immunofluorescence results indicated the expression of ACTA2 and MYH11 in VSMCs. In order to determine the functionality of VSMCs, hUAs were isolated and decellularized. Based on histological analysis, decellularized hUAs were free of any cellular or nuclear materials, while their extracellular matrix retained intact. Then, repopulation of decellularized hUAs with VSMCs was performed for 3 wk. Decellularized hUAs were repopulated efficiently by the VSMCs. Biochemical analysis revealed the increase of total hydroyproline and sGAG contents in repopulated hUAs with VSMCs. Specifically, total hydroxyproline and sGAG content after the 1st, 2nd and 3rd wk was 71 ± 10, 74 ± 9 and 86 ± 8 μg hydroxyproline/mg of dry tissue weight and 2 ± 1, 3 ± 1 and 3 ± 1 μg sGAG/mg of dry tissue weight, respectively. Statistically significant differences were observed between all study groups (P < 0.05). VSMCs were successfully obtained from WJ-MSCs with the proposed differentiation protocol. Furthermore, hUAs were efficiently repopulated by VSMCs. Differentiated VSMCs from WJ-MSCs could provide an alternative source of cells for vascular tissue engineering.

Dietary taurine improves muscle growth and texture characteristics in juvenile turbot (Scophthalmus maximus)

A 70-day feeding trial was conducted to analyze the effects of dietary taurine on the muscle growth and texture characteristics in juvenile turbot (Scophthalmus maximus). For the feeding trial, five experimental diets were formulated. The two control diets were designed as follows: the positive control diet (C+) with 60 % of dietary fish meal, the negative control diet (C-) with 45 % of dietary fish meal. Based on the C-, 0.4 %, 1.2 % and 2.0 % of dietary taurine were supplemented, respectively, to formulate the other three experimental diets (T1, T2 and T3, respectively). Results showed that, in regard to the muscle fiber frequency distribution, diameter class 20 was significantly higher in all the dietary taurine supplemented groups than that in the two control groups. Muscle fibers density was significantly higher in 1.2 % of dietary taurine supplemented group than that in the other all groups. The muscle in the T2 group had the highest adhesiveness, and that in the T3 group had the highest hardness. The group with 1.2 % of dietary taurine supplementation had the significantly highest values of the total hydroxyproline (0.48 mg/g) and the total collagen (3.84 mg/g) among all the groups. In conclusion, 1.2 % of taurine supplementation in low fish meal (45 %) diet showed the significantly higher hyperplasia fiber growth and textural properties in turbot muscle.

Vitrified Human Umbilical Arteries as Potential Grafts for Vascular Tissue Engineering.

The development of a biological based small diameter vascular graft (d < 6mm), that can be properly stored over a long time period at - 196°C, in order to directly be used to the patients, still remains a challenge. In this study the decellularized umbilical arteries (UAs) where vitrified, evaluated their composition and implanted to a porcine model, thus serving as vascular graft. Human UAs were decellularized using 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) and sodium dodecyl sulfate (SDS) detergents. Then, vitrified with vitrification solution 55 (VS55) solution, remained for 6months in liquid nitrogen and their extracellular matrix composition was compared to conventionally cryopreserved UAs. Additionally, total hydroxyproline, sulphated glycosaminoglycan and DNA content were quantified in all samples. Finally, the vitrified umbilical arteries implanted as common carotid artery interposition graft to a porcine animal model. Decellularized and vitrified UAs characterized by proper preservation of extracellular matrix proteins and tissue architecture, whereas conventionally cryopreserved samples exhibited a disorganized structure. Total hydroxyproline content was preserved, although sulphated glycosaminoglycan and DNA contents presented significantly alterations in all samples. Implanted UAs successfully recellularized and remodeled as indicated by the histological analysis. Decellularized and vitrified UAs retained their structure function properties and can be possible used as an alternative source for readily accessible small diameter vascular grafts.

Сравнительный анализ биохимических показателей при ревматических заболеваниях взрослых и детей в норме и патологии

Collagen is an intercellular substance of connective tissue, it plays an important role in the physiological processes of the body. Collagen consists of three polypeptide chains twisted in a spiral and in order to stabilize this structure, hydroxyproline is needed, its hydroxyl groups are involved in the formation of hydrogen bonds between the chains of polypeptides. The peculiarity of collagen is that 14% of the amino acids it contains are hydroxyproline, an amino acid that is not contained in other proteins. In this regard, the content of hydroxyproline in blood serum was used to assess the metabolism of collagen in the body. We determined the content of hydroxyproline fractions in blood serum. Calcium, fibrinogen, erythrocyte settling rate and alkaline phosphatase level in children and adults with joint disease were also determined. The control group included healthy children and adults. The total hydroxyproline content in children with the disease was 9-11% lower than in healthy children. In adults with joint diseases, the total hydroxyproline content was 11% higher than in healthy patients. In children and adults with rheumatic diseases, the peptide-bound hydroxyproline content increased, while the protein-bound hydroxyproline content decreased in comparison with the control group control parameters. No significant changes in the content of calcium and fibrinogen were noted, but the level of alkaline phosphatase and the rate of erythrocyte sedimentation was increased, which is typical for people with inflammatory diseases.

Effect of Ficus carica L. leaves extract loaded gold nanoparticles against cisplatin-induced acute kidney injury

BackgroundCisplatin (CisPt) is one of the most widely used and highly effective drugs for the treatment of various solid tumors, unfortunately acute kidney injury (AKI) is considered one of its side effects through several mechanisms including production of reactive oxygen species (ROS), pro-inflammatory and pro-fibrotic cytokines. Due to the poor effect of AKI therapy, the use of nanoparticles loaded with natural extracts for delivering to the kidney molecules are desirable. AimThis study aims to investigate the effectiveness of different concentrations of gold nanoparticles (Au-NPs) as a carrier for Ficus carica L. (Fig) leaves extract against CisPt induced AKI. MethodsSeventy male albino rats were used and divided into seven groups. After the experimental period, blood was withdrawn, serum was separated for determination of urea, creatinine, homocystein (Hcy) and folic acid while reduced glutathione (GSH), nitric oxide (NO), malondialdehyde (MDA), total antioxidant capacity (TAC) and hydroxyproline content (Hyp) were evaluated in kidney tissue homogenate. ResultsCisPt induced AKI in rats and results in a significant increase in the levels of serum urea, creatinine, Hcy and kidney Hyp, lipid peroxidation along with a significant reduction of kidney GSH, NO and TAC compared to the control rats. Treatment with Au-NPs and Fig extract particularly in a ratio of (3:2) respectively was shown to improve renal functions with efficient capacity in scavenging ROS and reduced AKI severity. ConclusionAu-NPs enhanced the anti-oxidative properties of the Fig extract in targeting kidney damaged tissue and reduced oxidative toxicity induced by CisPt.

MON-476 Growth Hormone and the Glomerular Podocyte: Studies of Podocyte-Specific Growth Hormone Receptor Gene Deletion in Mice

Previous research has suggested a role for growth hormone (GH) in the development of kidney disease. Evidence of increased glomerular size and sclerosis in bovine GH (bGH) overproducing animals suggests that excess GH action may cause or exacerbate glomerular damage. Within the glomerulus, the podocyte plays the role of forming a filtration barrier called the slit diaphragm. This cell is known to be dysfunctional in many models of nephropathy and is also a direct target of GH. To explore the mechanisms by which GH impacts the glomerulus, we have developed a transgenic mouse, the podocyte-specific GH receptor gene-disrupted mouse (podGHR-/-). These mice were generated on a C57BL/6J background using Cre-Lox transgenic methods. To examine the effects of high GH levels on the podocyte, these mice were crossed with bovine GH (bGH) overproducing mice and studied at several time points over the course of a year, alongside wild-type control mice and podGHR-/- mice lacking bGH overexpression. Various metabolic and physiologic assays were performed on these mice, including glomerular filtration rate (GFR) testing, glucose and insulin tolerance testing, body composition analysis, and urine & serum analysis. Histological analyses were also performed. Podocyte-specific GHR gene-deletion was associated with increased GFR in male podGHR-/- mice at 54 weeks of age, and with decreased GFR in male podGHR-/- mice with bGH overexpression at 54 weeks of age. PodGHR-/- male mice exhibited significantly decreased total kidney hydroxyproline content at 54 weeks of age as well as decreased glomerular trichrome stain deposition. Both male and female podGHR-/- mice showed decreased glomerular periodic acid Schiff stain deposition at 54 weeks of age. These results suggest a role for podocyte GH activity in the regulation of GFR in the aging and diseased kidney, as well as a role for GH in directing the deposition of collagen and glycosaminoglycans in glomerulus via the podocyte.

Correlation between the Melatonin Level and Indicators of Aging and Fibrosis in Men in the European Part of the Arctic Zone of the Russian Federation

The results of the correlation analysis between the metabolite melatonin - 6-sulfatoxymelatonin (6-SMT) in the urine and the indicators of aging, interstitial fibrosis, the system of antioxidant protection in men in the Arctic are presented. Negative correlation of medium strength between 6-SMT with calendar age, biological age and molecular marker of aging p16INK4a in leukocytes was noted. A relationship of 6-SMT to fibrosis indices was found. It manifested itself in a negative correlation with sulfated glycosaminoglycans in the urine, with collagen markers: free hydroxyproline, peptide-linked hydroxyproline, and total hydroxyproline. Age-related decrease in the level of 6-SMT may be associated with an age-related increase in interstitial fibrosis in northerners. A positive correlation of medium strength between 6-SMT and hormones: free testosterone level (r=0,53, p=0,0002), total testosterone (r=0,43, p=0,003) and cortisol (r=0,33, p=0,007) was shown. Negative correlations of 6-SMT with the content of ceruloplasmin (r=-0,63, p=0,001) and SCORE scale (r=-0,52, p=0,001) indicate the relationship between melatonin and the antioxidant defense system and the risk of cardiovascular pathology.The results of the correlation analysis between the metabolite melatonin - 6-sulfatoxymelatonin (6-SMT) in the urine and the indicators of aging, interstitial fibrosis, the system of antioxidant protection in men in the Arctic are presented. Negative correlation of medium strength between 6-SMT with calendar age, biological age and molecular marker of aging p16INK4a in leukocytes was noted. A relationship of 6-SMT to fibrosis indices was found. It manifested itself in a negative correlation with sulfated glycosaminoglycans in the urine, with collagen markers: free hydroxyproline, peptide-linked hydroxyproline, and total hydroxyproline. Age-related decrease in the level of 6-SMT may be associated with an age-related increase in interstitial fibrosis in northerners. A positive correlation of medium strength between 6-SMT and hormones: free testosterone level (r=0,53, p=0,0002), total testosterone (r=0,43, p=0,003) and cortisol (r=0,33, p=0,007) was shown. Negative correlations of 6-SMT with the content of ceruloplasmin (r=-0,63, p=0,001) and SCORE scale (r=-0,52, p=0,001) indicate the relationship between melatonin and the antioxidant defense system and the risk of cardiovascular pathology.

Fish Collagen Surgical Compress Repairing Characteristics on Wound Healing Process In Vivo.

The development of biomaterials with the potential to accelerate wound healing is a great challenge in biomedicine. In this study, four types of samples including pepsin soluble collagen sponge (PCS), acid soluble collagen sponge (ACS), bovine collagen electrospun I (BCE I) and bovine collagen electrospun II (BCE II) were used as wound dressing materials. We showed that the PCS, ACS, BCE I and BCE II treated rats increased the percentage of wound contraction, reduced the inflammatory infiltration, and accelerated the epithelization and healing. PCS, ACS, BCE I, and BCE II significantly enhanced the total protein and hydroxyproline level in rats. ACS could induce more fibroblasts proliferation and differentiation than PCS, however, both PCS and ACS had a lower effect than BCE I and BCE II. PCS, ACS, BCE I, and BCE II could regulate deposition of collagen, which led to excellent alignment in the wound healing process. There were similar effects on inducing the level of cytokines including EGF, FGF, and vascular endothelial marker CD31 among these four groups. Accordingly, this study disclosed that collagens (PCS and ACS) from tilapia skin and bovine collagen electrospun (BCE I and BCE II) have significant bioactivity and could accelerate wound healing rapidly and effectively in rat model.

Genistein attenuates renal fibrosis in streptozotocin‑induced diabetic rats

The present study aimed to investigate the antifibrogenic effects of genistein (GEN) on the kidney in streptozotocin (STZ)-induced diabetic rats and to determine the associated mechanisms. Rats were randomized into four groups: Normal control (N), STZ (S), L (STZ + low-dose GEN) and H (STZ + high-dose GEN). After 8 weeks, the fasting blood glucose (FBG) level, the ratio of kidney weight to body weight (renal index), 24-h urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), renal total antioxidant capacity (T-AOC), superoxide dismutase (SOD), lipid peroxidation (LPO), malondialdehyde (MDA) and hydroxyproline (Hyp) contents were measured. The histomorphology and ultrastructure of the kidney were also assessed. In addition, mRNA expression levels of transforming growth factor-β1 (TGF-β1) and protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), TGF-β1, mothers against decapentaplegic homolog 3 (Smad3), phosphorylated (p)-Smad3 and collagen IV were estimated. Compared with group N, the levels of FBG, renal index, 24-h urine protein, BUN, SCr, LPO, MDA and Hyp were increased, whereas the levels of T-AOC and SOD were decreased in group S. The structure of renal tissue was damaged, and the expression of Nrf2, HO-1 and NQO1 were reduced, whereas the expression of TGF-β1, Smad3, p-Smad3 and collagen IV were increased in group S. Compared with group S, the aforementioned indices were improved in groups L and H. In conclusion, GEN exhibited reno-protective effects in diabetic rats and its mechanisms may be associated with the inhibition of oxidative stress by activating the Nrf2-HO-1/NQO1 pathway, and the alleviation of renal fibrosis by suppressing the TGF-β1/Smad3 pathway.

BML-111 suppresses TGF-β1-induced lung fibroblast activation in�vitro and decreases experimental pulmonary fibrosis in�vivo

Pulmonary fibrosis is an aggressive end-stage disease. Transforming growth factor-β1 (TGF-β1) mediates lung fibroblast activation and is essential for the progress of pulmonary fibrosis. BML-111, a lipoxinA4 (LXA4) receptor (ALX) agonist, has been reported to possess anti-fibrotic properties. The present study aimed to elucidate whether BML-111 inhibits TGF-β1-induced mouse embryo lung fibroblast (NIH3T3 cell line) activation in vitro and bleomycin (BLM)-induced pulmonary fibrosis in vivo. In vitro experiments demonstrated that BML-111 treatment inhibits TGF-β1-induced NIH3T3 cell viability and the expression of smooth muscle α actin (α-SMA), fibronectin and total collagen. Furthermore, this suppressive effect was associated with mothers against decapentaplegic homolog (Smad)2/3, extracellular signal-regulated kinase (ERK) and Akt phosphorylation interference. In vivo experiments revealed that BML-111 treatment markedly improved survival rate and ameliorated the destruction of lung tissue structure. It also reduced interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and TGF-β1 expression in the BLM intratracheal mouse model. In addition, the expression ofα-SMA and extracellular matrix (ECM) deposition (total collagen, hydroxyproline and fibronectin) were also suppressed following BML-111 treatment. However, BOC-2, an antagonist of ALX, partially weakened the effects of BML-111. In conclusion, these results indicated that BML-111 inhibits TGF-β1-induced fibroblasts activation and alleviates BLM-induced pulmonary fibrosis. Therefore, BML-111 may be used as a potential therapeutic agent for pulmonary fibrosis treatment.

A small molecule fibrokinase inhibitor in a model of fibropolycystic hepatorenal disease.

AIMTo evaluate the novel platelet-derived growth factor receptor and vascular endothelial growth factor receptor dual kinase inhibitor ANG3070 in a polycystic kidney disease-congenital hepatic fibrosis model.METHODSAt 6 wk of age, PCK rats were randomized to vehicle or ANG3070 for 4 wk. At 10 wk, 24 h urine and left kidneys were collected and rats were continued on treatment for 4 wk. At 14 wk, 24 h urine was collected, rats were sacrificed, and liver and right kidneys were collected for histological evaluation. For Western blot studies, PCK rats were treated with vehicle or ANG3070 for 7 d and sacrificed approximately 30 min after the last treatments.RESULTSCompared to the wild-type cohort, the PCK kidney (Vehicle cohort) exhibited a marked increase in kidney and liver mass, hepato-renal cystic volume, hepato-renal fibrosis and hepato-renal injury biomarkers. Intervention with ANG3070 in PCK rats decreased kidney weight, reduced renal cystic volume and reduced total kidney hydroxyproline, indicating significantly reduced rental interstitial fibrosis compared to the PCK-Vehicle cohort. ANG3070 treatment also mitigated several markers of kidney injury, including urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, cystatin C and interleukin-18 levels. In addition, this treatment attenuated key indices of renal dysfunction, including proteinuria, albuminuria and serum blood urea nitrogen and creatinine, and significantly improved renal function compared to the PCK-Vehicle cohort. ANG3070 treatment also significantly decreased liver enlargement, hepatic lesions, and liver fibrosis, and mitigated liver dysfunction compared to the PCK-Vehicle cohort.CONCLUSIONThese results suggest that ANG3070 has the potential to slow disease, and may serve as a bridge toward hepato-renal transplantation in patients with fibropolycystic disease.

Evaluation of antifibrotic effects of coffee and cocoa extracts in rats with thioacetamide-induced fibrosis

Epidemiological data demonstrate an inverse relationship between consumption of coffee as well as other beverages containing methylxanthines and liver fibrosis. The mechanism may include the action of not only methylxanthines but also phenolic compounds. Regarding coffee and cocoa, the levels of phenolic compounds strongly depend on the form of beans, i.e., raw (green) vs. roasted. The aim of this study was to evaluate the antifibrotic effects of coffee and cocoa extracts (both from green and roasted beans) on liver fibrosis progression in thioacetamide (TAA)-treated rats. Among the investigated extracts, only green coffee extract developed a more pronounced antifibrotic effect, partially preventing TAA-induced liver fibrosis, confirmed by the significant decrease of both total and relative hydroxyproline contents in the liver.

PROTECTIVE EFFECT OF DIOSGENIN AGAINST CARBON TETRACHLORIDE AND CISPLATIN INDUCED HEPATOTOXICITY IN RATS

Background: Activation of hepatic stellate cells (HSC) plays central role in the development of liver fibrosis. In HSC activation, the transforming growth factor-1 (TGF-1) is considered to be the main stimuli factor. Diosgenin are the steroidal saponin and found in Trigonella foenum graecum Linn (Fenugreek) and some other species of Dioscorea. Diosgenin attenuates HSC activation by inhibiting transforming growth factor. Aim: In present study an attempt was made to explore the effect of diosgenin on liver fibrosis. Methods: Liver fibrosis was induced in rats by carbon tetrachloride (CCl4) 1 ml/kg intraperitoneally twice a week for 28 days and cisplatin 3mg/kg intraperitoneally at 0, 1, 3 week for 4 weeks. The extent of liver fibrosis was assessed by measuring the weight of liver and levels of total bilirubin (TBL), hydroxyproline (HP) and serum enzymes due to deposition of extracellular matrix (ECM). Results: The administration of diosgenin reduced the liver weight of CCl4 and cisplatin treated animals and reduced the TBL, HP level and serum enzymes significantly and inhibited liver fibrosis induced by CCl4 and cisplatin. Conclusion: The result obtained in the present investigation, Diosgenin treatment exerted significant hepatoprotective effect in animals by inhibiting ECM deposition and HSCs activation.

Protective Effect of Nigella Sativa in an Animal Model of Colon Anastomosis With Ischemia/Reperfusion Injury

Objective: Anastomotic leaks are one of the chief complications after gastrointestinal surgery. The aim of this study was to evaluate whether Nigella sativa administration protects against ischemia/reperfusion injury on healing of colonic anastomosis in rats. Method: Thirty male Wistar albino rats, weighing between 200 and 240 g, were used in the study. They were randomly divided into three groups (n = 10 for each group): Anastomosis (group 1), anastomosis and ischemia/reperfusion injury (group 2), and treatment group of anastomosis, ischemia/reperfusion injury, and Nigella sativa (group 3). After 7 days, serum, plasma, and colonic tissue were obtained and then all rats were sacrificed. Tissue and serum level of total oxidant status, total antioxidant status, total thiol levels, hydroxyproline, interleukin-6, and TNF-alpha were determined and specimens were histopathologically evaluated. Results: In the Nigella sativa treated rats, serum hydroxyproline levels were significantly higher, while tissue levels were significantly lower than those seen in group 1 and group 2 (P = 0.007, P = 0.01, respectively). In the Nigella sativa group, the serum levels of TNF-α were significantly lower than those seen in group 1 and 2 (P = 0.001). Also, in group 3, the tissue IL-6 level was significantly higher than that seen in group 1 and group 2 (P = 0.009). The histopathologic analysis showed less edema and inflammatory cell infiltration in the Nigella sativa treated group, as well as a statistically significant difference according to the Chiu classification (P &amp;lt; 0.05). Conclusion: The results of this study indicate that Nigella sativa has a protective and therapeutic effect against ischemia/reperfusion injury on the healing of colonic anastomosis in rats.

Pan-PPAR agonist IVA337 is effective in experimental lung fibrosis and pulmonary hypertension

ObjectiveTo evaluate the antifibrotic effects of the pan-peroxisome proliferator-activated receptor (PPAR) agonist IVA337 in preclinical mouse models of pulmonary fibrosis and related pulmonary hypertension (PH).MethodsIVA337 has been evaluated in the...

Assessment of physico-chemical traits related to eating quality of young dairy bull beef at different ageing times using Raman spectroscopy and chemometrics

Raman spectroscopy and chemometrics were investigated for the prediction of eating quality related physico-chemical traits of Holstein-Friesian bull beef. Raman spectra were collected on the 3rd, 7th and 14th days post-mortem. A frequency range of 1300–2800cm−1 was used for partial least squares (PLS) modelling. PLS regression (PLSR) models for the prediction of WBSF and cook loss achieved an R2CV of 0.75 with RMSECV of 6.82 N and an R2CV of 0.77 with RMSECV of 0.97%w/w respectively. For the prediction of intramuscular fat, moisture and crude protein content, R2CV values were 0.85, 0.91 and 0.70 with RMSECV of 0.52%w/w, 0.39%w/w and 0.38%w/w respectively. An R2CV of 0.79 was achieved for the prediction of both total collagen and hydroxyproline content, while for collagen solubility the R2CV was 0.88. All samples (100%) from 15- and 19-month old bulls were correctly classified using PLS discriminant analysis (PLS-DA), while 86.7% of samples from different muscles (longissimus thoracis, semitendinosus and gluteus medius) were correctly classified. In general, PLSR models using Raman spectra on the 3rd day post-mortem had better prediction performance than those on the 7th and 14th days. Raman spectroscopy and chemometrics have potential to assess several beef physical and chemical quality traits.

Chinese medicine CGA formula ameliorates DMN-induced liver fibrosis in rats via inhibiting MMP2/9, TIMP1/2 and the TGF-β/Smad signaling pathways.

Chinese medicine CGA formula consists of polysaccharide from Cordyceps sinensis mycelia (CS-PS), gypenosides and amygdalin, which is derived from Fuzheng Huayu (FZHY) capsule for treating liver fibrosis. In this study we attempted to confirm the therapeutic effects of CGA formula in dimethylnitrosamine (DMN)-induced liver fibrosis in rats, and to identify the mechanisms of anti-fibrotic actions. Rats were injected with DMN (10 mg·kg(-1)·d(-1), ip) for 3 consecutive days per week over a 4-week period. The rats then were orally administered with CGA formula (CS-PS 60 mg·kg(-1)·d(-1), gypenosides 50 mg·kg(-1)·d(-1) and amygdalin 80 mg·kg(-1)·d(-1)) daily in the next 2 weeks. CS-PS, gypenosides or amygdalin alone were administered as individual component controls, whereas colchicine and FZHY were used as positive controls. Serum biomarkers were measured. Hepatic injury, collagen deposition and stellate cell activation were examined. The MMP activities, expression of TIMP protein and proteins involved in the TGF-β1/Smad signaling pathways in liver tissues were assayed. In DMN-treated rats, administration of CGA formula significantly decreased serum ALT, AST and total bilirubin and hepatic hydroxyproline levels, increased serum albumin level, and attenuated liver fibrosis as shown by histological examination. Furthermore, these effects were comparable to those caused by administration of FZHY, and superior to those caused by administration of colchicine or the individual components of CGA formula. Moreover, administration of CGA formula significantly decreased the protein levels of α-SMA, TGF-β1, TGF-β1 receptor (TβR-I), p-TβR-I, p-TβR-II, p-Smad2, p-Smad3, TIMP1 and TIMP2, as well as MMP2 and MMP9 activities in liver tissues of DMN-treated rats. Chinese medicine CGA formula ameliorates DMN-induced liver fibrosis in rats, and this effect was likely associated with the down-regulation of MMP2/9 activities, TIMP1/2 protein expression and the TGF-β1/Smad signaling pathways in the liver.