Enhanced Collagen Content Research Articles

Zymosan A Improved Doxorubicin-Induced Ventricular Remodeling by Evoking Heightened Cardiac Inflammatory Responses and Healing in Mice.

Background Doxorubicin-induced myocardial injury is reflected by the presence of vacuolization in both clinical and animal models. The lack of scar tissue to replace the vacuolizated cardiomyocytes indicates that insufficient cardiac inflammation and healing occurred following doxorubicin injection. Whether improved macrophage activity by zymosan A (zymosan) ameliorates doxorubicin-induced ventricular remodeling in mice is unknown. Methods and Results Mice were intravenously injected with vehicle or doxorubicin (5 mg/kg per week, 4 weeks), and cardiac structure and function were assessed by echocardiography. Two distinct macrophage subsets in hearts following doxorubicin injection were measured at different time points by flow cytometry. Moreover, cardiomyocyte vacuolization, capillary density, collagen content, and ventricular tensile strength were assessed. The therapeutic effect of zymosan (3 mg/kg, single injection) on doxorubicin-induced changes in the aforementioned parameters was determined. At the cellular level, the polarization of monocytes to proinflammatory or reparative macrophages were measured, with or without doxorubicin (0.25 and 0.5 μmol/L). Doxorubicin led to less proinflammatory and reparative macrophage infiltration in the heart in the early phase, with decreased cardiac capillary density and collagen III in the chronic phase. In cell culture, doxorubicin (0.5 μmol/L) repressed macrophage transition toward both proinflammatory and reparative subset. Zymosan enhanced both proinflammatory and reparative macrophage infiltration in doxorubicin-injected hearts, evoking a heightened acute inflammatory response. Zymosan alleviated doxorubicin-induced cardiomyocyte vacuolization in the chronic phase, in parallel with enhanced collagen content, capillary density, and ventricular tensile strength. Conclusions Zymosan improved cardiac healing and ameliorated doxorubicin-induced ventricular remodeling and dysfunction by activating macrophages at an optimal time.

Enhancements in flavor substances, mouthfeel characteristics and collagen synthesis in the muscle of sub-adult grass carp (Ctenopharyngodon Idella): Application of a dietary lysine nutrition strategy

The growth performance, flavor substances, mouthfeel characteristics and collagen synthesis in the muscle of sub-adult grass carp (659.07 ± 0.74 g) were investigated after 60-day feeding with graded dietary levels of lysine (6.0–17.0 g/kg diet). The results showed that optimal dietary lysine levels boosted the growth of grass carp. Proper dietary lysine levels improved muscle inosine monophosphate, free amino acids, unsaturated fatty acid content, water holding capacity, pH and shear force (hardness). The diets also decreased lactate content, and enhanced collagen content by increasing transcription, translation and post-translational modifications of type I collagen, probably via activating TGF-β1/Smads and PI3K/Akt/p70S6k/la ribonucleoprotein domain family member 6 (LARP6) signaling; this enhanced prolyl 4-hydroxylase (P4H) and lysyl hydroxylase (LOX) content, thereby improving the flavor and mouthfeel of muscle. In summary, this research indicated that dietary lysine could lead to the enhancement of muscle flavor substances, mouthfeel characteristics and type I collagen synthesis in sub-adult grass carp. Based on the PWG and shear force, the dietary requirements of lysine for sub-adult grass carp are 13.43 and 12.96 g/kg, respectively.

Gestational and Breastfeeding Low-Protein Intake on Blood Pressure, Kidney Structure, and Renal Function in Male Rat Offspring in Adulthood.

Background: Our previous studies demonstrated that maternal protein-restricted (low-protein, LP) 16-week-old offspring had pronounced nephron number reduction and arterial hypertension associated with an unchanged glomerular filtration rate (GFR). An enhanced gomerular area may be related to increased glomerular filtration and overflow, which accounts for glomerular filtration barrier breakdown and early glomerulosclerosis. The effect of protein restriction during gestational and breastfeeding periods is unknown. Method: The functional e-structural kidney evaluation was obtained using lithium and creatinine clearance, kidney morphometry, immunoblotting, and immunostaining analysis in 16 and 24-week-old LP offspring compared to age-matched NP progeny. Results: Low protein rats’ progeny had significantly reduced birth weight, without previous catch-up growth phenomena, in parallel with a decreased adiposity index. Transforming growth factor-beta 1 (TGF-β1) glomerular expression was significantly enhanced in the LP group. Also, the LP offspring had a 38% lower nephron number and an increased glomerular volume. They also presented with a higher cardiac index and arterial blood pressure compared with age-matched NP offspring. The LP rats exhibited augmented Na+/K+-ATPase in the proximal segments, and NOS1 immunoreactivity in whole renal tissue was associated with sodium retention in the proximal nephron segments. We also found significantly enhanced collagen content associated with increased TGFβ1 and ZEB1/2 renal immunoreactivity in LP offspring compared with NP offspring. Increased hypertrophy markers in LP podocytes were associated with an amplified IL-6/STAT3 pathway activity. Conclusion: To our knowledge, these are the first data demonstrating renal functional and structural changes in protein restriction during gestation and lactation model of fetal programming. The fetal-programmed adult offspring showed pronounced structural glomerular disorders with an accentuated and advanced fibrosis stage, without a change in the GFR. These findings suggest that the glomerular enhanced TGF-β1 action may induce ZEB1/2 expression that may cause glomeruli epithelial-to-mesenchymal transition. Besides, decreased nephron number in the LP offspring with preserved glomerular function may be related to protective or even attenuate the activated IL-6/STAT3 pathway.

Enhanced tendon restoration effects of anti-inflammatory, lactoferrin-immobilized, heparin-polymeric nanoparticles in an Achilles tendinitis rat model

Gradual wear and tear can cause a local inflammatory response in tendons. The trauma and inflammatory reaction eventually impair the biomechanical properties of the tendon. In this study, we prepared lactoferrin-immobilized, heparin-anchored, poly(lactic-co-glycolic acid) nanoparticles (LF/Hep-PLGA NPs) and evaluated their in vitro anti-inflammatory effects on interleukin-1β (IL-1β)-treated tenocytes and in vivo tendon healing effects in a rat model of Achilles tendinitis. Long-term LF-deliverable NPs (LF/Hep-PLGA NPs) remarkably decreased mRNA levels of pro-inflammatory factors [cyclooxygenase-2 (COX-2), IL-1β, matrix metalloproteinase-3 (MMP-3), MMP-13, IL-6, and tumor necrosis factor-α (TNF-α)] and increased mRNA levels of anti-inflammatory cytokines (IL-4 and IL-10) in both IL-1β-treated tenocytes and the Achilles tendons of a collagenase-induced Achilles tendinitis rat model. Interestingly, anti-inflammatory LF/Hep-PLGA NPs greatly enhanced collagen content, mRNA levels of tenogenic markers [collagen type I (COL1A1), decorin (DCN), tenascin-C (TNC)], and biomechanical properties such as tendon stiffness and tensile strength. These results suggest that anti-inflammatory LF/Hep-PLGA NPs are effective at restoring tendons in Achilles tendinitis.

Islets of Langerhans phenotype alterations induced by fatty diet and physical activity levels in Wistar rats.

Physical inactivity (PIn) and a fatty diet (FD) are closely linked to development of metabolic syndrome (MetS), overloading the endocrine pancreas seeking energy homeostasis. However, the relative contribution of FD and PIn to the pancreatic overload is unknown. The aim of this study was to verify the isolated and conjugated influence of FD and PIn in the islets of Langer hans (islets) structure and function related to overload in Wistar rats. Male Wistar rats were divided into four groups (n = 10/group): active groups, fed with fat (AFD) or standard (ASD) diet; and physically inactive groups, fed with fat (SFD) or standard (SSD) diet for 21 wk. Glucose tolerance (GT) and insulin sensitivity (IS) were assessed before sacrifice. Retroperitoneal adipose tissue and pancreas were weighted (PW), and pancreas samples processed for histologic analyses. Only the FD-fed animals presented MS. Compared with standard diet, FD impaired GT and IS, decreased PW, and enlarged islets dimensions, with islets cellular death, inflammatory response, and enhanced collagen content, which were attenuated in AFD. Independent of the diet, PIn groups presented higher amounts of islets connective tissue, but without influence on inflammatory reaction and cellular death. The GT impairment was higher in the FD-fed groups, whereas the decreased IS was more pronounced in the PIn groups. FD induced MS with detrimental effects on pancreas overload, inducing islets morphologic and functional maladaptation, which were attenuated in active animals. Physical activity was not able to prevent FD-induced MS. FD showed a negative influence on GT, whereas PIn mainly affected IS.

Intravenous Statin Administration During Myocardial Infarction Compared With Oral Post-Infarct Administration

BackgroundBeyond lipid-lowering, statins exert cardioprotective effects. High-dose statin treatment seems to reduce cardiovascular complications in high-risk patients. The ideal timing and administration regime remain unknown. ObjectivesThis study compared the cardioprotective effects of intravenous statin administration during myocardial infarction (MI) with oral administration immediately post-MI. MethodsHypercholesterolemic pigs underwent MI induction (90 min of ischemia) and were kept for 42 days. Animals were distributed in 3 arms (A): A1 received an intravenous bolus of atorvastatin during MI; A2 received an intravenous bolus of vehicle during MI; and A3 received oral atorvastatin within 2 h post-MI. A1 and A3 remained on daily oral atorvastatin for the following 42 days. Cardiac magnetic resonance analysis (days 3 and 42 post-MI) and molecular/histological studies were performed. ResultsAt day 3, A1 showed a 10% reduction in infarct size compared with A3 and A2 and a 50% increase in myocardial salvage. At day 42, both A1 and A3 showed a significant decrease in scar size versus A2; however, A1 showed a further 24% reduction versus A3. Functional analyses revealed improved systolic performance in A1 compared with A2 and less wall motion abnormalities in the jeopardized myocardium versus both groups at day 42. A1 showed enhanced collagen content and AMP-activated protein kinase activation in the scar, increased vessel density in the penumbra, higher tumor necrosis factor α plasma levels and lower peripheral blood mononuclear cell activation versus both groups. ConclusionsIntravenous administration of atorvastatin during MI limits cardiac damage, improves cardiac function, and mitigates remodeling to a larger extent than when administered orally shortly after reperfusion. This therapeutic approach deserves to be investigated in ST-segment elevation MI patients.

Reversing UVB-induced photoaging with Hibiscus sabdariffa calyx aqueous extract.

Hibiscus sabdariffa is commonly used in daily life and its extract is applied widely in food and cosmetics. However, it has not been evaluated for its anti-aging effects. Hibiscus sabdariffa calyx aqueous extract (HSCAE) has shown potential collagenase activity suppression effects, together with tyrosinase activity inhibition, and anti-oxidation as a free radical scavenger. The current investigation demonstrated that HSCAE was not cytotoxic in skin fibroblasts, and it significantly decreased ultraviolet B (UVB)-induced reactive oxygen species (ROS) on a flow cytometry assay. Moreover, HSCAE reduced matrix metalloproteinase (MMP) expression, increased tissue inhibition of metalloproteinase (TIMP)-1 level, and enhanced collagen content by inhibiting collagenase activity. It also blocked mRNA and protein expressions of melanin production pathway key factors, including the microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP-1), and dopachrome tautomerase-2 (TRP-2). These results demonstrated, for the first time, the potential of HSCAE as a natural antioxidant with the ability to maintain collagen production and to decrease melanin syntheses under UVB radiation, for anti-aging effects. © 2019 Society of Chemical Industry.

Antiaging and smoothness-improving properties of farnesol-based facial masks on rat skin exposed to ultraviolet B.

Farnesol is an acyclic sesquiterpene presents in various natural sources including fruits, vegetables, and herbs. In this study, we successfully prepared a farnesol-containing gel with ultraviolet B-screening and skin-repairing capabilities. Furthermore, the advantageous potential of farnesol-containing facial masks for UVB-caused sunburnt skin was evaluated. Thus, the objectives of this study are to design and prepare optimal facial masks possessing collagen production and smoothness-enhancing capabilities for the skin. A series of formulations consisting of hydroxypropyl methylcellulose, hyaluronan, and farnesol were used to prepare the facial masks. The effects of the facial masks on collagen production by skin fibroblasts in vitro were examined. The effects of the prepared masks on collagen synthesis, smoothness, and inflammation of the skin were further evaluated in vivo using two modes (mask administration interspersed with UVB exposure and mask administration after UVB exposure) of a rat model. Facial masks containing both 0.3 and 0.8mM farnesol improved skin smoothness and enhanced collagen content and arrangement in the skin of rats with mask administration interspersed with and after UVB exposure. The masks containing 0.8mM farnesol exerted the greatest effects on collagen production/arrangement and smoothness improvement in vivo model. Histopathologically observed inflammation was alleviated, and interleukin (IL)-6 was decreased in the 0.8mM farnesol-containing facial mask-covered skin compared with that without facial masks. The farnesol-containing facial masks prepared in this study may have collagen production-increasing, smoothness-improving, and anti-inflammatory properties for UVB-caused sunburn; thus, farnesol is potentially a beneficial component in facial masks.

B- and T-lymphocyte attenuator stimulation protects against atherosclerosis by regulating follicular B cells.

The immune system is strongly involved in atherosclerosis and immune regulation generally leads to attenuated atherosclerosis. B- and T-lymphocyte attenuator (BTLA) is a novel co-receptor that negatively regulates the activation of B and T cells; however, there have been no reports of BTLA and its function in atherosclerosis or cardiovascular disease (CVD). We aimed to assess the dominant BTLA expressing leucocyte in CVD patients and to investigate whether BTLA has a functional role in experimental atherosclerosis. We show that BTLA is primarily expressed on B cells in CVD patients and follicular B2 cells in low-density lipoprotein receptor-deficient (Ldlr-/-) mice. We treated Ldlr-/- mice that were fed a western-type diet (WTD) with phosphate-buffered saline, an isotype antibody, or an agonistic BTLA antibody (3C10) for 6 weeks. We report here that the agonistic BTLA antibody significantly attenuated atherosclerosis. This was associated with a strong reduction in follicular B2 cells, while regulatory B and T cells were increased. The BTLA antibody showed similar immunomodulating effects in a progression study in which Ldlr-/- mice were fed a WTD for 10 weeks before receiving antibody treatment. Most importantly, BTLA stimulation enhanced collagen content, a feature of stable lesions, in pre-existing lesions. Stimulation of the BTLA pathway in Ldlr-/- mice reduces initial lesion development and increases collagen content of established lesions, presumably by shifting the balance between atherogenic follicular B cells and atheroprotective B cells and directing CD4+ T cells towards regulatory T cells. We provide the first evidence that BTLA is a very promising target for the treatment of atherosclerosis.

Labisia pumila improves wound healing process in ovariectomized rat model

<p class="Abstract">The purpose of this study was to determine the wound healing effect of Labisia pumila in the ovariectomized rat model. Ninety-nine Sprague Dawley female rats equally divided into nine groups; where five were control groups, and four were treated groups. The dressing was changed daily, starting from the wound induction until complete healing. The percentage of wound contraction was measured on day 0, 2, 5, 8, 9, 10, 11, 12 and 13. Three rats were sacrificed from each group on day 2, 5 and 8 respectively for evaluating of histological assessments. Wounds dressed with extract showed considerable healing and significantly healed faster compared to all control groups (p<0.05). Moreover, histological analysis revealed remarkable reduction in the scar width correlated with the enhanced collagen content and fibroblast cells, accompanied by a reduction of inflammatory cells in the granulation tissues. In conclusion, L. pumila may promote wound healing in postmenopausal rat model.</p><p class="Abstract"><strong>Video Clip of Methodology</strong>:</p><p class="Abstract">Ovariectomy and punch biopsy: 3 min 11 sec: <a href="https://www.youtube.com/v/IlFrHeww5Jo">Full Screen</a> <a href="https://www.youtube.com/watch?v=IlFrHeww5Jo">Alternate</a></p>

Curcuma purpurascens BI. rhizome accelerates rat excisional wound healing: involvement of Hsp70/Bax proteins, antioxidant defense, and angiogenesis activity.

PurposeCurcuma purpurascens BI. is a member of Zingiberaceae family. The purpose of this study is to investigate the wound healing properties of hexane extract of C. purpurascens rhizome (HECP) against excisional wound healing in rats.Materials and methodsTwenty four rats were randomly divided into 4 groups: A) negative control (blank placebo, acacia gum), B) low dose of HECP, C) high dose of HECP, and D) positive control, with 6 rats in each group. Full-thickness incisions (approximately 2.00 cm) were made on the neck area of each rat. Groups 1–4 were treated two-times a day for 20 days with blank placebo, HECP (100 mg/kg), HECP (200 mg/kg), and intrasite gel as a positive control, respectively. After 20 days, hematoxylin and eosin and Masson’s trichrome stainings were employed to investigate the histopathological alterations. Protein expressions of Bax and Hsp70 were examined in the wound tissues using immunohistochemistry analysis. In addition, levels of enzymatic antioxidants and malondialdehyde representing lipid peroxidation were measured in wound tissue homogenates.ResultsMacroscopic evaluation of wounds showed conspicuous elevation in wound contraction after topical administration of HECP at both doses. Moreover, histopathological analysis revealed noteworthy reduction in the scar width correlated with the enhanced collagen content and fibroblast cells, accompanied by a reduction of inflammatory cells in the granulation tissues. At the molecular level, HECP facilitates wound-healing process by downregulating Bax and upregulating Hsp70 protein at the wound site. The formation of new blood vessel was observed in Masson’s trichrome staining of wounds treated with HECP (100 and 200 mg/kg). In addition, HECP administration caused a significant surge in enzymatic antioxidant activities and a decline in lipid peroxidation.ConclusionThese findings suggested that HECP accelerated wound-healing process in rats via antioxidant activity, angiogenesis effect and anti-inflammatory responses involving Hsp70/Bax.

The exercise-induced biochemical milieu enhances collagen content and tensile strength of engineered ligaments.

Exercise stimulates a dramatic change in the concentration of circulating hormones, such as growth hormone (GH), but the biological functions of this response are unclear. Pharmacological GH administration stimulates collagen synthesis; however, whether the post-exercise systemic milieu has a similar action is unknown. We aimed to determine whether the collagen content and tensile strength of tissue-engineered ligaments is enhanced by serum obtained post-exercise. Primary cells from a human anterior cruciate ligament (ACL) were used to engineer ligament constructs in vitro. Blood obtained from 12 healthy young men 15 min after resistance exercise contained GH concentrations that were ∼7-fold greater than resting serum (P < 0.001), whereas IGF-1 was not elevated at this time point (P = 0.21 vs. rest). Ligament constructs were treated for 7 days with medium supplemented with serum obtained at rest (RestTx) or 15 min post-exercise (ExTx), before tensile testing and collagen content analysis. Compared with RestTx, ExTx enhanced collagen content (+19%; 181 ± 33 vs. 215 ± 40 μg per construct P = 0.001) and ligament mechanical properties - maximal tensile load (+17%, P = 0.03 vs. RestTx) and ultimate tensile strength (+10%, P = 0.15 vs. RestTx). In a separate set of engineered ligaments, recombinant IGF-1, but not GH, enhanced collagen content and mechanics. Bioassays in 2D culture revealed that acute treatment with post-exercise serum activated mTORC1 and ERK1/2. In conclusion, the post-exercise biochemical milieu, but not recombinant GH, enhances collagen content and tensile strength of engineered ligaments, in association with mTORC1 and ERK1/2 activation.

Synergistic effect of collagen-based glucophage-loaded biodegradable nanofibrous membranes with largely enhanced collagen content for accelerating diabetic wound repair

Synergistic effect of collagen-based glucophage-loaded biodegradable nanofibrous membranes with largely enhanced collagen content for accelerating diabetic wound repair

Scaffold-free cartilage subjected to frictional shear stress demonstrates damage by cracking and surface peeling.

Scaffold-free engineered cartilage is being explored as a treatment for osteoarthritis. In this study, frictional shear stress was applied to determine the friction and damage behaviour of scaffold-free engineered cartilage, and tissue composition was investigated as it related to damage. Scaffold-free engineered cartilage frictional shear stress was found to exhibit a time-varying response similar to that of native cartilage. However, damage occurred that was not seen in native cartilage, manifesting primarily as tearing through the central plane of the constructs. In engineered cartilage, cells occupied a significantly larger portion of the tissue in the central region where damage was most prominent (18 ± 3% of tissue was comprised of cells in the central region vs 5 ± 1% in the peripheral region; p < 0.0001). In native cartilage, cells comprised 1-4% of tissue for all regions. Average bulk cellularity of engineered cartilage was also greater (68 × 103 ± 4 × 103 vs 52 × 103 ± 22 × 103 cells/mg), although this difference was not significant. Bulk tissue comparisons showed significant differences between engineered and native cartilage in hydroxyproline content (8 ± 2 vs 45 ± 3 µg HYP/mg dry weight), solid content (12.5 ± 0.4% vs 17.9 ± 1.2%), shear modulus (0.06 ± 0.02 vs 0.15 ± 0.07 MPa) and aggregate modulus (0.12 ± 0.03 vs 0.32 ± 0.14 MPa), respectively. These data indicate that enhanced collagen content and more uniform extracellular matrix distribution are necessary to reduce damage susceptibility. Copyright © 2014 John Wiley & Sons, Ltd.

Topical application of serine proteases from Wrightia tinctoria R. Br. (Apocyanaceae) latex augments healing of experimentally induced excision wound in mice

Ethnopharmacological relevanceWrightia tinctoria R. Br. (Apocyanaceae) is a folk medicinal plant known to have immunomodulatory, anti-inflammatory and antihemorrhagic potential. Wrightia tinctoria latex is used for treatment of various clinical conditions including psoriasis, blisters, mouth ulcers, and extensively for topical application on fresh wounds to promote accelerated healing. Aims of the studyTo investigate the wound healing potential of Wrightia tinctoria latex proteases using a mouse model. Materials and methodsProteolytic activity of Wrightia tinctoria latex proteases (WTLP) was determined on various substrates (casein, gelatin and collagen (type-I and IV)). The thermal stability and the class of proteases present in WTLP were determined using heat treatment and specific protease inhibitors, respectively. Excision wound model in mice was used to evaluate the healing potential of WTLP application (twice daily, 10mg/kg). Neosporin, a standard drug, was used for comparison. The progression of healing was monitored using physical (wound contraction), biochemical (collagen content, catalase and MMP activity) and histological examinations. ResultsWTLP contains thermostable serine proteases, which are completely inhibited by PMSF. WTLP showed strong caseinolytic, gelatinolytic and collagenolytic activity. The excision wound healing rate upon WTLP treatment was significantly higher than (>2-fold) the control group (49% vs. 18%, ⁎⁎p<0.01) on day 3 and throughout the study. PMSF pre-treated and heat denatured WTLP failed to promote wound healing. In addition, serial biochemical analysis of the granulation tissue demonstrated 1.5-fold more (2444±100 vs. 1579±121µg/100mg tissue) hydroxyproline content and 5.6-fold higher catalase activity (16.7±1.3 vs. 3±0.3 units/mg) compared to controls. Further, the enhanced collagen content and matrix metalloproteinase activity correlated with wound contraction rate following WTLP and Neosporin treatment. Histological analysis on day 9 confirmed complete epithelialization, re-establishment of skin structure and accelerated wound healing following WTLP treatment. ConclusionsThe thermostable serine proteases of Wrightia tinctoria latex are directly involved in the wound healing process. Our findings provide a biochemical basis for the role of WTLP in the enhancement of wound healing. The study supports traditional topical application of Wrightia tinctoria latex on fresh wounds to promote accelerated healing.

Maternal Obesity Enhances Collagen Accumulation and Cross-Linking in Skeletal Muscle of Ovine Offspring

Maternal obesity (MO) has harmful effects on both fetal development and subsequent offspring health. We previously demonstrated that MO enhances collagen accumulation in fetal skeletal muscle, but its impact on mature offspring muscle collagen accumulation is unknown. Ewes were fed either a control diet (Con, fed 100% of NRC nutrient recommendations) or obesogenic diet (OB, fed 150% of NRC nutrient recommendations) from 60 days before conception to birth. All ewes received the Con diet during lactation. Male offspring were euthanized at 2.5 years (mean) and the left Longissimus dorsi (LD) muscle and semitendinosus (ST) muscle were sampled. Collagen concentration increased by 37.8±19.0% (P<0.05) in LD and 31.2±16.0% (P<0.05) in ST muscle of OB compared to Con offspring muscle. Mature collagen cross-linking (pyridinoline concentration) was increased for 22.3±7.4% and 36.3±9.9% (P<0.05) in LD and ST muscle of OB group respectively. Expression of lysyl oxidase, lysyl hydroxylase-2b (LH2b) and prolyl 4-hydroxylase (P4HA) was higher in OB LD and ST muscle. In addition, the expression of metalloproteinases (MMPs) was lower but tissue inhibitor of metalloproteinases (TIMPs) was higher in OB offspring muscle, indicating reduced collagen remodeling. MO enhanced collagen content and cross-linking in offspring muscle, which might be partially due to reduced collagen remodeling. Our observation that the collagen content and cross-linking are enhanced in MO offspring muscle is significant, because fibrosis is known to impair muscle functions and is a hallmark of muscle aging.

Nandrolone and resistance training induce heart remodeling: Role of fetal genes and implications for cardiac pathophysiology

AimsThis study was conducted to assess the isolated and combined effects of nandrolone and resistance training on cardiac morphology, function, and mRNA expression of pathological cardiac hypertrophy markers. Main methodsWistar rats were randomly divided into four groups and submitted to 6weeks of treatment with nandrolone and/or resistance training. Cardiac parameters were determined by echocardiography. Heart was analyzed for collagen infiltration. Real-time RT-PCR was used to assess the pathological cardiac hypertrophy markers. Key findingsBoth resistance training and nandrolone induced cardiac hypertrophy. Nandrolone increased the cardiac collagen content, and reduced the cardiac index in non-trained and trained groups, when compared with the respective vehicle-treated groups. Nandrolone reduced the ratio of maximum early to late transmitral flow velocity in non-trained and trained groups, when compared with the respective vehicle-treated groups. Nandrolone reduced the alpha-myosin heavy chain gene expression in both non-trained and trained groups, when compared with the respective vehicle-treated groups. Training reduced the beta-myosin heavy chain gene expression in the groups treated with vehicle and nandrolone. Only the association between training and nandrolone increased the expression of the skeletal alpha-actin gene and atrial natriuretic peptide in the left ventricle. SignificanceThis study indicated that nandrolone, whether associated with resistance training or not, induces cardiac hypertrophy, which is associated with enhanced collagen content, re-expression of fetal genes the in left ventricle, and impaired diastolic and systolic function.

Modulation of liver fibrosis and pathophysiological changes in mice infected with Mesocestoides corti (M. vogae) after administration of glucan and liposomized glucan in combination with vitamin C.

The effects of glucan and liposomized glucan, alone or co-administered with vitamin C, and empty liposomes on hepatic fibrosis in mice infected with Mesocestoides corti (M. vogae) tetrathyridia were studied. Preparations were administered every third day from day 7 to day 31 post-infection (p.i.), nine doses in total. Activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and cholesterol levels were measured in sera collected on days 11, 15, 21, 28, 32, 42, 50 and 65 p.i. Liver fibrosis was studied on the same days by measuring hydroxyproline concentration, which is considered a marker for collagen content. Larvicidal effects of the glucan and liposome preparations were estimated on day 65 p.i. in the liver and peritoneal cavity. Glucan formulations significantly enhanced collagen content, most prominently after administration of liposomized glucan in combination with vitamin C. Activities of both enzymes and cholesterol levels were slightly modified after administration of glucan alone. Liposomized glucan with vitamin C significantly increased ALT and AST activity and cholesterol levels up to days 28-32 p.i., after which they plateaued or declined. The most pronounced decrease was after administration of liposomized glucan and vitamin C. The same pattern of biochemical parameters in serum was observed after administration of empty liposomes, however, collagen content was not modified significantly. Larval counts in the liver and the peritoneal cavity were significantly reduced after treatment with either glucan formulation, but were unaffected following treatment with empty liposomes. In summary, intense fibrosis in the liver of mice treated with liposomized glucan and vitamin C did not result in the most extensive parenchymal cell injury but, rather in the highest efficacy of treatment. Liposomal lipids were probably utilized in the reparation of the damaged parenchymal cells, while glucan stimulated phagocytic cells.

Collagen content in rat liver after experimentally induced cholestasis followed by choledochojejunostomy and X-irradiation.

The right part of the median lobe of the liver of female Wistar rats was irradiated, 12.5 or 25 Gy, at a field size of 15 x 20 mm. The central part of the irradiated liver lobe was fixed and used for the estimation of the collagen protein ratio by means of the Sirius Red-Fast Green extraction method, immediately, 8, 16 or 32 weeks after irradiation. No significant increase in collagen content could be demonstrated in this time range, both after irradiation at 12.5 Gy and at 25 Gy. Partial hepatectomy according to Higgins led to rapid regrowth of the remaining liver lobes. The right lobe grew out rapidly to replace the median lobe. Two days after partial hepatectomy the right lobe was irradiated at the same field size. Measurement of the collagen protein ratio in this experiment did not show a significant increase 8, 16 or 32 weeks after irradiation. However, the 25 Gy group did not survive long enough to obtain data at 16 or 32 weeks. The animals in this latter experiment suffered from ascites before dying. Experimentally induced cholestasis was obtained by ligation and partial resection of the common bile duct. After two weeks of cholestasis the bile flow was restored by Roux-en-Y choledochojejunostomy. The effect of irradiation 2 days after repair surgery was studied. Without irradiation the collagen protein ratio is increased. Irradiation of the right part of the median lobe led to a relatively enhanced collagen content in this lobe. Our results indicate that radiation itself does not lead to a significantly enhanced degree of fibrosis in the liver. However when an increase in collagen content was induced by cholestasis, the partial "dilution" of enhanced fibrosis as a result of proliferation of liver parenchyma cells following repair surgery was inhibited by irradiation.