Damage In Rat Model Research Articles

Ameliorative effects of Triphala on mucosal damage in rat model of ulcerative colitis

In Ayurvedic practice, Triphala is widely used in gastric problems including constipation, large intestinal inflammation and colitis. The present research was planned to assess the ameliorative effects of Triphala formulations in reducing the magnitude and severity of ulcerative colitis. Triphala formulations prepared by mixing three fruits, Haritaki (Terminalia chebula), Bibhitaki (Terminalia belerica) and Amlaki (Emblica officinalis) in different ratios i.e., 1:1:1 (Triphala equal) and 1:2:4 (Triphala unequal) as per classical references. Wistar albino rats were administered with two ml of acetic acid (4% v/v) in intra-colonic lumen for induction of colitis. The efficacy of Triphala was measured on various parameters namely, in vivo fluid absorption in tied-off colon, ulcer score and colonic mucosal parameters. The degree of alteration in colonic fluid transport was significantly reversed by Triphala equal, Triphala unequal and sulphasalzine as standard drug. Triphala formulations significantly attenuated the nitric oxide (NO), myeloperoxidase (MPO) and lipid peroxidation (malondialdehyde MDA) levels in mucosa of rat colon. Pre-treatment with Triphala unequal formulation attenuated the severity of the colonic macroscopic damage score, histologic injury and counteracted the depletion of glutathione and superoxide dismutase activity hence, reduced the oxidative stress in colonic mucosa. Triphala unequal formulation has better protective effects. Outcomes of the present study reveal the usefulness of Triphala formulations in attenuating the colonic inflammation in experimental-induced ulcerative colitis.

Resolvin D1 attenuates acid-induced DNA damage in esophageal epithelial cells and rat models of acid reflux

The role of resolvin D1 (RvD1) in gastroesophageal reflux disease (GERD) remains largely unknown. Here, we investigated the potential role of RvD1 in acid-induced DNA damage in esophageal epithelial cells, patients with refractory GERD and a rat model of acid reflux. Weak acid exposure induced longer comet tails, reactive oxygen species (ROS) generation, oxidative DNA damage and DNA double-strand breaks (DSBs) in cells and RvD1 (0.1 μM) blocked all these effects. Mechanistic analyses showed that apart from ROS-reducing effects, RvD1 possessed a strong capacity to promote DNA damage repair, augmenting cell cycle checkpoint activity and DSB repair by modulating phosphatase and tensin homolog (PTEN) in cells. We also detected the surface expression of formyl peptide receptor 2 (FPR2), a receptor for RvD1, in the esophageal epithelial cells, and inhibition of FPR2 abrogated the protective effects of RvD1 on cells. Furthermore, a positive correlation between RvD1 and PTEN was observed predominantly in the esophageal epithelium from patients with refractory GERD (r = 0.67, P < 0.05). Additionally, RvD1 administration upregulated PTEN, suppressed DNA DSBs and alleviated microscopic damage in the rat model of gastric reflux. FPR2 gene silencing abolished the therapeutic effects of RvD1 on the rat model. Taken together, RvD1 binding to FPR2 protects the esophageal epithelium from acid reflux-induced DNA damage via a mechanism involving the inhibition of ROS production and facilitation of DSB repair. These findings support RvD1 as a promising approach that may be valuable for the treatment of GERD.

Aqueous fruit pulp extract of Adansonia digitata (L) protects against lead-acetate-induced hepato-renal damage in rat model

BackgroundAdansonia digitata (L) fruit has a multi-purpose function one among many, is the antioxidant activities of the fruit by preventing oxidative stress. The effect of Adansonia digitata (L) fruit on lead-induced liver and kidney damage is not clear. Hence, the study was aimed to assessed the protective role of Adansonia digitata (L) fruits against lead acetate induced changes in the liver and kidney function test parameters and the histology of both organ in experimental rats. The rats were divided into five groups with five rats each. All the rats were administered with respective assigned treatment once daily for 6 weeks. Rats in groups I were administered with just distil water (2 ml/kg). Rats in groups II were administered with lead acetate (30 mg/kg) while rats in groups III–V were administered Adansonia digitatata (L) fruit extract (250 mg/kg and 500 mg/kg) and Succimer (5 mg/kg) respectively, then additionally challenged with lead acetate (30 mg/kg) immediately after. At the end of the administration, the blood serum from the experimental rats were used for biochemical analysis. Then, the the organs such as the liver and kidney collected for histological study.ResultsRats administered with Lead acetate showed an increase in AST, ALP and ALT as well as increase in urea and creatinine level (p < 0.001), when compared with the control group (group I), where as Adansonia digitatata (L) fruit prevented the effect (upsurge of serum, Urea, Creatinine, AST, ALP and ALT) of lead acetate. Rats administer with only Lead acetate revealed marked liver steatosis and the degeneration of the kidney glomerulus. The Adansonia digitatata (L) fruit extract and Succimer prevented the histological liver steatosis, as well as the degeneration of the glomerulus of the kidney cytoarchitecture.ConclusionThe findings in this study suggest that Adansonia digitata fruits extract has a protective potentials against lead acetate induced liver and kidney toxicity by preventing the upsurge of liver function enzymes and kidney function parameters. Hence, Adansonia digitata fruits can serve as a natural plant agent that can prevent hepato-renal toxicity. Therefore, Adansonia digitata holds future prospects in preclinical framework to ameliorate organs toxicity for oral therapeutic applications.

Hepatoprotective Effects of Polysaccharide from Anoectochilus roxburghii (Wall.) Lindl. on Rat Liver Injury Induced by CCl4

PurposeThe polysaccharide of Anoectochilus roxburghii (wall.) Lindl. (ARPS) is one of its important active ingredients. Hepatoprotective effects of ARPS on rat liver injury induced by CCl4 were studied.MethodsARPS was extracted using the ultrasonic method and successfully purified by high-speed counter-current chromatography (HSCCC) with a two-phase aqueous system composed of 12.5% PEG 1000–20% K2HPO4:KH2PO4 (1:1). The HSCCC conditions were optimized, and the structure of ARPS was characterized. The hepatoprotective effects of ARPS against CCl4-induced chronic hepatic injury in SD rats were evaluated.ResultsThe results showed that ARPS was a water-soluble polysaccharide with a molecular weight of 28,518 Da. It was composed of mannose, ribose, glucose, and arabian sugar; its monosaccharide molar ratio was glucose:ribose:arabinose:mannose = 54.24:13.20:1.09:1.00. The purity of ARPS was determined by HPLC to be 96.93%. The intervention effects of ARPS on CCl4-induced hepatic damage model in rats showed that ARPS could effectively reduce the activity of alanine amino transferase and aspartate amino transferase, decrease the content of malondialdehyde and nitric oxide synthesis, and increase the content of glutathione. Pathology revealed that liver plate order, liver cell degeneration, and edema were improved; inflammatory cell infiltration was not observed after ARPS intervention.ConclusionARPS had the function of antioxidant for protecting CCl4-induced injured liver, and the mechanisms were related to anti-lipid peroxidation, which could eliminate oxygen-free radicals and protect liver cells from attacks by free radicals.

Development of Pelubiprofen Tromethamine with Improved Gastrointestinal Safety and Absorption.

Pelubiprofen (PEL), which is a commercialized non-steroidal anti-inflammatory drug (NSAID), is associated with the risk of gastrointestinal (GI) adverse events following long-term exposure and has poor water-soluble properties. Here, a new pelubiprofen tromethamine (PEL-T) with improved solubility, permeability, GI safety, and absorption, compared to PEL, has been developed. The nuclear magnetic resonance spectroscopy (NMR), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR) results confirmed that the PEL-T was well formed. The powder of PEL-T showed the presence of additional 6H protons at δ 3.66–3.61 in the 1H NMR spectrum, and shifted the sharp endothermic peaks at 129 °C in DSC, and the spectrum of distinct absorption peaks in FT-IR. In addition, compared with PEL, PEL-T showed a significantly improved solubility in various media and an increased permeability coefficient (Kp) in Caco-2 cells. Furthermore, compared to PEL oral administration, PEL-T was found to significantly reduce the damaged area in an acute gastric damage rat model. The pharmacokinetic study of the PEL-T powder showed higher maximum plasma concentration (Cmax) and area under the plasma concentration–time curve from 0 h to the last time point (AUCt) than those of the PEL powder. Taken together, our data suggest that PEL-T is a recommendable candidate with enhanced gastrointestinal safety and better absorption compared with commercial PEL.

Bee Bread Ameliorates Vascular Inflammation and Impaired Vasorelaxation in Obesity-Induced Vascular Damage Rat Model: The Role of eNOS/NO/cGMP-Signaling Pathway.

Obesity and hyperlipidemia are major risk factors for developing vascular diseases. Bee bread (BB) has been reported to exhibit some biological actions, including anti-obesity and anti-hyperlipidemic. This study aims to investigate whether bee bread can ameliorate vascular inflammation and impaired vasorelaxation activity through eNOS/NO/cGMP pathway in obese rats. Forty male Sprague-Dawley rats were randomly divided into four groups (n = 10/group), namely: control (normal group), obese rats (OB group), obese rats treated with bee bread (0.5 g/kg/day, OB/BB group) and obese rats treated with orlistat (10 mg/kg/day, OB/OR group). The latter three groups were given a high-fat diet (HFD) for 6 weeks to induced obesity before being administered with their respective treatments for another 6 weeks. After 12 weeks of the total experimental period, rats in the OB group demonstrated significantly higher Lee obesity index, lipid profile (total cholesterol, triglyceride, low-density lipoprotein), aortic proinflammatory markers (tumor necrosis factor-α, nuclear factor-κβ), aortic structural damage and impairment in vasorelaxation response to acetylcholine (ACh). Bee bread significantly ameliorated the obesity-induced vascular damage manifested by improvements in the lipid profile, aortic inflammatory markers, and the impaired vasorelaxation activity by significantly enhancing nitric oxide release, promoting endothelial nitric oxide synthase (eNOS) and cyclic guanosine monophosphate (cGMP) immunoexpression. These findings suggest that the administration of bee bread ameliorates the impaired vasorelaxation response to ACh by improving eNOS/NO/cGMP-signaling pathway in obese rats, suggesting its vascular therapeutic role.

Renal Tissue Damage Induced by Acute Kidney Injury in Sepsis Rat Model Is Inhibited by Cynaropicrin via IL-1β and TNF-α Down-Regulation.

Acute kidney injury (AKI), one of the frequently diagnosed and serious sepsis induced complication has high morbidity and mortality. The present study investigated the effect of cynaropicrin on AKI induced pathological damage in rat model in vivo. Treatment with cynaropicrin suppressed AKI induced urea nitrogen and creatinine in the rat serum in dose-dependent manner. Development of sepsis mediated renal injury in rats was also effectively prevented on treatment with cynaropicrin. Secretion of AKI-induced IL-1β and TNF-α in renal tissues was alleviated significantly in rats by cynaropicrin treatment. Additionally, in cynaropicrin-treated rats renal tissues AKI induced Bax expression was alleviated while as Bcl-2 was promoted compared to AKI rats. Cynaropicrin treatment improved the survival rate of the rats with AKI. Cynaropicrin inhibits renal tissue damage and increase survival rate in AKI rat model. The mechanism involves alleviation of inflammatory cytokine secretion and promotion of Bcl‑2 expression. Thus, cynaropicrin may be used as therapeutic agent for treatment of AKI.

Suppressive effects of mead acid supplementation on acute liver damage model in rats

Suppressive effects of mead acid supplementation on acute liver damage model in rats

Effect of Resveratrol on Thioacetamide-induced Liver Damage in Rat Models

Background: The current treatments of liver diseases are not sufficiently effective, and there has been no therapy that can successfully prevent liver failure and its complications. Previous studies have suggested that resveratrol could inhibit the progression of hepatic diseases based on its antioxidative and anti-inflammatory potentials. Objectives: The present study evaluated the hepato-protective effects of resveratrol in thioacetamide (TAA)-induced acute liver damage in rats using neurobehavioral and biochemical parameters. Methods: Forty-eight healthy adult Wistar rats were divided into four groups: C1: healthy control group, C2: non-treated liver failure, E1: liver failure treated with resveratrol 5 mg/kg/day, and E2: liver failure treated with resveratrol 10 mg/kg/day. Aspartate aminotransferase/alanine aminotransferase (AST/ALT), alkaline phosphatase (Alk), total bilirubin (TB), and plasma-ammonia (NH4) were analyzed, and histopathological evaluations of the specimens were carried out after sacrificing the models. Hepatic encephalopathy (HE) grading, open-field, elevated plus arms, and forced-swimming tests were performed in the study. Results: The resveratrol-treated groups had lower serum concentrations of NH4, ALT, and AST than the C2 group (P &lt; 0.05). The pathological evaluations demonstrated that resveratrol-treated groups had better outcomes in inflammatory cell infiltration, apoptosis, vacuolization, liver tissue necrosis, and liver damage stage than the C2 group (P &lt; 0.05). They also showed lower grades of HE, higher locomotor activity (open-field test), and diminished levels of depression (forced-swimming) when compared to the C2 group (P &lt; 0.05). Conclusions: Resveratrol supplementation can improve liver damage as AST, ALT, NH4, and tissue damages were decreased after administering the agent in TAA-induced liver damage. Resveratrol can also improve the neurobehavioral manifestations in animal models of liver failure.

Role and Mechanism of Maresin-1 in Acute Lung Injury Induced by Trauma-Hemorrhagic Shock.

BackgroundIt is reported that trauma hemorrhagic shock (THS) could resulted in organ injury and is related to a high mortality rate. Maresin-1 (MaR1), a derived medium through biosynthesis, is involved in inflammatory responses. However, the mechanism of MaR1 against acute lung injury needs to be further understood. This report aimed to explore whether MaR1 had a protective effect on lung injury.Material/MethodsWe constructed a THS-induced acute lung damage rat model and then treated the rats with MaR1. We determined Evan’s blue dye (EBD) lung permeability, lung permeability index, wet/dry (W/D) weight ratio, nitric oxide (NO) concentration and inducible nitric oxide synthase (iNOS) expression in lung tissue samples. The inflammation-related cytokines levels in the bronchoalveolar lavage fluid (BALF) and serum of rats were determined by enzyme-linked immunosorbent assay (ELISA). Finally, the TLR4/p38MAPK/NF-κB pathway was analyzed by quantitative real-time polymerase chain reaction and western blot assay.ResultsThe increased EBD ratio, lung permeability index and W/D weight ratio, NO concentration and iNOS levels were suppressed by MaR1 treatment. THS-induced over-production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in BALF and serum was suppressed by MaR1. Besides, the TLR4/p38MAPK/NF-κB pathway activation in THS-induced rats were inhibited by MaR1 treatment.ConclusionsOur study showed that MaR1 could effectively alleviated THS-induced lung injury via inhibiting the excitation of the TLR4/p38MAPK/NF-κB pathway in THS-induced rats, suggesting that MaR1 might be a novel agent for lung damage treatment.

The Therapeutic Potential of Extracellular Vesicles Versus Mesenchymal Stem Cells in Liver Damage.

The extracellular vesicles (EVs) secreted by bone marrow-derived mesenchymal stem cells (MSCs) hold significant potential as a novel alternative to whole-cell therapy. We herein compare the therapeutic potential of BM-MSCs versus their EVs (MSC-EVs) in an experimental Carbon tetrachloride (CCl4)-induced liver damage rat model. Rats with liver damage received a single IV injection of MSC-EVs, 1 million MSCs, or 3 million MSCs. The therapeutic efficacy of each treatment was assessed using liver histopathology, liver function tests and immunohistochemistry for liver fibrosis and hepatocellular injury. Animals that received an injection of either MSCs-EVs or 3 million MSCs depicted significant regression of collagen deposition in the liver tissue and marked attenuation of hepatocellular damage, both structurally and functionally. Similar to high doses of MSC-based therapy (3 million MSCs), MSC-EVs mitigated the fibrogenesis and hepatocellular injury in a rat model of CCl4-induced liver fibrosis. The anti-fibrinogenic effect was induced by attenuating hepatic stellate cell activation. Therefore, the administration of MSC-EVs could be considered as a candidate cell-free therapeutic strategy for liver fibrosis and hepatocellular damage.

CD41-deficient exosomes from non-traumatic femoral head necrosis tissues impair osteogenic differentiation and migration of mesenchymal stem cells

Non-traumatic osteonecrosis of the femoral head (ONFH) is clinically a devastating and progressive disease without an effective treatment. Mesenchymal stem cells (MSCs) transplantation has been used to treat ONFH in early stage, but the failure rate of this therapy is high due to the reduced osteogenic differentiation and migration of the transplanted MSCs related with pathological bone tissues. However, the mechanism responsible for this decrease is still unclear. Therefore, we assume that the implanted MSCs might be influenced by signals delivered from pathological bone tissue, where the exosomes might play a critical role in this delivery. This study showed that exosomes from ONFH bone tissues (ONFH-exos) were able to induce GC-induced ONFH-like damage, in vivo and impair osteogenic differentiation and migration of MSCs, in vitro. Then, we analyzed the differentially expressed proteins (DEPs) in ONFH-exos using proteomic technology and identified 842 differentially expressed proteins (DEPs). On the basis of gene ontology (GO) enrichment analysis of DEPs, fold-changes and previous report, cell adhesion-related CD41 (integrin α2b) was selected for further investigation. Our study showed that the CD41 (integrin α2b) was distinctly decreased in ONFH-exos, compared to NOR-exos, and downregulation of CD41 could impair osteogenic differentiation and migration of the MSCs, where CD41-integrin β3-FAK-Akt-Runx2 pathway was involved. Finally, our study further suggested that CD41-affluent NOR-exos could restore the glucocorticoid-induced decline of osteogenic differentiation and migration in MSCs, and prevent GC-induced ONFH-like damage in rat models. Taken together, our study results revealed that in the progress of ONFH, exosomes from the pathological bone brought about the failure of MSCs repairing the necrotic bone for lack of some critical proteins, like integrin CD41, and prompted the progression of experimentally induced ONFH-like status in the rat. CD41 could be considered as the target of early diagnosis and therapy in ONFH.

Light and Electron Microscopic Studies on the Possible Protective Effect of Ginger on the Gastric Fundic Mucosa of Adult Male Albino Rats Treated with 5- Fluorouracil

Introduction: 5-fluorouracil is a potent antimetabolite chemotherapeutic medication used for treatment of various malignancies . Using this agent result in toxic effect mainly in the lining of digestive tract. To ameliorate 5 FU toxic effect ginger was implicated in this study.Aim of the Work: To evaluate the microscopic effect of 5-fluorouracil on gastric fundus mucosa in rat models . and to study the possible beneficial role of ginger in the ameliorations of these changes. Material and Methods: Forty-eight adult male albino rates were divided into four groups: group I (control), group II received ginger orally in a dose of 200 mg/kg/day , group III received 5-fluorouracil (15 mg/kg) intraperitoneally and group IV received 5 FU and Ginger as previous doses for 5 days. The fundic part of stomach was excised and subjected to light and electron microscopic studies.Results: In 5 FU treated group, the fundic gastric mucosa showed multiple areas of tissue loss , congested dilated blood vessels and extravasated red blood cells and mononuclear infiltration were seen between fundic gland cells. Parietal cells showed ballooned appearance, vacuolated cytoplasm, and pykontic nuclei. PAS/ Alcian blue stained sections showed marked reduction in both alcian blue and PAS positive reaction. There was strong positive cytoplasmic reaction in the apical and middle parts of the fundic glands for caspase 3 while large number of parietal cells were stained positive for Cox 2. These histological findings were improved after ginger administration. Histomorphometric study revealed significant weight reduction, increased mucosal ulcer depth, decreased mucosal thickness and increased number of parietal cells in 5 FU treated group when compared to control group. Conclusion: 5FU causes gastric damage in rat model. Ginger supplementation could be used to alleviate the damaging pathological effect on gastric fundus.

Neuroprotective effect of organic and inorganically grown tea on oxidative damage in rat model of Alzheimer’s disease

Production of improved valued tea is in high demand due to its pharmacological properties against various neurodegenerative diseases like Alzheimer’s disease. In this study, an attempt was made to compare the protective effect of the tea grown under organic and inorganic nutrient management practices against intra-cerebroventricular (i.c.v) colchicine induced memory impairment and oxidative damage in rat model of Alzheimer’s disease (AD). Results showed that chronic intraperitoneal (i.p) administration of tea extract (20 mg/kg i.p) significantly improved the cognitive dysfunction and memory impairment in colchicine treated AD rat model. This beneficial effect occurred with an increase in α-secretase activity, Superoxide dismutase, Catalase activities, and a decrease in Acetylcholinesterase level, Aβ -42 level, Cox-2-linked neuro-inflammation by intraperitoneal injection of tea extract grown organically and inorganically. The amyloid Aβ concentration in the rat model of AD was 84 ± 1.7 pg/mg protein. With administration of tea extract, the amyloid Aβ concentration decreased significantly to 55 ± 1.5, 52 ± 1.3 and 49 ± 1.5 pg/mg protein with the field level management of inorganic, integrated and organic nutrients, respectively. In this study celecoxib (20 mg/kg i.p) is used as a reference standard. This study stated organic tea as a promising neuroprotective agent or adjuvant to prevent AD.

Hepatoprotective effect of a fucoidan extract from Sargassum fluitans Borgesen against CCl4-induced toxicity in rats

The in vivo antifibrotic effect of a fucoidan extract (FE) from Sargassum fluitans Borgesen was evaluated in a carbon tetrachloride-induced liver damage model in rats over twelve weeks. Chemical analysis showed the FE to contain carbohydrates, sulfates, uronic acids, protein, phenols, and to have a molecular weight of ~60 kDa. Physiological, biochemical, histological and genetic assays were done. Daily oral administration of FE (50 mg/kg) reduced liver enzymatic activity, liver infiltration of inflammatory cells, collagen fiber deposition and gene expression cytokines such as interleukin beta 1 (IL-β1), tumor necrosis factor alpha (TNF-α), transforming growth factor beta 1 (TGF-β1), Smad-3, Smad-2, collagen 1 alpha 1 (col1α1) and tissue inhibitor of metalloproteinase 1 (TIMP-1). It also increased RNA expression of Smad-7 and metalloproteinase 2 and 9 (MMP2 and MMP9). The fucoidan extract exhibited an antifibrotic effect mediated by the inhibiting TGF-β1/Smad pathway, as well as anti-inflammatory effects.

The long term effects of intrascrotal low dose and high dose N-acetylcysteine on testis damage in rat model of testicular torsion

Background/PurposeDuring testicular torsion, the testes face oxidative damage owing to ischemia/reperfusion. We studied the long term effects of the intrascrotal administration of N-acetylcysteine (NAC) during detorsion procedure in a rat model of testicular torsion. MethodsTwenty-eight rats were divided into 4 groups: (1) Control group: No procedure was done (2): Torsion–detorsion group: Testis torsion applied for 3 h (3): Low Dose Group: After testis torsion–detorsion (for 3 h) 10 mg/kg NAC was given into tunica vaginalis (4): High Dose Group: After testis torsion–detorsion (for 3 h) 100 mg/kg NAC was given into tunica vaginalis. We measured dimensions of the testes and examined pathological findings and Johnsen and Cosantino Scores. ResultsFor testes height and volume, high dose NAC group had better results than the torsion–detorsion group (p = 0.019, p = 0.049). Testes weight showed no difference (p = 0.204). Sertoli cell number per tubule in the high dose NAC group was statistically different than the torsion–detorsion group (p = 0.017). ConclusionsWhen NAC was given intrascrotally at a dose of 100 mg/kg, it decreased the loss of testis volume and height, and Sertoli cell number per tubule was similar to the control group. These results suggest that the higher dose intrascrotal NAC administered during detorsion may have a protective effect.

Olive-Derived Hydroxytyrosol Shows Anti-inflammatory Effect without Gastric Damage in Rats.

Hydroxytyrosol (HT) is a simple phenol compound present in olive oil. In a previous in vitro study, we showed that HT downregulated lipopolysaccharide-mediated expression of inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), tumor necrosis factor alpha, and interleukin-1β, resulting in reduced nitric oxide and prostaglandin E2 production. In the present study, we aimed to determine whether HT suppresses COX-2-induced inflammation in a carrageenan-induced rat paw edema model. Additionally, we compared its activity with those of the selective COX-2 inhibitor, celecoxib for a comparative control, and a representative nonsteroidal anti-inflammatory drug (NSAID), indomethacin for a positive control. HT, celecoxib, and indomethacin significantly suppressed swelling in carrageenan-injected rat paws. Although HT was less effective than celecoxib and indomethacin, it had a delayed onset of action. Moreover, we evaluated whether HT aggravates gastric damage, which is a typical adverse effect associated with NSAIDs and COX-2 inhibitors under low dose aspirin (LDA) treatment, in an aspirin-induced gastric damage rat model. Unlike celecoxib and indomethacin, HT did not cause gastric damage when co-administered with aspirin. Our results indicate that HT exerts a delayed but sustained anti-inflammatory effect against COX-2-mediated inflammation. Finally, the combination of short-acting conventional anti-inflammatory drugs and long-acting HT can be considered a new, safe, and effective anti-inflammatory treatment modality even when continuously administered for a long period under LDA treatment.

Hepato-protective effects of Glossogyne tenuifolia in Streptozotocin-nicotinamide-induced diabetic rats on high fat diet

BackgroundGlossogyne tenuifolia (GT) is a traditional herbal tea in Penghu Island, Taiwan. Its extract is traditionally been used as an antipyretic, hepatoprotective and anti-inflammatory remedy in folk medicine among local residents. The present study investigated whether GT could improve streptozotocin-induced acute liver injury of type 2 diabetes mellitus.MethodsMale Wistar rats aged eight weeks were induced to be hyperglycemic by the subcutaneous injection of streptozotocin-nicotinamide (STZ-NA) and a combination of a high-fat diet (HFD) (N group). The animals were given GT extracts at a low dose (50 mg/kg) (L group) or a high dose (150 mg/kg) (H group) or an anti-diabetic drug (acarbose) (P group) in drinking water for 4 weeks.ResultsThe results revealed that STZ-NA increased hepatomegaly, hepatocyte cross-sectional area, hypertrophy-related pathways (IL6/STAT3-MEK5-ERK5, NFATc3, p38 and JNK MAPK), proapoptotic molecules (cytochrome C, cleaved caspase-3), and fibrosis-related pathways (FGF-2, pERK1/2). These pathway components were then expressed at lower levels in the L and H group when compared with the N group. The liver-protective effect of GT in STZ-NA-induced diabetic rats with hyperlipidemia was through an enhancement in the activation of the compensatory PI3K-Akt and Bcl2 survival-related pathway.ConclusionThe results demonstrate that the hot water extracts of GT efficiently ameliorates the STZ-NA-induced diabetes associated liver damage in rat models.

Neuroprotective effect of neuregulin-1β on spinal cord ischemia reperfusion injury

Objective: This study was designed to see if neuregulin-1β (NRG-1β) plays a protective role in spinal cord ischemia and reperfusion injury (SCII). Design: Animal research. Setting: China. Participants: NA. Interventions: Forty-eight SD rats were randomly divided into control group (n = 16), SCII model group (n = 16) and NRG-1β-treated group (n = 16). In control group, the abdominal aorta was isolated but not clipped. The rats in NRG-1β-treated group were treated with 10μg/kg NRG-1β during developing SCII model. Outcome Measures: Neurological scores were evaluated. At 3, 6, 12 and 24 h after the reperfusion, rats were killed. Pathological changes of spinal cord were assessed with HE staining, and immunohistochemical staining of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). MMP-9 and TIMP-1 mRNA levels were assessed using real-time PCR. Results: NRG-1β reduced the damage of SCII in the rats. The expression of MMP-9 protein and mRNA in NRG-1β treatment group was significantly lower than the model group (P < 0.05) at 6 h, 12 h and 24 h after the perfusion. The expression of TIMP-1 protein and mRNA in the treatment group was significantly higher than the model group at 12 h and 24 h after the perfusion. Conclusion: NRG-1β reduced the reperfusion damage in rat model of SCII, in which process MMP-9 and TIMP-1 were probably involved.

Two methods for modeling of sick sinus syndrome in rats: Ischemia reperfusion and sodium hydroxide induced injury

The Sick Sinus Syndrome (SSS) is a serious life-threatening heart disease. It is important to establish a credible and stable sinus node damage model. In this study, we use two methods to construct an SSS damage model in rats. One is to inject sodium hydroxide to the SSS area through internal jugular vein. Another is to cause ischemia-reperfusion injury on the SSS area. 43 healthy SD rats were randomly divided into 4 groups, namely ischemia-reperfusion injury group (IRIG), inject sodium hydroxide group (ISHG), and propranolol group (PG) and the control group (CG). The achievement ratio of modeling was 67% in the IRIG and 83% in the ISHG. The HR significantly decreased after operation in the IRIG and ISHG compared with pre-operation (P＜0.01). The HR was reduced by above 30% in these 2 groups after modeling, while the reduction was better maintained in IRIG. Additionally, the sinoatrial node recovery time (SNRT) and sinoatrial conduction time (SACT) were significantly prolonged compared with pre-modeling in 2 groups (P < 0.01). Morphology results showed blurry in structure and boundaries with pale cytoplasm. It is speculated that IRIG and ISHG modeling might influence the calcium concentration and damage the sinus node function by decrease the expression of HCN4 and SCN5A, which impaired the driving ability of sinus node and leading to apoptosis. Ischemia reperfusion injury and sodium hydroxide injury could construct stable SSS models which could represent clinic pathological damage. Thus, both methods could be used for further studies of the SSS mechanisms and drugs.