Alcoholic Rats Research Articles

Possible involvement of Protein Tyrosine Phosphatase in Alcoholic Cardiomyopathy

Protein tyrosine phosphatases (PTPase’s) are the enzymes that dephosphorylate survival kinase PI3K/Akt pathway this may be a key mechanism in alcohol-induced cardiomyopathy. Therefore, the present study was designed to investigate the role of PTPase in alcohol-induced cardiomyopathy. Ethanol (20%) at the dose of 7.9 g/kg P.o was given regularly for 60 days that produced Alcohol-induced Cardiomyopathy (ACM). CM (cardiomyopathy) was assessed in terms of decrease in LVDP, dp/dtmax, dp/dtmin, LV protein content, CFR and increase in LVEDP, LVW/BW, MABP, LV collagen, LV cholesterol content, TNF-α, nitrite levels and iNOS expression in alcoholic cardiomyopathic rats. Sodium Orthovanadate (SOV) (PTPase inhibitor) at the dose of 2.5, 5 and 10mg/kg significantly increased LVDP, dp/dtmax, dp/dtmin, CFR, LV protein content. Moreover, significant decrease in the elevated MABP, LVEDP, LVW/BW, LV collagen, LV cholesterol content, nitrite, TNF-α and iNOS level was observed. Furthermore, administration of SMT (S-methylisothiourea), an iNOS inhibitor (5mg/kg., i.p) with SOV (10mg/kg., p.o) significantly increased the ameliorative effect of SOV (10mg/kg., p.o). The findings suggested that PTPases may have a function in regulating alcohol-induced cardiomyopathy by interfering with Akt/Pi3k and its downstream pathways, which include TNF-alpha and iNOS.

Protective effects of extracts of forsythia suspensa and chrysanthemum on alcoholic hypertension rats based on tissue pathological slice image analysis

To explore the effects of Forsythia suspensa and Chrysanthemum indicum extracts on blood pressure as well as hepatic and renal functions of hypertensive rats and to optimize the most beneficial combination of the two herbs to achieve this goal. After hypertension was observed, rats were administrated with extracts of F. suspensa and C. indicum by gastric perfusions at doses of 20 mL/kg, for fourteen days. On the fourteenth day, rats were fasted for 12 h and then blood was collected from the eyeballs for serum measurement of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, albumin, total cholesterol, triglycerides, very low density lipoprotein, sodium, potassium and creatinine. Hepatic and renal tissue were harvested and processed into paraffin blocks for observation. F. suspensa and C. indicum at a ratio of 2:1 was the most effective with respect to liver repair in the hypertensive rats (p < 0.05). Both plant extracts decreased serum lipids and creatinine with the ratio of 2:1 of the two extracts being the most beneficial (p < 0.05). A synergistic effect on decreasing blood pressure and protection of the liver was observed in the hypertensive rats when extracts of F. suspensa and C. indicum were administered in combination. F. suspensa and C. indicum at a ratio of 2:1 was the most effective.

Trigonelline, a Fenugreek Bioactive compound protects Heart tissue against alcohol intoxication: An in-vivo study focusing on antioxidant perspective

BackgroundTrigonella foenum-graecum, commonly known as fenugreek and it is used as a spice. It has antioxidant, anti-diabetic, antilipedemic and other pharmocological properties. ObjectivesThe aim of the study was to detect the cardio protective activity of Trigonelline (TG) a bioactive compound of Trigonella foenum-graecum (TF) in alcohol intoxicated rats. Material and methodsThe young wistar strain albino rats are divided in to 5 groups and treatment was given as per the experimental protocol. Antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR), glutathione (GSH), malondialdehyde (MDA) levels are estimated in cardiac tissue of all experimental groups. Cardiac markers creatine kinase-MB (CK-MB), troponin-T (TT), troponin-I (TI), myoglobin (MG) and serum markers alanine transaminase (AAT), aspartate transaminase (AST) and alkaline phosphatase (ALP) are estimated. Free radical scavenging activities like 2,2-diphenylpicrylhydrazyl (DPPH), hydrogen peroxide (H2O2) and hydroxyl radical are estimated in ethanolic extract of Trigonella foenum-graecum. ResultsSOD, CAT, GPx, GR, GSH activities are depleted and MDA, CK-MB, TT, TI, MG and AAT, AST, ALP activities are elevated in alcohol intoxicated rats. Trigonelline supplementation to alcoholic rats for 30 days elevated antioxidant enzymes, depleted MDA, cardiac markers and serum markers in alcohol intoxicated rats. Free radical scavenging assay also reported that Trigonella foenum-graecum possess free radical scavenging activity. Furthermore, our histopathological evidence also proved that TG protected the cardiac tissue from alcohol induced toxicity in all the experimental rats. ConclusionOur study concluded that TG may be useful to the alcoholic and myocardial infarction subjects.

Hepatoprotective effects and mechanisms of l-theanine and epigallocatechin gallate combined intervention in alcoholic fatty liver rats.

Chronic excessive alcohol consumption can lead to alcoholic fatty liver, posing substantial health risks. l-Theanine (LTA) and epigallocatechin gallate (EGCG) in tea exert antioxidant and hepatoprotective effects. However, the combined effects of LTA and EGCG on rats with alcoholic fatty liver, and the underlying mechanisms of such effects, remain unclear. In this study, Sprague Dawley (SD) rats were fed with alcohol for 6 weeks to induce alcoholic fatty liver. Subsequently, for another 6 weeks, the rats were administered LTA (200 mg kg-1 day-1), EGCG (200 mg kg-1 day-1), or a combination of LTA with EGCG (40 mg kg-1 day-1 l-Thea +160 mg kg-1 day-1 EGCG), respectively. The combined use of LTA and EGCG for alcoholic fatty liver disease had more significant effects than their individual administration. This combination reduced the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as the levels of hepatic triglyceride (TG), malondialdehyde (MDA), and reactive oxygen species (ROS) in the rats. The combined intervention also increased hepatic superoxide dismutase (SOD) and glutathione peroxidase activity. Reductions in hepatic fat accumulation and inflammatory responses were observed. The mechanism underlying these effects primarily involved the inhibition of fatty acid synthesis and the alleviation of lipid peroxidation through the downregulation of the mRNA and protein expression of TNF-α, SREBP1c, and CYP2E1 and the upregulation of the mRNA and protein expression of ADH1, ALDH2, Lipin-1, PPARαPPARα, AMPK, and PGC-1α, thereby promoting the oxidative decomposition of fatty acids and reducing the synthesis of cholesterol and glucose. l-Theanine and EGCG appear to be able to alleviate alcoholic fatty liver by modulating lipid metabolism and ameliorating oxidative stress, indicating their potential as natural active ingredients in anti-alcoholic fatty liver food products. © 2024 Society of Chemical Industry.

Study on the pharmacokinetics, tissue distribution and excretion of Penthorum chinense Pursh in normal and acute alcoholic liver injury rats using validated UPLC-MS/MS method

Penthorum chinense Pursh (PCP), as a traditional medicine of Miao nationality in China, is often used for the treatment of various liver diseases. At present, information regarding the in vivo process of PCP is lacking. Herein, a sensitive and robust ultra-performance liquid chromatography tandem with mass spectrometry (UPLC-MS/MS) was developed and validated for the quantification of several components to study their pharmacokinetics, tissues distribution and excretion in normal and acute alcoholic liver injury (ALI) rats. Prepared samples were separated on a Thermo C18 column (4.6 mm × 50 mm, 2.4 μm) using water containing 0.1 % formic acid (A) and acetonitrile (B) as the mobile phase for gradient elution. Negative electrospray ionization was performed using multiple reaction monitoring (MRM) mode for each component. The validated UPLC-MS/MS assay gave good linearity, accuracy, precision, recovery rate, matrix effect and stability. This method was successfully applied to the pharmacokinetics, tissue distribution and excretion in normal and acute ALI rats. There were differences in pharmacokinetic process, tissue distribution and excretion characteristics, indicating that ALI had a significant influence on the in vivo process of PCP in rats. The research provided an experimental basis for the study of PCP quality control and further application in the clinic.

EFFECTS OF CHRONIC MATERNAL ALCOHOLIZATION ON THE CARDIOMYOCYTE CONTRACTILITY IN RAT OFFSPRINGS

The effects of intrauterine alcohol exposure on heart development, specifically the contractile apparatus and myofibril distribution within cardiomyocytes, remain controversial. Aim: This study investigates the postnatal dynamics of myofibril ultrastructure in rat ventricular cardiomyocytes following chronic maternal alcohol exposure. Methods: We analyzed cardiac tissue from offspring of chronically alcoholized rats at various postnatal stages using transmission electron microscopy. Quantitative parameters of cardiomyocyte myofibrils in different ventricular myocardial zones were assessed. Results: Chronic maternal alcohol exposure appeared to inhibit sarcomerogenesis and reduced overall myofibril content in the hearts of newborn offspring. Furthermore, we observed increased myofibril surface area and disrupted spatial orientation in subendocardial left ventricular cardiomyocytes and intramural zones of both ventricles. Even in mature offspring, the myocardial contractile apparatus remained irreversibly damaged, exhibiting reduced myofibril density, increased surface area, and disrupted orientation.

Letter to the editor: A reply to Grahame (2023) commenting on "Alcohol, place conditioning, and male rats: A systematic review of outcome prediction".

Letter to the editor: A reply to Grahame (2023) commenting on "Alcohol, place conditioning, and male rats: A systematic review of outcome prediction".

Voluntary alcohol intake alters the motivation to seek intravenous oxycodone and neuronal activation during the reinstatement of oxycodone and sucrose seeking

Opioid-alcohol polysubstance use is prevalent and worsens treatment outcomes. Here we assessed whether co-consumption of oxycodone and alcohol influence the intake of one another, demand for oxycodone, and the neurocircuitry underlying cue-primed reinstatement of oxycodone-seeking. Male and female rats underwent oxycodone intravenous self-administration (IVSA) with homecage access to alcohol (20% v/v) and/or water immediately after the IVSA session. Next, economic demand for intravenous oxycodone was assessed while access to alcohol and/or water continued. Control rats self-administered sucrose followed by access to alcohol and/or water. Rats underwent a cue-primed reinstatement test and brains were processed for c-fos mRNA expression. While both sexes decreased oxycodone intake if they had access to alcohol, and decreased alcohol intake if they had access to oxycodone, only female oxycodone + alcohol rats exhibited decreased demand elasticity and increased cue-primed reinstatement. Alcohol consumption increased the number of basolateral and central amygdala neurons activated during sucrose and oxycodone reinstatement and the number of ventral and dorsal striatum neurons engaged by sucrose reinstatement. Nucleus accumbens shell dopamine 1 receptor expressing neurons displayed activation patterns consistent with oxycodone reinstatement. Thus, alcohol alters the motivation to seek oxycodone in a sex-dependent manner and the neural circuitry engaged by cue-primed reinstatement of sucrose and oxycodone-seeking.

Mechanism of the Effect of Compound Anoectochilus roxburghii (Wall.) Lindl. Oral Liquid in Treating Alcoholic Rat Liver Injury by Metabolomics.

Compound Anoectochilus roxburghii (Wall.) Lindl oral liquid (CAROL) is often as a hepatoprotective agent. The present study aimed to elucidate the protective mechanism of CAROL against alcoholic liver injury in rats by untargeted metabolomics combined with multivariate statistical analysis. An alcoholic liver disease model was established in sprague-dawley (SD) rats by gavage of alcohol, and CAROL treatment was administered. The hepatoprotective effect of CAROL was evaluated by examining liver tissues changes and detecting biochemical index activities and cytokines in serum and liver homogenates. The metabolites in serum samples were examined using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) and multivariate statistical analysis to screen for differentially expressed metabolites and Kyoto Encyclopedia of Genes and Genomes (KEGG) to assess potential metabolic pathways. CAROL has the potential to downregulate inflammation levels and alleviate oxidative stress. The differential metabolites are mainly engaged in riboflavin metabolism, arginine and proline metabolism, phenylalanine, tyrosine and tryptophan biosynthesis metabolism, phenylalanine metabolism, pyrimidine metabolism, and vitamin B6 metabolism to achieve hepatoprotective effects. CAROL may exhibit beneficial hepatoprotective effects by reducing inflammation, mitigating oxidative stress, and modulating metabolites and their metabolic pathways.This study has important implications for advancing the clinical application of CAROL.

Commentary on "Alcohol, place conditioning, and male rats: A systematic review for outcome prediction".

Commentary on "Alcohol, place conditioning, and male rats: A systematic review for outcome prediction".

The effect of C60 fullerene on the mechanokinetics of muscle gastrocnemius contraction in chronically alcoholized rats

The C60 fullerene effect (oral administration at a dose of 1 mg kg−1) on the selected biomechanical parameters of muscle gastrocnemius contraction, biochemical indicators of blood and muscle tissue as well as histological changes in rat muscle tissue after chronic alcoholization for 3, 6 and 9 months was studied in detail. Water-soluble C60 fullerenes were shown to reduce the pathological processes development in the muscle apparatus by an average of (35–40)%. In particular, they reduced the time occurrence of fatigue processes in muscle during the long-term development of alcoholic myopathy and inhibited oxidative processes in muscle, thereby preventing its degradation. These findings open up the possibility of using C60 fullerenes as potent antioxidants for the correction of the pathological conditions of the muscle system arising from alcohol intoxication.

New biofunctional effects of oleanane-type triterpene saponins.

In the current review, we describe the novel biofunctional effects of oleanane-type triterpene saponins, including elatosides, momordins, senegasaponins, camelliasaponins, and escins, obtained from Aralia elata (bark, root cortex, young shoot), Kochia scoparia (fruit), Polygala senega var. latifolia (roots), Camellia japonica (seeds), and Aesculus hippocastanum (seeds), considering the following biofunctional activities: (1) inhibitory effects on elevated levels of blood alcohol and glucose in alcohol and glucose-loaded rats, respectively, (2) inhibitory effects on gastric emptying in rats and mice, (3) accelerative effects on gastrointestinal transit in mice, and (4) protective effects against gastric mucosal lesions in rats. In addition, we describe (5) suppressive effects of the extract and chakasaponins from Camellia sinensis (flower buds) on obesity based on inhibition of food intake in mice. The active saponins were classified into the following three types: (1) olean-12-en-28-oic acid 3-O-monodesmoside, (2) olean-12-ene 3,28-O-acylated bisdesmoside, and (3) acylated polyhydroxyolean-12-ene 3-O-monodesmoside. Furthermore, common modes of action, such as involvements of capsaicin-sensitive nerves, endogenous NO and PGs, and possibly sympathetic nerves, as well as common structural requirements, were observed. Based on our findings, a common mechanism of action might mediate the pharmacological effects of active saponins. It should be noted that the gastrointestinal tract is an important action site of saponins, and the role of the saponins in the gastrointestinal tract should be carefully considered.

Tiaogan Jiejiu Tongluo Formula attenuated alcohol-induced chronic liver injury by regulating lipid metabolism in rats

Ethnopharmacological relevanceTiaogan Jiejiu Tongluo Formula (TJTF), a traditional Chinese medicine formula, is modified from the well-known ancient prescription Danzhi-Xiaoyao Powder (DXP). Owing to its ability to regulate liver, strengthen spleen, detoxicating, and dredge collaterals in Chinese medicine, TJTF is usually used to treat anxiety, hypertension, alcoholic fatty liver disease in clinical application. However, the protective effect and potential molecular mechanism of TJTF on alcoholic liver injury has not fully been clarified. Aim of the studyTo explore the effect of TJTF on chronic alcoholic liver injury and figure out whether its effects were due to the regulation of lipid metabolism. Material and methods75 male SD rats were divided into the following five groups, control group, EtOH group, TJTF high dose group, TJTF low dose group and silybin group. Then a chronic alcoholic liver injury model was established by increasing concentration of 56% ethanol in rats. The rats in each TJTF group were given the corresponding dose of TJTF, the rats in the silybin group were given silybin, the rats in the control group and the EtOH group were given distilled water by gavage, once a day for 8 consecutive weeks. The components of TJTF were analyzed by UPLC-Q-TOF-MS. Hematoxylin and Eosin (H&E) was used to assess the severity of liver injury. in the pathological examination. Periodic acid-Schiff (PAS) and oil red O staining were used to evaluate the degree of the liver glycogen accumulation and lipid deposition, respectively. The serum ALT, AST, T-CHO, TG, LDL-C, ADH, HDL-C, and ALDH levels as well as liver tissue GSH, MDA, and SOD levels were analyzed in rats. Immunohistochemistry and western blotting were used to detect lipid metabolism-related proteins expressed in rat liver. ResultsTJTF significantly alleviated the chronic liver injury caused by alcohol in rats, and enhanced liver function. TJTF significantly decreased AST, ALT, ADH levels and increased ALDH level of serum, and increased GSH, SOD levels and decreased MDA level of liver tissue. In addition, TJTF significantly decreased the serum T-CHO, TG and LDL-C levels and increased HDL-C level in chronic alcoholic liver injury rats by regulating the expression of lipid metabolism associated proteins including p-LKB1, p-AMPKα, p-ACC, FAS, HMGCR, SREBP-1c, PPARα and CPT-1A. The results of western blot and immunohistochemical staining confirmed that TJTF can inhibit lipid production and promote fatty acid oxidation in the liver tissue of chronic alcoholic liver injury rats by activating the LKB1-AMPKα axis and then downregulating the protein expressions of p-ACC, FAS, HMGCR and SREBP-1c, as well as promoting the protein expressions of PPARα and CPT-1A. Meanwhile, TJTF also increased the glycogen content of liver and alleviated the liver damage. ConclusionAccording to current research, TJTF is effective in treating chronic liver damage induced by alcohol in rats. Additionally, TJTF exhibits the protective benefits by modulating LKB1-AMPKα signal axis, which in turn inhibits the synthesis of lipids and promotes the oxidation of fatty acids.

Biochemical parameters of blood and tissue of the gastrocnemius muscle in chronically alcoholized rats under oral administration of C(60) fullerene aqueous solution

Biochemical indices of blood and tissue of the gastrocnemius muscle chronically alcoholized (for 3, 6 and 9 months) rats were studied. С60 fullerene aqueous solution (C60FAS) was administered orally as a pharmacological agent at a dose of 1 mg/kg daily throughout the experiment in a three routes: 1 h before alcohol intake (preventive regimen), together with alcohol (therapeutic regimen I) and 1 h after alcohol intake (therapeutic regimen II). Creatine phosphokinase (CPK), lactate dehydrogenase (LDH), catalase, superoxide dismutase, glutathione peroxidase (GPx) activity and the level of creatinine, lactate, hydrogen peroxide, reduced glutathione were estimated with clinical diagnostic kits. A pronounced upward trend in creatinine and lactate content, CPK and LDH activity with increasing degree of alcoholic myopathy during experiment was detected. Administration of C60FAS was shown to reduce the biochemical indices of muscle injury and to reduce oxidative processes by maintaining the balance between pro-oxidant and antioxidant systems. The maximum positive effect was observed when C60FAS was administered together with alcohol (therapeutic regimen I). The results indicate on C60 fullerene ability to correct the pathological condition of the muscular system arising from alcohol intoxication. Keywords: alcohol intoxication, antioxidant system, C60 fullerene, creatine phosphokinase, gastrocnemius muscle, lactate dehydrogenase

Gastroprotective Effects of the Aqueous Extract of Finger Citron Pickled Products against Ethanol-Induced Gastric Damage: In Vitro and In Vivo Studies.

Finger citron pickled products (FCPP), as folk remedies, are famous in southern China for protecting gastric mucosa. However, the gastric mucosa protection of FCPP has not been reported yet, and its effective mechanism is unclear. In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. Furthermore, we also investigated the main substances in the aqueous extract that exert gastroprotective activity using a GES-1 scratch test and basic chemical composition analysis. FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. Moreover, FCPP aqueous extract could increase superoxide dismutase (SOD) activity and inhibit malondialdehyde (MDA) content, exhibiting good antioxidant capacity. Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. The polysaccharides in FCPP aqueous extract might be the main components that exerted gastroprotective activity, as demonstrated by GES-1 cell scratch assay. This study confirmed that FCPP aqueous extract presented promising potential in protecting gastric mucosa and avoiding gastric ulcers, which could provide an experimental basis for further utilizing the medicinal value and developing new products of FCPP.

Alcohol, place conditioning, and male rats: A systematic review for outcome prediction.

Although Place Conditioning (PC) has been used to study the motivational effects of alcohol for almost 50 years, variables and situations in which alcohol induces PC in rats are still unclear, especially for short PC protocols (up to 10 conditioning trials). To predict primary outcomes (namely, conditioning failure, conditioned place aversion (CPA), and conditioned place preference (CPP)) of alcohol-induced PC with male outbred rats. Systematic review: structured search for relevant records in PUBMED and two other sources, eligible articles defined as those conforming to all inclusion criteria, selection of experiments failing all the exclusion criteria, and analysis of procedure-outcome relations according to the background of variables affecting associative learning, alcohol interventions in rats, and PC interventions themselves. We selected 192 experiments (133 short protocols, 27 long protocols, and 32 protocols with alcohol pre-exposure) from 62 articles to compose the review. Rates of conditioning failure are mainly predicted by interactions of alcohol dose and the number of habituation sessions and conditioning trials. Different conditions (housing systems) and characteristics (age and weight) of animals predict different rates of CPA and CPP: higher rates of CPA are predicted by single-housed, older, and heavier animals, while higher rates of CPP are predicted by group-housed, younger, and lighter animals. We recommend settings for CPP induction in short protocols, indicate the predictive analysis has broad consequences (from theoretical to translational ones) for PC in alcohol research, and specify variables needing more accurate investigation (rat sex, age, weight, strain, spatial configuration of the apparatus, and conditioning timetable). This review may improve our comprehension of results of alcohol-induced PC with rats, refining our understanding of the motivator function of alcohol and the alcohol-seeking behavior triggered by environmental contexts, and opening new research venues on their neurobiological basis.

C60 fullerene reduces the level of fluctuations in the force response of muscle gastrocnemius in chronically alcoholized rats

C60 fullerene reduces the level of fluctuations in the force response of muscle gastrocnemius in chronically alcoholized rats

Lipid composition and oxidative changes in diabetes and alcoholic diabetes rats

BackgroundThe investigating of study was expected to the lipid composition of diabetes and alcoholic diabetes in plasma and erythrocyte membrane biochemical profile in rats. Diabetic male Wistar Streptozotocin (STZ)-induced rats were used experimental models. Control rats (C) were maintained group I, received glucose (i.e., caloric equivalent), diabetic induced rats (STZ) group II, and group III alcoholic treated and IV diabetic and alcoholic treated rats which received 20 % (v/v) alcohol in water, administered through stomach tube (5 g/kg body weight/day). ResultsSTZ-induced diabetic hepatic damage in rats was observed which leads to the increased plasma lipid peroxidation, nitrate and nitrite levels. Diabetic and administration alcohol rats also suggestively lesser the activities of antioxidants, glutathione peroxidase, glutathione S-transferase, superoxide dismutase, catalase and reduced glutathione when related with control rats (group I). Plasma enzymes are normal levels and renovate the enzymic and non-enzymatic antioxidants level in experimental groups. ConclusionThe present data point out that the nitric oxide scavenging levels increased and may possibly protect and adjacent to oxidative stress and free radicals in diabetic hepatopathy rats and histopathological studies were identified in regular hepatic cortex of Group II, III and IV of animals with diabetes, alcoholic and alcohol-induced diabetes rats.

An Analysis of Khurtsiin Deed-6 Compound’s Effect on IL-1β Expression in Nitroglycerin Induced Migraine and Alcohol Exposed Neurodegeneration Model in Rat

Objectives: To investigate the anti-inflammatory activity of Khurtsiin deed-6 in migraine and neurodegeneration rat models. Methods: This study uses nitroglycerin induced migraine was model and alcohol exposed neurodegeneration model in Wistar rats to evaluate anti-inflammatory effect of Khurtsiin deed-6 at the 3 different doses of 50, 100and 150 mg/kg, orally. After anesthesia, the brains were removed, then trigeminal nucleus caudal is and hippocampus region isolated from fresh brain. And followed by protein and RNA extraction. Interleukin-1β expression was analyzed by real time polymerase chain reaction. Results: Nitroglycerin induced rat migraine model had increased Interleukin-1β expression in brain TNC area (p&lt;0.001). It has been decreased dramatically after treatment of Khurtsiin deed-6 by doses of 50mg/kg, 100mg/kg and 150mg/kg treatment in brain trigeminal nucleus caudal is region (p&lt;0.01) comparing ibuprofen treated group. Moreover alcohol exposed neurodegeneration rat model had observed increased Interleukin-1β expression in brain Hp area (p&lt;0.001). But Khurtsiin deed-6 doses of 50mg/kg, 100mg/kg and 150mg/kg treatment reduced neuroinflammatory cytokines IL1β expression in hippocampus region (p&lt;0.01, p&lt;0.001) of alcoholic rat models comparing pyridoxamine administrated animals. Conclusion: The present finding indicates that Khurtsiin deed-6shows anti-inflammatory activity decreasing the level of Interleukin -1β cytokine in nitroglycerin induced migraine and alcohol exposed neurodegeneration rat models

Stabilizing Cardiac Ryanodine Receptor With Dantrolene Treatment Prevents Binge Alcohol–Enhanced Atrial Fibrillation in Rats

Binge drinking is a risk factor for cardiac arrhythmias, known as the holiday heart syndrome. Atrial fibrillation (AF) is the most frequently diagnosed arrhythmia in this condition. Recent reports indicated that cardiac ryanodine receptor (RyR2) dysfunction and Ca 2+ leak contribute to alcohol-enhanced AF. In this study, we investigated whether stabilizing RyR2 with dantrolene treatment can prevent alcohol-enhanced AF in rats. A binge drinking rat model was established with alcohol (2 g /kg, IP) delivered once every other day for 4 times. The study consisted of following 3 groups: control group (n = 9), binge alcohol group (n = 10), and binge alcohol + dantrolene (A+D) group (dantrolene, 10 mg/kg, IP before each alcohol injection, n = 9). Echocardiography, left ventricular hemodynamics, in vivo atrial electrophysiology and AF inducibility test, RyR2 phosphorylation level, and blood norepinephrine level were studied 24 hours after the last injection. Ca 2+ leak in isolated atrial myocytes from control and binge alcohol rats was examined. Binge alcohol significantly increased AF inducibility (1/9 in control vs. 8/9 in binge alcohol group, P &lt; 0.05) and AF duration. Dantrolene treatment significantly reduced both AF inducibility (2/9 in dantrolene group, P &lt; 0.05) and AF duration. Binge alcohol significantly increased Ca 2+ leak in isolated atrial myocytes, which was reduced by dantrolene treatment. Blood norepinephrine,7 RyR2 phosphorylation level, cardiac echocardiography, and left ventricular hemodynamics were not significantly affected 24 hours after binge drinking. In conclusion, stabilizing RyR2 with dantrolene treatment significantly attenuated binge drinking-enhanced AF, suggesting that therapeutic strategies stabilizing RyR2 could be a preventive measure to blunt binge drinking-enhanced AF arrhythmogenesis.