Oral Administration Of Ethanol Research Articles

Effect of ethanolic leaves extract of Myrianthus arboreus on lipid profile of Wistar rats

This study investigated the effect of ethanolic leaves extract of Myrianthus arboreus on lipid profile of Wistar rats. A total of 24 albino Wistar rats divided into 8 groups of three rats each, were orally administered with DMSO as control and varying doses of 1500 mg/KgBw, 1000 mg/KgBw and 500 mg/KgBw for 7days and 14 days respectively. After 7 and 14 days groups 1-4 and 5-8 were sacrificed respectively. Blood samples and hearts of rats were collected for biochemical and histopathology investigations respectively. The result showed non-significant differences (p>0.05) in the mean values of total-cholesterol (T-Chol) and Low density lipoprotein-cholesterol (LDL-Chol.) in all the extract treated groups for 7 and 14 days when compared to mean control values. Mean values of triglyceride (Tg) and very low density lipoprotein-cholesterol (VLDL-Chol) significantly increased (p<0.05) in 1500 and 1000 mg/kgbw extract treated groups for 7days and decreased significantly (p<0.05) in 500 mg/kgbw for 14 days when compared with mean control values. The results also reveal a significant decrease (p<0.05) in the level of high density lipoprotein-cholesterolHDL-Chol) for groups treated 1500 1000 and 500 mg/kgbws for 14 days when compared with control. Phytochemical screening of the plant revealed the presence of alkaloids, flavonoids, glycosides, phenols, saponins and tannins with phenols and tannins having the highest and lowest concentrations of 1185.04 and 16.75 mg/100g respectively. The histopathology results showed normal histology of the heart tissues of animals in groups 1,3-8 while that of group 2 showed inflammation of the heart tissues. In conclusion, oral administration of ethanol leaves extract of Myrianthus arboreus is safe for the heart.

Gastric Mucosal Protective Effects of Cinnamomum cassia in a Rat Model of Ethanol-Induced Gastric Injury.

Cinnamomum cassia (cassia) is a tropical aromatic evergreen tree of the Lauraceae family well known for its fragrance and spicy flavor and widely used in Asian traditional medicine. It has recently garnered attention for its diverse potential health benefits, including anti-inflammatory, anti-cancer, and anti-diabetic properties. However, the gastroprotective effect of C. cassia, particularly against ethanol-induced gastric damage, remains unclear. We investigated the potential gastroprotective property of C. cassia and the underlying mechanisms of action in a rat model of ethanol-induced gastric injury. To assess its effectiveness, rats were fed C. cassia for a 14-day period prior to inducing gastric damage by oral administration of ethanol. Our results indicated that pre-treatment with C. cassia mitigated ethanol-induced gastric mucosal lesions and bleeding. Reduced gastric acid secretion and expression of acid secretion-linked receptors were also observed. Additionally, pretreatment with C. cassia led to decreased levels of inflammatory factors, including TNF-α, p-p65, and IκBα. Notably, C. cassia upregulated the expressions of HO1 and HSP90, with particular emphasis on the enhanced expression of PAS and MUC, the crucial gastric mucosa defense molecules. These findings suggest that C. cassia has protective effects on the gastric mucosa and can effectively reduce oxidative stress and inflammation.

The effect of dry extract of white mistletoe leaves on the change of vasodilation function of the cerebral vascular endothelium in rats with chronic alcohol intoxication

Aim to evaluate the effect of dry extract of mistletoe leafs on the change of vascular endothelium vasodilation function in rats under conditions of chronic alcohol intoxication.
 Material and methods. The chronic alcohol intoxication was modeled in female Wistar rats by course of oral administration of ethanol at the rate of 3g/kg/day. The tested extract and the reference drug ethylmethylhydroxypyridine succinate were administered per os at a dose of 100 mg/kg. The vasodilation function of the vascular endothelium was assessed by the change in the rate of cerebral blood flow during modification of the endogenous nitric oxide synthesis. The concentration of active forms of endothelial and inducible nitric oxide synthase isofrom was determined by enzyme immunoassay.
 Results. The course of the tested extract and the reference drug resulted in an increase in the rate of cerebral blood flow in relation to untreated animals by 48.1% (p0.05) and 40.2% (p0.05), respectively. The restoration of endothelium-dependent vasodilation of cerebral vessels was also noted with the administration of the studied extract of white mistletoe and the reference drug. The analysis of changes in the NO-synthase system showed that, when using the tested extract, the concentration of eNOS increased by 76.3% (p0.05), and iNOS, on the contrary, decreased by 22.1% (p0.05), which was comparable with the indicators of the group of animals receiving the reference drug.
 Conclusion. The use of mistletoe leaf dry extract leads to the restoration of endothelium-dependent vasodilation of cerebral vessels in rats with chronic alcohol intoxication, probably due to the improvement of eNOS-dependent mechanisms of nitric oxide synthesis.

The effects of alpha-pinene on the Nrf2-HO1 signaling pathway in gastric damage in rats.

Alpha-pinene (α-pinene) is a monoterpene with gastroprotective activity. We evaluated the gastroprotective effect of α-pinene in the gastric damage model with ethanol. We evaluated the macroscopic evaluation of the stomach cavity, alteration in pH, mRNA expression of nuclear factor erythroid 2- related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), total antioxidant capacity (TAC) levels, and histopathological changes. Pretreatment with α-pinene (10, 50 and 100 mg/kg i.p.) before oral administration of ethanol reduced gastric mucosal damage by increasing the percentage of ulcer inhibition. Alpha-pinene also increased gastric pH similar to omeprazole. In addition, the histopathological examination showed that in the groups pretreated with α-pinene 50 and 100 mg/kg, and omeprazole20 mg/kg, the lesions were less than the control group. Moreover, α- pinene 10, 50, 100, and omeprazole 20 mg/kg upregulated the NRF2 and HO1. Our results show that pretreatment with α-pinene is effective in reducing ethanol-induced gastric damage through regulation of Nrf2/HO-1.

Boric Acid Alleviates Gastric Ulcer by Regulating Oxidative Stress and Inflammation-Related Multiple Signaling Pathways.

Oxidative stress and inflammation have pivotal roles in gastric ulcer development caused by alcohol consumption. Trace element boric acid taken into the human and animal body from dietary sources displays strong antioxidant and anti-inflammatory functions. However, the mechanisms underlying these actions of boric acid remain unclear, and its effectiveness in preventing gastric lesions is unknown. Therefore, the present study was undertaken to evaluate the protective effects of boric acid in alcohol-induced gastric ulcer and elucidate its potential mechanisms. Gastric ulcer was induced by 75% oral ethanol administration in rats, and the effectiveness of prophylactic boric acid treatment at 100mg/kg concentration was assessed by histopathological examination, ELISA assay and qRT-PCR. Gross macroscopic and histopathological evaluations revealed that boric acid alleviated gastric mucosal lesions. Boric acid decreased reactive oxygen species (ROS) and malondialdehyde (MDA) concentration and the overall oxidation state of the body while improving antioxidant status. It reduced the concentration of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The mRNA expression of JAK2 and STAT3 was decreased while the expression of AMPK was increased with boric acid pretreatment. Moreover, Sema3A and PlexinA1 levels were elevated upon boric acid pretreatment, and homocysteine levels were reduced. Our results demonstrated that boric acid protects gastric mucosa from ethanol-induced damage by regulating oxidative and inflammatory responses. In addition, our findings suggested that the gastroprotective activity of boric acid could be attributed to its regulatory function in the IL-6/JAK2/STAT3 signaling modulated by AMPK and that Sema3A/PlxnA1 axis and homocysteine are potentially involved in this process.

Synergistic Protective Effect of Fermented Schizandrae Fructus Pomace and Hoveniae Semen cum Fructus Extracts Mixture in the Ethanol-Induced Hepatotoxicity.

Schizandrae Fructus (SF), fruits of Schisandra chinensis (Turcz.) Baill. and Hoveniae Semen cum Fructus (HSCF), the dried peduncle of Hovenia dulcis Thunb., have long been used for alcohol detoxification in the traditional medicine of Korea and China. In the current study, we aimed to evaluate the potential synergistic hepatoprotective effect of a combination mixture (MSH) comprising fermented SF pomace (fSFP) and HSCF hot water extracts at a 1:1 (w:w) ratio against ethanol-induced liver toxicity. Subacute ethanol-mediated hepatotoxicity was induced by the oral administration of ethanol (5 g/kg) in C57BL/6J mice once daily for 14 consecutive days. One hour after each ethanol administration, MSH (50, 100, and 200 mg/kg) was also orally administered daily. MSH administration significantly reduced the serum activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase. Histological observation indicated that MSH administration synergistically and significantly decreased the fatty changed region of hepatic parenchyma and the formation of lipid droplet in hepatocytes. Moreover, MSH significantly attenuated the hepatic triglyceride accumulation through reducing lipogenesis genes expression and increasing fatty acid oxidation genes expression. In addition, MSH significantly inhibited protein nitrosylation and lipid peroxidation by lowering cytochrome P450 2E1 enzyme activity and restoring the glutathione level, superoxide dismutase and catalase activity in liver. Furthermore, MSH synergistically decreased the mRNA level of tumor necrosis factor-α in the hepatic tissue. These findings indicate that MSH has potential for preventing alcoholic liver disease through inhibiting hepatic steatosis, oxidative stress, and inflammation.

Protective Effects of the Leaf Aqueous Extract of Manihot Esculenta Crantz Against High-Calorie Diet Combined with Alcohol and Sucrose Ingestion Induced Hypertension in Rats

Manihot esculenta commonly known as cassava is widely distributed across the world. In sub-Saharan Africa, its leaves and tubers are commonly eaten by local populations, who often lend this plant the properties of a traditional medicine. The present study was aimed to evaluate the protective effects of the leaf aqueous extract of Manihot esculenta Crantz against high-calorie diet combined with alcohol and sucrose ingestion induced hypertension in rats. Male wistar rats were randomly divided into three groups of six rats each. Antihypertension activity was evaluated by daily oral administration of Manihot esculenta aqueous extract at the dose of 200 mg/kg bw to rats exposed to high fat/high sucrose diet and daily oral ingestion of sucrose (15%, 5 mL/kg) and ethanol (40°, 5 mL/kg). At the same time, the group 2 or positive control group received high fat/high sucrose diet and daily oral ingestion of sucrose (15%, 5 mL/kg) and ethanol (40°, 5 mL/kg). The last group received standard diet and distilled water (5 mL/kg, orally). During the experimental period (8 weeks), the body weight of animals was daily recorded while the glycaemia was measured every two weeks. The hemodynamic (blood pressure and heart beat) and some serum markers of lipid profile (Triglycerides, total cholesterol, LDL cholesterol and HDL cholesterol), endothelial (NO) and liver functions (AST and ALT) as well as oxidative stress parameters (SOD, CAT, GSH, MDA and TBARS) in the serum and aorta were measured at the end of the study. Our results indicated that Manihot esculenta aqueous extract significantly reduced the body weight gain, diastolic blood pressure, aorta diameter, glycaemia, of animals submitted to both oral administration of sucrose, ethanol and high fat fat/high sucrose diet, and plant extract. Moreover, the administration of Manihot esculenta extract improved the vasodilatation by increasing the endothelial NO secretion. Furthermore, the treatment with this extract improved the balance of the oxidative stress markers and the level of triglyceride, cholesterol and transaminases. Thereby, these results suggest that the leaf aqueous extract of Manihot esculenta could have protective effects against hypertension induced by high-calorie diet combined with alcohol and sucrose ingestion in rats.

Prevotella histicola suppresses ferroptosis to mitigate ethanol-induced gastric mucosal lesions in mice

BackgroundEthanol-induced gastric mucosal lesions (EGML) is one of the most common digestive disorders for which current therapies have limited outcomes in clinical practice. Prevotella histicola (P. histicola) has shown probiotic efficacy against arthritis, multiple sclerosis and oestrogen deficiency-induced depression in mice; however, its role in EGML remains unclear in spite of its extensive colonisation of the stomach. Ferroptosis, which is characterised by lipid peroxidation, may be involved in EGML. Herein, we aimed to investigate the effects and underlying mechanism of action of P. histicola on EGML in the ferroptosis-dependent pathway.MethodsP. histicola was intragastrically administered for a week, and deferoxamine (DFO), a ferroptosis inhibitor, was intraperitoneally injected prior to oral ethanol administration. The gastric mucosal lesions and ferroptosis were assessed via histopathological examinations, quantitative real-time PCR, Western blot, immunohistochemistry and immunofluorescence.ResultsP. histicola was originally found to attenuate EGML by reducing histopathological changes and lipid reactive oxygen species (ROS) accumulation. The pro-ferroptotic genes of Transferrin Receptor (TFR1), Solute Carrier Family 39 Member 14 (SLC39A14), Haem Oxygenase-1 (HMOX-1), Acyl-CoA Synthetase Long-chain Family Member 4 (ACSL4), Cyclooxygenase 2 (COX-2) and mitochondrial Voltage-dependent Anion Channels (VDACs) were up-regulated; the anti-ferroptotic System Xc-/Glutathione Peroxidase 4 (GPX4) axis was inhibited after ethanol administration. However, the changes of histopathology and ferroptosis-related parameters induced by ethanol were reversed by DFO. Furthermore, P. histicola treatment significantly downregulated the expression of ACSL4, HMOX-1 and COX-2, as well as TFR1 and SLC39A14, on mRNA or the protein level, while activating the System Xc-/GPX4 axis.ConclusionsWe found that P. histicola reduces ferroptosis to attenuate EGML by inhibiting the ACSL4- and VDAC-dependent pro-ferroptotic pathways and activating the anti-ferroptotic System Xc-/GPX4 axis.

Population Pharmacokinetics as a Tool to Reevaluate the Complex Disposition of Ethanol in the Fed and Fasted States.

The pharmacokinetics (PK) of ethanolare important in pharmacology and therapeutics because of potential drug-alcohol interactions as well as in forensic science when alcohol-related crimes are investigated.The PK of ethanol have been extensively studied since the 1930s, although some issues remain unresolved, such as the significance of first-pass metabolism, whether zero-order kinetics apply, and the effects of food on bioavailability. We took advantage of nonlinear mixed-effects modeling to describe blood-alcohol concentration (BAC) profiles derived from 3 published clinical studies involving oral, intraduodenal, and intravenous administration of ethanol with and without food. The overall data set included 1510 BACs derived from 72 healthy subjects (60 men, 12 women) aged between 20 and 60 years. Two-compartment models with first-order absorption and Michaelis-Menten elimination kinetics adequately described the BAC profiles. Food intake had 2 separate effects: It reduced the absorption rate constant and accelerated the maximum elimination rate. Estimates of the maximum elimination rate(fasted) and the food effect (as a factor) were 6.31 g/h (95%CI, 6.04-6.59 g/h) and 1.39-fold (95%CI, 1.33-1.46-fold), respectively. Simulations showed thatthe area under the BAC-time curve (AUC) was smaller with lower input rate of ethanol, irrespective of any first-pass metabolism. The AUC from time 0 to 10 hours for a 75-kg subject was 2.34 g• h/L (fed) and 3.83 g• h/L (fasted) after an oral dose of 45 g ethanol. This difference was mainly attributable to the food effect on ethanol elimination and depended less on the absorption rate. Our new approach to explain the complex human PK of ethanol may help when BAC predictions are made in clinical pharmacology and forensic medicine.

Combined carvacrol and cilostazol ameliorate ethanol-induced liver fibrosis in rats: Possible role of SIRT1/Nrf2/HO-1 pathway

Carvacrol is a natural phenolic monoterpenoid, and cilostazol is a selective phosphodiesterase-3 inhibitor with antioxidant, anti-inflammatory and antiapoptotic effects. This experiment aimed to explore the hepatoprotective effects of carvacrol and cilostazol alone and in combination against alcoholic liver fibrosis (ALF), and the underlying mechanisms, using silymarin as a reference anti-fibrotic product.ALF was induced by oral administration of ethanol (1 ml/100 g/day) thrice per week. Silymarin (100 mg/kg), carvacrol (70 mg/kg), cilostazol (50 mg/kg), or carvacrol + cilostazol combination were administered daily and concurrently with ethanol for six weeks. Hepatic changes were evaluated by quantifying serum biomarkers of liver injury, hepatic MDA, GSH and NOx as oxidative stress markers, interleukin (IL)-10 as an anti-inflammatory cytokine, 4-hydroxyproline (4-HYP) as a collagen synthesis indicator, transforming growth factor (TGF)-β1 as a profibrogenic cytokine, α-smooth muscle actin (α-SMA) as a marker of hepatic stellate cells (HSCs) activation, histopathological (necroinflammation and fibrosis) scores and hepatic sirtuin-1 (SIRT1), nuclear factor-erythroid 2-related factor 2 (Nrf2), and hemeoxygenase-1 (HO-1) mRNA levels.Our results showed that carvacrol, cilostazol, and their combination significantly ameliorated ethanol-induced hepatic fibrosis manifested as improving hepatic functions and histopathological features, attenuating α-SMA immunostaining, reducing TGF-β1 and 4-HYP levels, suppressing oxidativeinjury and elevating IL-10 contents. Such effects were accompanied by upregulating SIRT1, Nrf2 and HO-1 genes.This work disclosed for the first time the hepatoprotective effect of carvacrol against ALF and, to a greater extent, with carvacrol + cilostazol combination that could be partially accredited to SIRT1/Nrf2/HO-1 pathway with consequent antioxidant, anti-inflammatory, and anti-fibrotic features.

Mathematical modeling of the kinetics of multiple ethanol intake

The aim of the study is to construct a mathematical model of the kinetics of multiple ethanol intake based on the kinetic equation of zero-order ethanol elimination with absorption and irrevocable first-order absorption deficiency, as well as its implementation in the format of a computer program. Analytical mathematical modeling of the kinetics of multiple oral administration of ethanol is performed on the basis of this kinetic equation. In the course of modeling, a kinetic summation method was developed that allows to perform a mathematical description of the dynamics of ethanol content in the body in the case of repeated intake of alcoholic beverages of any volume and strength, separated by time intervals of any duration. The developed computational algorithm is implemented in the format of the Alcohol Calculator V 3.0 computer program. The conclusion is made about the expediency of using the developed information and computing technology in the forensic assessment of the quantitative alcohol content in the body at a legally relevant time.

Chemosensory representation of first-time oral exposure to ethanol in the orbitofrontal cortex of mice.

Intermittent ethanol consumption changes the neuronal activity of the orbitofrontal cortex (OFC) in rodents, which has been attributed to important participation in the development of addiction, particularly alcoholism. The OFC participates in gustatory sensory integration. However, it is unknown whether this region can encode chemosensory elements of oral ethanol administration independently of the consumption movement (orofacial motor response) when administered for the first time (naïve mice). To answer this question, we used a sedated mouse model and a temporary analysis protocol to register extracellular neuronal responses during the oral administration of ethanol. Our results show an increase in neuronal frequency (in the first 500ms) when low (0.6, 1, and 2.1M) and high (3.2, 4.3, and 8.6M) concentrations of ethanol are orally administered. The modulatory effect of ethanol was observed from low and high concentrations and differed from the tastants. There was consistent neuronal activity independent of the concentration of ethanol. Our results demonstrate a sensory representation of oral ethanol stimulation in the OFC neurons of naïve mice under sedation.

Orally administered zingerone does not mitigate alcohol-induced hepatic oxidative stress in growing Sprague Dawley rat pups

Neonatal alcohol exposure (NAE) can induce oxidative stress. We determined whether zingerone (ZO), a phytochemical with anti-oxidant activity, can mitigate the negative impact of neonatal alcohol-induced oxidative stress. Seventy ten-day-old Sprague-Dawley rat pups (35 male, 35 female) were randomly assigned and administered the following treatment regimens daily from postnatal day (PND) 12–21: group 1 – nutritive milk (NM), group 2 – NM +1 g/kg ethanol (Eth), group 3 – NM + 40 mg/kg ZO, group 4 – NM + Eth + ZO. Growth performance, blood glucose and plasma triglycerides (TGs), total cholesterol, HDL-cholesterol, leptin and insulin concentration were determined. Cytochrome p450E21(CYP2E1) and thiobarbituric acid (TBARS); markers of hepatic oxidative stress and catalase, superoxide dismutase (SOD) and total glutathione (GSH), anti-oxidant markers of the pups were determined. Oral administration of ethanol (NM + Eth), zingerone (NM + ZO) and combined ethanol and zingerone (NM + Eth + ZO) did not affect the growth performance and insulin and leptin concentration of the rats (p > 0.05). Ethanol significantly reduced plasma TGs concentration of female rats (p = 0.04 vs control). However, ethanol and/or its combination with zingerone decreased hepatic GSH (p = 0.02 vs control) and increased CYP2E1 (p = 0.0002 vs control) activity in male rat pups. Zingerone had no effect (p > 0.05 vs control) on the rats' CYP2E1, GSH, SOD and catalase activities. Neonatal alcohol administration elicited hepatic oxidative stress in male rat pups only, showing sexual dimorphism. Zingerone (NM + ZO) prevented an increase in CYP2E1 activity and a decrease in GSH concentration but did not prevent the alcohol-induced hepatic oxidative stress in the male rat pups.

Effect of concomitant oral administration of ethanol on the pharmacokinetics of nicardipine in rats.

Ethanol intake can alter pharmacokinetics by increasing the solubility or enhancing the absorption of concomitant drugs. Here, a selective, sensitive and reproducible high-performance liquid chromatography-tandem mass spectrometry method for the quantitative analysis of nicardipine in rat plasma was developed using simple protein precipitation. The calibration curve was linear over a concentration range of 1-2,000 ng/ml (r2 > 0.998). Accuracy ranged from 93.4 to 112.2% and precision was within 12.1% from three independent analytical batches. Stable conditions for the quantification of nicardipine in rat plasma were established in various conditions, including sample storage and handling. The matrix effect was negligible, and recovery was consistent at three different levels of quality control sample. The method was applied to assessment for the effect of ethanol on the pharmacokinetics of nicardipine in rats. The oral bioavailability of nicardipine was increased from 5.4 to 9.4% in Sprague-Dawley rats by concomitant oral administration of ethanol whereas the half-life was not altered. The findings indicated that concomitant ethanol intake can increase systemic drug exposure by increasing gastrointestinal absorption, especially poorly soluble drugs. This study provides an insight for further investigation of the alteration of the pharmacological effect of poorly soluble drugs owing to ethanol intake.

D-ribose-L-cysteine exhibits neuroprotective activity through inhibition of oxido-behavioral dysfunctions and modulated activities of neurotransmitters in the cerebellum of Juvenile mice exposed to ethanol

Alcohol exposure to the cerebellum has been known to trigger cerebellar dysfunctions through several mechanisms. This present study was designed to evaluate the repealing effect of D-ribose-L-cysteine (DRLC) on alcohol-induced cerebellar dysfunctions in juvenile BALB/c mice. The animals were randomly divided into 4 groups (n = 10 per group). Mice were given oral administration of normal saline (control), DRLC (100 mg/kg, p.o), ethanol (0.2 mL of 10% w/v), or DRLC (100 mg/kg, p.o) + ethanol (0.2 mL of 10% w/v). On day 29 of the study (i.e., 24 h after the administration of the last respective doses), neurochemical quantification of the respective levels of serotonin and dopamine, lipid peroxidation, total antioxidant, superoxide dismutase, and glutathione peroxidase in the cerebellar tissues of the mice were analyzed. Compared with the saline-treated group, the studied neurochemical indices were modulated across the various experimental groups. The administration of ethanol significantly modulates the levels of monoamine neurotransmitters (serotonin and dopamine) as well as contents of total antioxidants, activities of superoxide dismutase, and glutathione peroxidase, with a concurrently increased level of lipid peroxidase in the cerebellar tissue of the mice. DRLC significantly reverses these effects in the DRLC + ethanol co-treated group. Combined exposure to DRLC + ethanol counteracts the deleterious effect of ethanol in the cerebellum of juvenile BALB/c mice via monoamine neurotransmitter, lipid peroxidation, total antioxidant status, superoxide dismutase, and glutathione peroxidase action pathways. Therefore, DRLC could be a pharmacologic or therapeutic agent in attenuating the deleterious effects of alcohol on the cerebellum.

Cytoprotective Effect of Methanol Extract of Laportea aestuans on Acidified Ethanol-induced Gastric Ulcer in Male Wistar Rats

Laportea aestuans (Urticaceae) plant is widely distributed in tropical rain forests and used as remedial agent for various diseases in Nigeria by herbal practitioners. Ethanol consumption is one of the common causes of gastric ulcer due to excessive generation of reactive oxygen species and erosion of gastric mucosal layer. This study investigated the cytoprotective effect of pretreatment with methanol extract of Laportea aestuans (MELA) for 7 days on ethanol-induced gastric ulcer in male Wistar rats using cimetidine as a standard drug. Ulcerogenic parameters, oxidative damage, inflammatory and apoptotic markers were evaluated. MELA showed a significant dose-dependent (p < 0.01) decrease in ulcer score (US), ulcer index (UI) and peptic activity with an increase in mucus content and percentage inhibition compared to the ethanol group. Activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), Glutathione S-transferase (GST) and level of reduced glutathione (GSH) were also increased with concomitant decrease in malondialdehyde (MDA) level in MELA treated rats. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and activities of cytochrome c (Cyt c), caspases-3 and -9 (CASPS-3 and -9) were also reduced by administration of MELA. Taking together, this study shows that MELA protected the gastric mucosal against the assault induced by ethanol via upregulation of the antioxidant system, and downregulation of inflammatory and apoptotic processes.
 HIGHLIGHTS
 
 Oral administration of ethanol to Wistar rats induced gastric ulceration
 Oral administration of ethanol to Wistar rats caused ulcer by generation of ROS, inflammation and induce apoptosis
 Pretreatment of rats with methanol extract of Laportea aestuans (MELA) preserved the gastric mucosal integrityby boosting antioxidant defence system and inhibiting inflammatory and apoptotic processes
 
 GRAPHICAL ABSTRACT

Antioxidant Properties, Phytoactive Compounds and Potential Protective Action of Salvia officinalis Flowers Against Combined Gastro-Intestinal Ulcer and Diarrhea Experimentally Induced in Rat.

The present study was conducted to investigate the protective action of Salvia officinalis flowers aqueous extract (SOFAE) against combined gastro-intestinal (GI) disorders-induced by ethanol and castor oil administration in rats. Adult male Wistar rats were divided into seven groups of ten each and various doses of SOFAE (50, 100, and 200 mg kg−1, b.w., p.o.) and sulfasalazine (100 mg kg−1, b.w., p.o.) were daily administrated during 15 days. After, animals were intoxicated with a single oral administration of ethanol (4 g kg−1, b.w., p.o.) and castor oil (5 mL kg−1, b.w., p.o.). We found that SOFAE contains several phytoactive compounds with a strong ABTS scavenging ability. In vivo, we showed that SOFAE protected against EtOH/CO-induced macroscopic and histological alterations in GI tract accompanied by intestinal fluid accumulation and gastric juice decrease. SOFAE significantly counteracted lipoperoxydation increase and reversed the depletion of both enzymatic and non-enzymatic antioxidants. More importantly, SOFAE significantly reduced the levels of inflammatory markers (CRP and ALP) in plasma and mucosal GI tract. In conclusion, our data clearly indicate that the SOFAE exerted a potential protective effect against EtOH-induced peptic ulcer combined with CO-induced diarrhea in rats. These effects could be associated with its antioxidant and anti-inflammatory properties.

ANTI-ULCER ACTIVITY OF HYDRO-ALCOHOLIC EXTRACT OF SARACA ASOCA STEM BARK IN RATS

In the present study effort has been made to establish the antiulcer activity of Saraca asoca (Roxb.), De Wild (family-Caesalpinaceae) stem bark hydroalcoholic-extract using ethanol induced ulceration model in albino rats, because no systematic study has been reported for its antiulcer activity. The effect of hydro-alcoholic extract (60:40) of S. asoca bark was investigated by carrying out an acute toxicity study in albino rats to evaluate the antiulcerogenic activity by using ethanol induced gastric ulcer model compared with omeprazole as standard drug. The preliminary photochemical screening of this medicinal plant identified the presence of important secondary metabolites like flavonoids and tannins. Acute toxicity study did not manifest any toxicological signs in rats. Oral administration of absolute ethanol (99.5 %, 5 mL kg -1, p.o.) produced significant ulcers index (41.00 ± 1.75) in the control group. Standard drug omeprazole (40 mL kg -1, p.o.) produced ulcer index (12.17 ± 0.74). Ulcer index (24.17 ± 1.40) is significantly (p<0.001) protected by hydro-alcoholic extract of S. asoca (stem bark) at a dose of 200 mL kg -1, p.o. The present finding suggests that hydro-alcoholic extract of S. asoca (stem bark) promotes ulcer protection activity.

Anti-Ulcer Activities of Methanolic Extract of Musa Paradisiaca

Musa paradisiaca (plantain peel) is useful in prevention and control of numerous health problems in Ayurveda, an ancient system of medicine. The anti-ulcer activity and effects of varied dosages of its methanolic extract on gastrointestinal motility were investigated in this study. Fifteen (15) Wistar rats of 150 and 200 g were deprived of food for 24 hours; then divided into five groups (Groups I through V) of three rats each; while group I (control) received 5ml/kg of distilled water, groups II, III and IV received 100 mg/kg of indomethacin (ulceric), 5mg/kg of omeprazole (after inducing ulcer), and 200 mg/kg of M. paradisiaca respectively. After inducing ulcers with indomethacin, Group V animals were fed (orally) with 400mg/kg of extract. Oral administration of ethanol injured the mucosal lining, resulting in gastrointestinal bleeding with ulcer indexes of 13.30, 10.57, 10.62, and 9.01 in groups II to V respectively, after some time of administration of test substances. In addition, the test statistic (using ANOVA and Tukey post-hoc) on the Omeprazole and 400mg/kg extract treated groups showed a substantial protection of 8.60% and 21.27 % respectively; whereas, the Omeprazole and 400mg/kg extract treated groups had a substantial protection of 8.60% and 21.27%, respectively. Between the omeprazole, 200mg/kg and 400mg/kg of extract treated groups, there was a statistically insignificant increase (p 0.05) in gastro-protective activity. However, gastro-protective effect was statistically significant (p 0.05) at larger doses of the extract. The ulcer index decreased significantly (p 0.05) between the negative control and treatment groups, according to the findings. However, with 400mg/kg body weight of the extract, the percentage gastro-protective action was higher than in the omeprazole-treated group. We advocate using a similar extract on other platforms to back up this study's efforts.

Alteration of oxidative-stress and related marker levels in mouse colonic tissues and fecal microbiota structures with chronic ethanol administration: Implications for the pathogenesis of ethanol-related colorectal cancer.

Chronic ethanol consumption is a risk factor for colorectal cancer, and ethanol-induced reactive oxygen species have been suggested to play important roles in the pathogenesis of ethanol-related colorectal cancer (ER-CRC). In this study, the effects of 10-week chronic administration of ethanol on the colonic levels of oxidative stress and advance glycation end product (AGE) levels, as well as fecal microbiota structures, were examined in a mouse model. Chronic oral administration of ethanol in mice (1.0 mL of 1.5% or 5.0% ethanol (v/v) per day per mouse, up to 10 weeks) resulted in the elevation of colonic levels of oxidative stress markers (such as 8-hydroxy-2’-deoxyguanosine and 4-hydroxynonenal) compared to control mice, and this was consistently accompanied by elevated levels of inflammation-associated cytokines and immune cells (Th17 and macrophages) and a decreased level of regulatory T (Treg) cells to produce colonic lesions. It also resulted in an alteration of mouse fecal microbiota structures, reminiscent of the alterations observed in human inflammatory bowel disease, and this appeared to be consistent with the proposed sustained generation of oxidative stress in the colonic environment during chronic ethanol consumption. Moreover, the first experimental evidence that chronic ethanol administration results in elevated levels of advanced glycation end products (AGEs) and their receptors (RAGE) in the colonic tissues in mice is also shown, implying enhanced RAGE-mediated signaling with chronic ethanol administration. The RAGE-mediated signaling pathway has thus far been implicated as a link between the accumulation of AGEs and the development of many types of chronic colitis and cancers. Thus, enhancement of this pathway likely exacerbates the ethanol-induced inflammatory states of colonic tissues and might at least partly contribute to the pathogenesis of ER-CRC.