Acute Toxicity and Gastroprotection Studies with a Newly Synthesized Steroid

Background

Synthetic steroids, such as 9α-bromobeclomethasonedipropionate, have shown gastroprotective activity. For example, the potent glucocorticoid steroid, beclomethasone dipropionate, has been used for treatment of bowel ulcerations. The purpose of the present study was to evaluate the effect of a synthetic steroid, (20S)-22-acetoxymethyl-6β-methoxy-3α,5-dihydro-3′H-cyclopropa[3α,5]-5α-pregnane (AMDCP), on ethanol-induced gastric mucosa injuries in rats.

Methodology/Principal Finding

Rats were divided into 8 groups. The negative control and ethanol control groups were administered Tween 20 (10%v/v) orally. The reference control group, 20 mg/kg omeprazole (10% Tween 20, 5 mL/kg), was administrated orally. The experimental groups received 1, 5, 10, 15 or 20 mg/kg of the AMDCP compound (10% Tween 20, 5 mL/kg). After 60 min, Tween 20 and absolute ethanol was given orally (5 mL/kg) to the negative control group and to the rest of the groups, and the rats were sacrificed an hour later. The acidity of gastric content, gastric wall mucus and areas of mucosal lesions were assessed. In addition, histology and immunohistochemistry of the gastric wall were assessed. Prostaglandin E2 (PGE₂) and malondialdehyde (MDA) content were also measured. The ethanol control group exhibited severe mucosal lesion compared with the experimental groups with fewer mucosal lesions along with a reduction of edema and leukocyte infiltration. Immunohistochemical staining of Hsp70 and Bax proteins showed over-expression and under-expression, respectively, in the experimental groups. The experimental groups also exhibited high levels of PGE₂ as well as a reduced amount of MDA. AMDCP decreased the acidity and lipid peroxidation and increased the levels of antioxidant enzymes.

Conclusion/Significance

The current investigation evaluated the gastroprotective effects of AMDCP on ethanol-induced gastric mucosal lesions in rats. This study also suggests that AMDCP might be useful as a gastroprotective agent.     

Anti-ulcer effect of Ranunculus millefoliatus on absolute alcohol-induced stomach ulceration

Ranunculus millefoliatus (RM) has been reported to have a numeral of biological properties. Though, the influence of this plant extract on stomach ulceration is yet stated. Thirty rats arbitrarily alienated 5 groups: the normal group, the ulcerated control group, the omeprazole group, and 2 investigational groups. Normal and ulcerated control groups were gavage by mouth 10% Tween 20. Omeprazole group fed orally 20 mg/kg omeprazole. Investigational group’s gavage of 250 mg/kg and 500 mg/kg ethanol extracted RM 10% Tween 20, correspondingly. Later another hour, the normal group gavage 10% Tween 20, and groups 2–5 gavage absolute ethanol. Afterward additional hours altogether rats were sacrificed. The ulcerated control group displayed extensive apparent stomach epithelial damage escorted by reduced stomachs mucus excretion and pH stomach contented. RM extract meaningfully condensed ethanol-induced gastric lacerations, for example, demonstrated via augmented gastric mucus and pH stomach contents, condensed ulceration expanse, decreased or lack of edema, and leucocyte penetration hypodermic coat. In stomach epithelial homogenate, RM extract revealed important upsurge superoxide dismutase (SOD), catalase (CAT) actions, expressively diminished malondialdehyde (MDA) level. Furthermore, RM extract augmented strength periodic acid–Schiff (PAS) stain stomach mucosa, besides formed up-regulation heat shock protein 70 (HSP 70) proteins down-regulation the Bcl-2-associated X protein (Bax) protein gastric mucosal. RM extract lessened the level of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and improved the quantity of interleukin-10 (IL-10). Acute toxicity greater dosage of 500 mg/kg RM extract organized not obvious at all toxicology symbols might improve self-protective tools against stomach epithelial abrasions. RM extract presented gastroprotective effects that could be due to capability upsurge pH then mucus discharge, rise SOD and CAT, decrease MDA quantity, up-regulating HSP 70 proteins, down-regulating Bax protein, and moderate provocative cytokines.     

Acute Toxicity and Gastroprotection Studies of a New Schiff Base Derived Copper (II) Complex against Ethanol-Induced Acute Gastric Lesions in Rats

Background

Copper is an essential element in various metabolisms. The investigation was carried out to evaluate acute gastroprotective effects of the Copper (II) complex against ethanol-induced superficial hemorrhagic mucosal lesions in rats.

Methodology/Principal Findings

Rats were divided into 7 groups. Groups 1 and 2 were orally administered with Tween 20 (10% v/v). Group 3 was orally administered with 20 mg/kg omeprazole (10% Tween 20). Groups 4–7 received 10, 20, 40, and 80 mg/kg of the complex (10% Tween 20), respectively. Tween 20 (10% v/v) was given orally to group 1 and absolute ethanol was given orally to groups 2–7, respectively. Rats were sacrificed after 1 h. Group 2 exhibited severe superficial hemorrhagic mucosal lesions. Gastric wall mucus was significantly preserved by the pre-treatment complex. The results showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE₂) activities and a decrease in malondialdehyde (MDA) level. Histology showed marked reduction of hemorrhagic mucosal lesions in groups 4–7. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. PAS staining of groups 4–7 showed intense stain uptake of gastric mucosa. The acute toxicity revealed the non-toxic nature of the compound.

Conclusions/Significance

The gastroprotective effect of the Copper (II) complex may possibly be due to preservation of gastric wall mucus; increase in PGE₂ synthesis; GSH, SOD, and NO up-regulation of Hsp70 protein; decrease in MDA level; and down-regulation of Bax protein.     

Gastroprotective effects of Polygonatum odoratum in rodents by regulation of apoptotic proteins and inflammatory cytokines

In an increasing interest in natural antiulcer compounds that may have gastric healing effects and possibly prevent ulcer recurrence, Polygonatum odoratum appears as a strong candidate. The gastroprotective potentials of P. odoratum rhizome extract (PORE) were explored on ethanol-induced gastric ulceration in rats. Sprague Dawley rats were caged in 5 groups, normal and ulcer control rats received CMC (1% carboxymethyl cellulose). Omeprazole (20 mg/kg) was given to reference Rats. Experimental rats were treated with 250 mg/kg and 500 mg/kg PORE, respectively. After an hour, the normal control rats received 1% CMC, whereas rat groups 2–5 were given absolute ethanol by oral gavage. After 60 min, rats received anesthesia and were sacrificed. Dissected gastric tissue was analyzed by histopathological and immunohistochemical techniques. PORE treatment significantly lowered the ethanol-induced gastric injury, as shown by up-surging gastric pH and mucus content, reduced leukocyte infiltration, lower ulcerative areas in mucosal layers, and increased antioxidants (SOD and CAT) and (MDA) levels. Furthermore, PORE pre-treated rats showed significantly increased expression of the Periodic acid-Schiff (PAS), HSP-70 protein, and decreased Bax protein in their gastric epithelial layers. PORE treatment showed an important regulation of inflammatory cytokines shown by decreasing the TNF-a, and IL-6 and increasing the IL-10 values. The detected biological activity of PORE is encouraging and presents the scientific evidence for its traditional use as a gastroprotection agent however further studies are required to determine the exact phytochemicals and mechanism pathway responsible for this bioactivity.     

Antioxidant and gastroprotective activities of Andrographis paniculata (Hempedu Bumi) in Sprague Dawley rats

Antioxidant and gastroprotective activities of aqueous and ethanolic extract of Andrographis paniculata leaves in rats have been reported. Sprague Dawley rats, 6 per group were used and rats in groups 1 to 6 were pretreated with (0.25% w/v) carboxymethyl cellulose (negative control, 5 ml/kg), 20 mg/kg omeprazole (positive control), (250 mg/kg and 500 mg/kg) of aqueous leaf extracts (APLAE) and (250 and 500 mg/kg) of ethanol leaf extracts (APLEE) respectively. Animals were orally administered with 95% ethanol (5 ml/kg) 60 min after their pretreatments. Rats were sacrificed 1 h after treatment and gastric contents were collected to measure pH and mucous weight. Stomach was analyzed for gross and histological changes. Ulcer control group showed extensive lesions of gastric mucosal layer, whereas rats pretreated with omeprazole, 250 and 500 mg/kg of APLAE showed significant and dose dependent reduction in gastric lesions with increased pH and mucus content of stomach. Rats pretreated with 250 or 500 mg/kg of APLEE showed significantly better inhibition of gastric mucosal lesions. Further, the in vitro antioxidant studies using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay showed that ethanol extracts have superior free radical scavenging activity with IC50 value = 10.9 than aqueous extracts with IC50 value = 24.65. Results of this study showed that pretreatment with ethonolic extract of A. paniculata ethanolic provided significant protection against gastric ulcer by regulating of pH, mucous production and antioxidant property.     

Different diets and amino acid supplementation do not affect the voluntary consumption of ethanol by rats

The effects of four different diets (control diet: 19.5% protein, 60.5% carbohydrate, 10% fat; diet I: 65% protein, 10% carbohydrate, 10% fat; diet II: 5% protein, 76% carbohydrate, 10% fat; diet III: 20% protein, 69% carbohydrate, 1% fat; diet IV: 69% protein, 15% carbohydrate, 1% fat) and supplementation with 3 amino acids (tryptophan: 150 mg/kg/d; arginine: 400 mg/kg/d; taurine: 380 mg/kg/d) on the voluntary consumption of ethanol were investigated in rats using the 2 bottle method. First, rats received the control diet and diets I, II, III and IV for 20 days with a choice of ethanol for the last 6 days only. Ethanol consumption was similar in all dietary groups. Second, rats received the control diet for 8 days followed by diets I, II and IV for another 8 days. Ethanol was offered throughout both periods. The switch to the special diets did not affect ethanol consumption. Third, rats received a control diet with arginine, tryptophan or taurine added to the drinking fluids for 16 days with a choice of ethanol for the last 5 days; thereafter supplementation stopped but the ethanol choice remained. No difference in the voluntary intake of ethanol was noted but ethanol consumption fell after cessation of arginine supplementation. In conclusion, diets differing greatly in their composition or supplementation with these 3 amino acids did not affect the voluntary choice of ethanol by rats in a significant manner.     

Gastroprotective Activity of Ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylidene) Amino]benzoate against Ethanol-Induced Gastric Mucosal Ulcer in Rats

Background

The study was carried out to determine the cytotoxic, antioxidant and gastro-protective effect of ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylid ene)amino] benzoate (ETHAB) in rats.

Methodology/Principal Findings

The cytotoxic effect of ETHAB was assessed using a MTT cleavage assay on a WRL68 cell line, while its antioxidant activity was evaluated in vitro. In the anti-ulcer study, rats were divided into six groups. Group 1 and group 2 received 10% Tween 20 (vehicle). Group 3 received 20 mg/kg Omeprazole. Groups 4, 5 and 6 received ETHAB at doses of 5, 10, and 20 mg/kg, respectively. After an hour, group 1 received the vehicle. Groups 2–6 received absolute ethanol to induce gastric mucosal lesions. In the WRL68 cell line, an IC₅₀ of more than 100 µg/mL was observed. ETHAB results showed antioxidant activity in the DPPH, FRAP, nitric oxide and metal chelating assays. There was no acute toxicity even at the highest dosage (1000 mg/kg). Microscopy showed that rats pretreated with ETHAB revealed protection of gastric mucosa as ascertained by significant increases in superoxide dismutase (SOD), pH level, mucus secretion, reduced gastric lesions, malondialdehyde (MDA) level and remarkable flattened gastric mucosa. Histologically, pretreatment with ETHAB resulted in comparatively better gastric protection, due to reduction of submucosal edema with leucocyte infiltration. PAS staining showed increased intensity in uptake of Alcian blue. In terms of immunohistochemistry, ETHAB showed down-expression of Bax proteins and over-expression of Hsp70 proteins.

Conclusion/Significance

The gastroprotective effect of ETHAB may be attributed to antioxidant activity, increased gastric wall mucus, pH level of gastric contents, SOD activity, decrease in MDA level, ulcer area, flattening of gastric mucosa, reduction of edema and leucocyte infiltration of the submucosal layer, increased PAS staining, up-regulation of Hsp70 protein and suppressed expression of Bax. Key words: ethyl 4-(3, 5-di-ter-butyl-2-hydroxybenzylamino) benzoate; toxicity; antioxidant; gastric-ulcer; anti-ulcer; histology; immunohistochemistry.     

Gastroprotective Effects of Astragaloside IV against Acute Gastric Lesion in Rats

Background

Protection of the gastric mucosa from acute lesions induced by various irritants is a pertinent issue in the field of critical care medicine. In this study, we investigated the gastroprotective effects of astragaloside IV on acute gastric lesions in rats under stressful conditions.

Methods

Rats were randomized into six groups. Group 1 and 2 received 10% Tween 80 (vehicle). Group 3 received 20 mg/kg of omeprazole, a proton pump inhibitor. Groups 4, 5 and 6 received astragaloside IV at concentration of 1, 10, and 50 mg/kg, respectively. As a means to induce gastric lesions, Groups 2–6 were subjected to water immersion and restraint stress for 12 hours after treatment.

Results

Our present studies show that compared to rats in group 2, treatment with 1 to 50 mg/kg astragaloside IV significantly decreased the size of gastric lesions, MDA, TNFα and MCP1 levels, in addition to normalizing gastric pH, gastric mucus and SOD levels (P<0.05). Histomorphological examination confirmed that treatment with astragaloside IV elicited a dosage-dependent protective effect on the gastric mucosa. Furthermore, pretreatment with astragaloside IV resulted in significant elevations in HSP70 and reduction in Bax, along with over-expression of PLCγ response level, which was further confirmed via immunohistochemical analysis.

Conclusions

The acute gastric lesions induced are attenuated by pretreatment with astragaloside IV which is possibly due to the enhancing of the expression of HSP70 with concomitant antioxidant, anti-inflammatory and anti-apoptotic capacity.     

Protective role of ellagitannins from Eucalyptus citriodora against ethanol-induced gastric ulcer in rats: Impact on oxidative stress,inflammation and calcitonin-gene related peptide

The gastroprotective activity of an ellagitannin-rich fraction obtained from Eucalyptus citriodora (ECF) was investigated against ethanol-induced gastric ulceration in rats. The rats were pretreated with ECF (25, 50 and 100 mg/kg) 1 h before the administration of absolute ethanol to induce acute gastric ulceration. The gastric lesions were significantly reduced by all doses of ECF. Notably, pre-treatment with ECF (100 mg/kg) conferred 99.6% gastroprotection, which is significantly higher than that produced by omeprazole. Moreover, ECF administration markedly increased the mucin content in a dose-dependent manner. The potent gastroprotective effect of ECF could be partly mediated by attenuating ethanol-induced oxidative stress. ECF-pre-treatment markedly increased the depleted GSH and SOD levels in a dose-dependent manner. Moreover, ECF significantly decreased the elevated MDA tissue levels induced by ethanol administration. The results demonstrated that ECF administration exerted a powerful anti-inflammatory activity as evidenced by the reduction in the pro-inflammatory markers; IL-1β, TNF-α, 5-LO and COX-2. Additionally, the caspase-3 tissue levels were significantly reduced in the groups pre-treated with ECF. These results suggest that ECF could exert a beneficial gastroprotective effect through their antioxidant, anti-inflammatory and anti-apoptotic properties. Furthermore, ECF pre-treatment significantly attenuated the ethanol-induced decrease in CGRP expression, which has a protective role against gastric ulceration. Histopathological examination revealed intact mucosal layer, absence of hemorrhage and necrosis in groups treated with ECF. Ellagitannins were identified as the major active constituents responsible for the marked antioxidant and gastroprotective properties of ECF. The HPLC–PDA–ESI/MS/MS technique was employed to identify the ellagitannins of E. citriodora.     

Oxidative stress-related lung dysfunction by chromium(VI): alleviation by Citrus aurantium L.

Chromium(VI), a very strong oxidant, causes high cytotoxicity through oxidative stress in tissue systems. Our study investigated the potential ability of ethanolic Citrus aurantium L., family Rutaceae extract, used as a nutritional supplement, to alleviate lung oxidative damage induced by Cr(VI). A high-performance liquid chromatography coupled with a mass spectrometer method was developed to separate and identify flavonoids in C. aurantium L. Six flavonoids were identified, as (1) poncirin, (2) naringin, (3) naringenin, (4) quercetin, (5) isosinensetin, and (6) tetramethyl-o-isoscutellarein. Adult Wistar rats, used in this study, were divided into six groups of six animals each: group I served as controls which received standard diet, group II received via drinking water K₂Cr₂O₇ alone (700 ppm), groups III and IV were pretreated for 10 days with ethanol extract of C. aurantium L. at doses of 100 and 300 mg/kg body weight/day, respectively, and then K₂Cr₂O₇ was administrated during 3 weeks, and groups V and VI received during 10 days only C. aurantium L. ethanol extract at doses of 100 and 300 mg/kg/day, respectively. Ethanol extract of C. aurantium L. was administered orally. Rats exposed to Cr(VI) showed in lung an increase in malondialdehyde and protein carbonyl levels and a decrease in sulflydryl content, glutathione, nonprotein thiol, and vitamins C and E levels. Decreases in enzyme activities such as in Na⁺K⁺ ATPase, catalase, glutathione peroxidase, and superoxide dismutase were noted. Pretreatment with C. aurantium L. of chromium-treated rats ameliorated all biochemical parameters. Lung histological studies confirmed the biochemical parameters and the beneficial role of C. aurantium L.     

Ethanol-Induced Oxidative Stress: The Role of Binaphthyl Diselenide as a Potent Antioxidant

It is widely accepted that oxidative stress plays a central role in alcohol-induced pathogenesis. The protective effect of binaphthyl diselenide (NapSe)2 was investigated in ethanol (Etoh)-induced brain injury. Thirty male adult Wistar rats were divided randomly into five groups of six animals each and treated as follows: (1) The control group received the vehicle (soy bean oil, 1 mL/kg, p.o.). (2) Ethanol group of animals was administered with ethanol (70% v/v, 2 mL/kg, p.o.). (3) (NapSe)2 1 mg/kg, 1 mL/kg plus ethanol 70% (v/v, 2 mL/kg, p.o. (5) (NapSe)2 10 mg/kg, 1 mL/kg) plus ethanol 70% (v/v, 2 mL/kg, p.o). After acute treatment, all rats were sacrificed by decapitation. Evidence for oxidative stress in rat brain was obtained from the observed levels of thiobarbituric acid reactive species, of non-protein thiol (NPSH) groups, and of ascorbic acid, as well as from the activities of catalase (CAT) and of superoxide dismutase (SOD). (NapSe)2 compensated the deficits in the antioxidant defense mechanisms (CAT, SOD, NPSH, and ascorbic acid), and suppressed lipid peroxidation in rat brain resulting from Etoh administration. It was concluded that ethanol exposure causes alterations in the antioxidant defense system and induces oxidative stress in rat brain. (NaPSe)2 at 5 mg/kg restored the antioxidant defenses in rat brain and mitigated the toxic effects of alcohol, suggesting that could be used as a potential therapeutic agent for alcohol-induced oxidative damage in rat brain.     

Effect of artemether on pentobarbitone sleep and electrical activity in rats

Artemether (AM), a highly effective treatment for multidrug-resistant malaria and a component of artemisinin combination therapy, has been associated with some neurotoxicity following repeated high doses. This study was aimed at investigating the effect of AM on pentobarbitone sleep and electrical activities in rats. Wistar rats received AM i.p. at 3 dose levels: 1.5, 7.5, and 15 mg/kg, whereas control rats received 0.2 mL of the vehicle (3% v/v Tween 80). AM administered 20 min before pentobarbitone had no significant effect on the onset and duration of sleep. However, after a 7-day pretreatment, AM dose-dependently prolonged pentobarbitone sleep, as did chloramphenicol. Electroencephalogram and electromyogram recordings 20 min after pretreatment showed that AM (15 mg/kg) exhibited inhibitory activity similar to chlorpromazine as opposed to the excitatory effect of amphetamine. When pretreated for 7 days, rats receiving 1.5 mg/kg AM also showed inhibitory activity of the cortical centres, whereas desynchronization of the optic tectum and reticular formation was observed in rats pretreated with 7.5 and 15 mg/kg AM. The present data suggest that although the therapeutic equivalent dose of 1.5 mg/kg AM had no appreciable effects on pentobarbitone sleep but caused reduced electrical activity in rats, higher doses have more profound effects on both indices.     

The response of circulating parameters of bone mineral metabolism to ethanol- and EDTA-induced hypocalcemia in the rat

The mechanism of the acute hypocalcemia that follows acute ethanol administration has not been established. Measurements of parathyroid hormone (PTH) performed during this hypocalcemia reveal conflicting results. We compared the response of ionized calcium (Ca²⁺), immunoreactive PTH and bone Gla protein (BGP) after ethanol- and EDTA-induced hypocalcemia. 103 male Sprague Dawley rats each weighing approximately 300 g received ethanol and 100 rats of similar weight received EDTA. In each of these studies the animals were divided into experimental and control groups. The ethanol-treated rats received ethanol, 2 g/kg body weight, by ip injection and the EDTA-treated rats received 100 mg EDTA/kg body weight by im injection. Controls received normal saline by the corresponding route of administration. Rats were sacrificed at 0, 30, 60, 90, 180 and 360 min for the measurement of the above parameters. In both experimental groups Ca²⁺ levels were significantly reduced to the same degree by 30 min with return to control values by 360 min. There was no significant difference in immunoreactive PTH, and BGP between control and ethanol-treated groups. In the EDTA-treated rats, however, PTH values were significantly increased at 30 (P < 0.005) and BGP at 60 and 90 minutes (P < 0.005) vs. control. Therefore acute ethanol administration appears to blunt the PTH response to hypocalcemia. A direct inhibitory effect of ethanol on osteoblast function ie BGP production cannot be excluded. In addition, PTH may stimulate BGP.     

The mechanism of cytoprotective effect of CHINOIN-127.

According earlier, investigations nitrogen bridgehead compounds make a representative group of non-prostaglandin type gastroprotective agents. One member of this group is CHINOIN-127 (1,6-dimethyl-4-oxo-1, 6, 7, 8, 9, 9a-hexahydro-4H-pyrido-(1, 2a)-pyrimidine-3-carbox-amide). CHINOIN-127 is a potent non-narcotic analgesic and antiinflammatory agent and has a remarkable protective effect on indomethacin induced ulcer (ED50 = 25 mg/kg p.o.) and on acidified ethanol induced ulcer (ED50 = 26 mg/kg p.o.). In this study we examined the mechanism of action of cytoprotective effect of this drug and we made a comparison between the cytoprotective effect of 20% ethanol and 25 mg/kg CHINOIN-127. In the gastric mucosa of control rats we observed a balance between TxA2 and PGI2 (PGI2/TxA2 = 3.8) and between the cytoprotective prostaglandins (PGI2 and PGE2) and ulcerogen eicosanoids (TxA2 and leukotrienes) (PGI2 + PGE2/TxA2 + LTs = 3.9). 100% ethanol treatment causes disintegration of this balance, shifting the synthesis towards the ulcerogen eicosanoids production. CHINOIN-127 and 20% ethanol pretreatment improves the deranged balance between cytoprotective prostaglandins and ulcerogen eicosanoids. Our results demonstrate that CHINOIN-127 and 20% ethanol have a similar mechanism of cytoprotective action on ethanol induced ulcer in rats.     

Anti-obesity potential of Moringa olifera seed extract and lycopene on high fat diet induced obesity in male Sprauge Dawely rats

Present research explored the anti-obesity effect of Moringa olifera seed oil extract and lycopene (LYC). Forty eight male Sprauge Dawely rats were divided equally into 6 groups. Group Ι (C) served as control, group ΙΙ (MC) was given Moringa olifera seed oil extract (800 mg/kg b.wt) for 8 weeks, group ΙΙΙ (LC) was given (20 mg/kg b.wt) LYC for 8 weeks, group ΙV (O) received high fat diet (HFD) for 20 weeks, group Ѵ (MO), was given HFD for 20 weeks and received (800 mg/kg b.wt) Moringa olifera seed oil extract for last 8 weeks and group ѴΙ (LO), received HFD for 20 weeks and was given (20 mg/kg b.wt) LYC for last 8 weeks. Hematology, lipid peroxidation and antioxidants, non-esterified fatty acids (NEFA), glucose, lipid profile, serum liver and kidney biomarkers, inflammatory markers, leptin, resistin and heart fatty acid binding protein (HFABP) were determined. Also histopathology for liver, kidney and aorta were performed besides immunohistochemistry (IHC) for aortic inducible nitric oxide synthase (iNOS). Administration of Moringa olifera seed oil extract and LYC significantly ameliorated the HFD induced hematological and metabolic perturbations as well as reduced leptin and resistin. Both treatments exerted these effects through promotion of antioxidant enzymes and reducing lipid peroxidation as well as inflammatory cytokines along with reduced iNOS protein expression. Administration of Moringa olifera seed oil extract and LYC have anti-obesity potential in HFD induced obesity in male Sprauge Dawely rats.     

Cardioprotective properties of natural medicine in isoproterenol induced myocardial damage in the male Albino rats

The main aim of this study is to investigate cardioprotective properties of natural medicine inmyocardial damage induced male Albino rats. The aqueous extractof Allium sativumwas used for the determination of phenolic compounds and flavonoids. The amount of phenol (1.39 ± 0.37 GAE/g dry weight) and flavonoids (49.1 ± 2.79 QE/g dry weight) were high in aqueous extract. A. sativumextract and showed 68.39 ± 3.6% DPPHscavenging activity. Isoproterenol was used to induce myocardial injury in Albino rats in vivo by subcutaneous injection (100 mg/kg body weight). To achieve this, experimental animals were categorized into six groups (n = 4), namely, positive, negative control, only isoproterenol administered groups, and garlic extract administered group at 100–300 mg extract/kg body weight. Oxidative stress marker and cardiac markers were assayed to analyze the cardioprotective properties of garlic extract. At 300 mg/kg doseof garlic extract, rat was recovered from various altered factors such as, aspartate aminotransferase, alkaline transminase and alkaline phosphatase. The rats treated with 300 mggarlic extract/kg body weight decreased the level of asparate aminotransferase (126 ± 6.4 IU/L) than other lower doses (100 mg extract/kg and 200 mg extract/kg). Alkaline transaminase level of rat serum level was 81 ± 4.34 IU/L. In the isoproterenol treated rats elevated level was observed (152 ± 4.42 IU/L enzyme activity). Pre-treatment of Albino rat with A. sativum extract reduced cardiac damage. Isoproterenol exposed animal showed 207.6 ± 1.2 mg/dL triglyceride and the garlic administered rat (300 mgextract/kg) reduced LDL-cholesterol level (61.3 ± 1.3 mg/dL) significantly (p < 0.05). Creatinine kinase -MB level was 269.5 ± 12.5 IU/L in the control animal and stress induced animal showed elevated level (572.3 ± 19.4 IU/L). Garlic treated experimental animal (300 µg/kg bw) decreased CK-MB level. To conclude, the aqueous extract of A. sativumshowed cardio protective properties against myocardial injury.     

IGFR-I expression and structural analysis of the hard palatine mucosa in an ethanol-drinking rat strain (UChA and UChB)

The study analyzed the effects of chronic alcohol ingestion on the ultrastructure of the lining epithelium of the hard palatine mucosa of rats UChA and UChB (lines with voluntary alcohol consumption) in order to contribute to the understanding of the consequences of alcohol abuse for the morphology of the digestive system. Thirty female adult animals aged 120 days were divided into three experimental groups. (1) Ten UChA rats (genetically low ethanol consumer) with voluntary intake of 10% v/v (5.45 g/kg/day) ethanol solution and water. (2) Ten UChB (genetically high ethanol consumer) rats with voluntary intake of 10% v/v (7.16 g/kg/day) ethanol solution and water. (3) Ten Wistar rats with voluntary ad libitum water intake (control group). Both groups received Nuvital pellets ad libitum. The IGFR-I expression was intense in both experimental groups. The epithelial cells of the alcoholic rats UChA and UChB showed many alterations such as the presence of lipid droplets, altered nuclei, nuclei in corneum layer and disrupted mitochondria. It was concluded that ethanol intake induces ultrastructural lesions in the hard palatine mucosa.     

Moringa peregrina leaf extracts produce anti-obesity,hypoglycemic, anti-hyperlipidemic,and hepatoprotective effects on high-fat diet fed rats

This present research investigated the anti-obesity and hepatoprotective effects of ethanolic Moringa peregrina leaf (MPLE) and bark extracts (MPBE), in the rats fed with a high-fat diet (HFD). Healthy male rats (n = 48) were randomly distributed to six groups (n = 8): control AIN-93 diet; HFD; HFD + MPBE bark extracts ((300 mg/kg); HFD + MPBE (600 mg/kg); HFD + MPLE (300 mg/kg); HFD + MPLE (600 mg/kg). HFD-fed rats in the Moringa peregrina (MP) treatment groups received orally administered MP leaf or bark extract daily for eight weeks. The results revealed that both doses of MP leaf extract significantly reduced HFD-induced increases in their food intake and the gained body weight, fat pad weights (visceral, subcutaneous, and epididymal), glucose and insulin plasma levels, and leptin and resistin serum levels in HFD-fed rats. Concomitantly, MP leaf extract improved glucose levels after oral or intraperitoneal glucose tolerance tests, reduced serum cholesterol, triglycerides, and the low-density lipoprotein LDL concentration, reduced hepatic triglycerides and cholesterol levels, and increased serum high-density lipoproteins HDL levels and triglycerides and cholesterol levels in fecal. Moreover, the administration of MPLE to HFD-fed rats improved liver architecture, reduced fat accumulation, reduced hepatic malondialdehyde, tumor necrosis factor-α, and interleukin-6 levels. Hepatic glutathione peroxidase, superoxide dismutase, and catalase activities were significantly increased. All observed effects were more pronounced in HFD-fed rats treated with a 600 mg/kg MP dose. However, neither dose of MPBE altered the measured markers in the HFD-fed rats. In conclusion, MPLE showed potential anti-obesity and hepatoprotective activity in HFD-induced obese rats, mediated by reduced lipid absorption, anti-hyperlipidemic effects, and hepatic antioxidant effects.     

Gastroprotective activity of alkaloid extract and 2-phenylquinoline obtained from the bark of Galipea longiflora Krause (Rutaceae)

As part of our continuing search for bioactive natural products from plants, the present study was carried out in order to evaluate the gastroprotective properties of alkaloid extract and 2-phenylquinoline obtained from the bark of Galipea longiflora (Rutaceae). Anti-ulcer assays were performed using the following protocols in mice: nonsteroidal anti-inflammatory drug (NSAID)/bethanecol-induced ulcer, ethanol/HCl-induced ulcer, and stress-induced ulcer. The effects of the extract on gastric content volume, pH and total acidity were also evaluated, using the pylorus ligated model. Treatment using doses of 50, 125 and 250 mg/kg of G. longiflora alkaloid extract and positive controls (omeprazol or cimetidine) significantly diminished the lesion index, total lesion area, and percentage of lesion, in comparison with the negative control groups in all the models evaluated. Regarding the model of gastric secretion, a reduction in volume of gastric juice and total acidity was observed, as well as an increase in gastric pH. The main alkaloid of the plant, 2-phenylquinoline, was also evaluated in the ethanol-induced ulcer model. The results showed that at a dose of 50 mg/kg, it significantly inhibited ulcerative lesions. However, this effect was less than that of the alkaloid extract. All these results taken together show that G. longiflora displays gastroprotective activity, as evidenced by its significant inhibition of the formation of ulcers induced by different models. There are indications that mechanisms involved in anti-ulcer activity are related to a decrease in gastric secretion and an increase in gastric mucus content. Also, there is evidence of involvement of NO in the gastroprotector mechanisms. These effects may be attributed, at least in part, to the presence of some alkaloids, particularly 2-phenylquinoline.     

Influence of small doses of various drug vehicles on acetaminophen-induced liver injury

The biological effects of drug vehicles are often overlooked, often leading to artifacts in acetaminophen-induced liver injury assessment. Therefore, we decided to investigate the effect of dimethylsulfoxide, dimethylformamide, propylene glycol, ethanol, and Tween 20 on acetaminophen-induced liver injury. C57BL/6 male mice received a particular drug vehicle (0.6 or 0.2 mL/kg, i.p.) 30 min before acetaminophen administration (300 mg/kg, i.p.). Control mice received vehicle alone. Liver injury was assessed by measuring the concentration of alanine aminotransferase in plasma and observing histopathological changes. The level of reduced glutathione (GSH) was assessed by measuring total nonprotein hepatic sulfhydrils. Dimethylsulfoxide and dimethylformamide (at both doses) almost completely abolished acetaminophen toxicity. The higher dose of propylene glycol (0.6 mL/kg) was markedly protective, but the lower dose (0.2 mL/kg) was only slightly protective. These solvents also reduced acetaminophen-induced GSH depletion. Dimethylformamide was protective when given 2 h before or 1 h after acetaminophen administration, but was ineffective if given 2.5 h after acetaminophen. Ethanol at the higher dose (0.6 mL/kg) was partially protective, whereas ethanol at the lower dose (0.2 mL/kg) as well as Tween 20 at any dose had no influence. None of the vehicles (0.6 mL/kg) was hepatotoxic per se, and none of them was protective in a model of liver injury caused by D-galactosamine and lipopolysaccharide.