Good Therapeutic Agent Research Articles

Evaluation of the antitumor activity of platinum nanoparticles in the treatment of hepatocellular carcinoma induced in rats.

This study aimed to evaluate the antitumor activity of platinum nanoparticles compared with cis-platin both in vitro and in vivo in the treatment of hepatocellular carcinoma induced in rats. The treatment efficacy of platinum nanoparticles was evaluated by measuring antioxidant activities against oxidative stress caused by diethylnitrosamine in liver tissue. The measurements included reduced glutathione content and superoxide dismutase activity, as well as malondialdehyde level. Liver function tests were also determined, in addition to the evaluation of serum alpha-fetoprotein, caspase-3, and cytochrome c in liver tissue. Total RNA extraction from liver tissue samples was also done for the relative quantification of B-cell lymphoma 2, matrix metallopeptidase 9, and tumor protein p53 genes. Histopathological examination was also performed for liver tissue. Results showed that platinum nanoparticles are more potent than cis-platin in treatment of hepatocellular carcinoma induced by diethylnitrosamine in rats as it ameliorated the investigated parameters toward normal control animals. These findings were well appreciated with histopathological studies of diethylnitrosamine group treated with platinum nanoparticles, suggesting that platinum nanoparticles can serve as a good therapeutic agent for the treatment of hepatocellular carcinoma which should attract further studies.

Withania somnifera targets interleukin-8 and cyclooxygenase-2 in human prostate cancer progression.

BackgroundProstate cancer (PC) is a common noncutaneous malignancy in men. The incidence of PC is increasing at an alarming rate across the globe. Progression of PC is associated with elevated levels of interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2) in malignant cells. Overexpression of these players is accompanied by chronic inflammation, increased angiogenesis, proliferation, migration, and inhibition of apoptosis. Moreover, their elevated circulating levels promote the disease progression from androgen-dependent to androgen-independent state. Thus, inhibiting the expression of IL-8 and COX-2 would be a promising target in the development of PC therapeutics. In this study, we investigated the inhibitory effects of Withania somnifera extract on highly metastatic, androgen-independent prostate cancer cell line (PC3). Additionally, we compared the real-time expression of IL-8 and COX-2 in prostate tissue samples.Materials and methodsThe cell viability and cytotoxicity of W. somnifera extract in PC3 cells was quantified colorimetrically by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase leakage assay, respectively. Hematoxylin and eosin staining for histological examination, trypan blue, and acridine orange dyes to enumerate apoptotic and live cells, quantitative real-time polymerase chain reaction to determine the expression and flow cytometry to study the cell cycle analysis were used.ResultsWe observed a significant decrease in the cell viability with a half-maximal inhibitory concentration (IC50) of 10 μg/mL. The expression levels of IL-8 and COX-2 in prostate tissue samples and in PC3 cells were predominantly high; however, the lowest dose of W. somnifera significantly inhibited the enhanced expression of IL-8 and COX-2 in PC3 cells in 24 hours. Furthermore, W. somnifera extract (10 μg/mL) irreversibly arrested the cell cycle in G2/M phase, which was evident from the rapid accumulation of PC3 cells significantly.ConclusionOur results indicate that inherent metastatic and selective inhibitory potential of W. somnifera against PC. W. somnifera may be a good therapeutic agent in addition to the existing drugs for PC. Further studies with more prostate tissue samples are warranted.

In-vitro Evaluation of Thymol Derived from Trachyspermum ammi against Acetaminophen Induced Hepatotoxicity Towards Lymphatic Filariasis Therapeutics

Individuals with lymphatic filariasis (LF) shows elevated levels of pro-inflammatory cytokines, altered expressions of inflammatory genes and are prone to secondary bacterial infection. Also markers of liver dysfunction were reported to be high with increased filarial infection. Acetaminophen (Paracetamol), an anti-pyretic drug was prescribed to LF individuals along with Diethylcarbamazine and Albendazole to alleviate pain and filarial fever within the therapeutic dosage. It is unclear, whether parasite secreted toxins augments the action of acetaminophen and enhances liver dysfunction. Hence, an agent which can attenuate the acetaminophen toxicity during filarial infection is warranted. Trachyspermum ammi (T. ammi) is the richest source of thymol, reported to have anti-filarial lead molecule. In the present study we evaluated the effects of thymol against acetaminophen induced hepatotoxicity in in-vitro settings. In addition, we examined the synergistic effects of thymol against bacterial infection, free radicals and cytokine production. Our results reveal that acetaminophen induces significant reduction in the viability of WRL-68 liver cells compared to cells without treatment. However, thymol at the same concentration restores the cell viability significantly (p=0.031) by attenuating the toxicity within 24h. Thymol inhibits the expression of Interleukin-6 (p=0.043) and Interleukin-8 (p=0.048) in WRL-68 cells and thereby augments maximum protection to liver cells from inflammatory insults. Calorimetric analysis shows the ability of thymol in scavenging hydrazyl (p=0.004) and hydrogen peroxide (p=0.008) free radicals efficiently. Thus thymol derived from T. ammi may be a good therapeutic agent in reducing the toxicity of acetaminophen, may also aids in LF treatment and management in addition to the existing drugs.

Favourable response to rituximab by an ocular adnexal primary lymphoma

Abstract Case report A 70-year-old woman who presented with an extranodal marginal zone B-cell lymphoma in lacrimal gland and conjunctiva. Initial treatment with rituximab yielded an immediate good response. Five months later she showed lymphoid proliferation in her contralateral conjunctiva. Although no additional treatment was performed, the patient has been free of systemic symptoms and recurrences. Discussion Rituximab is a quite good therapeutic agent in low grade adnexal lymphomas.

Protective Effect of Bioactivity Guided Fractions of Ziziphus jujuba Mill. Root Bark against Hepatic Injury and Chronic Inflammation via Inhibiting Inflammatory Markers and Oxidative Stress.

The tribal communities of North Eastern India rely on herbal medicine to cure various disease conditions. Ziziphus jujuba Mill. (Rhamnaceae) is one of such medicinal plants used for curing liver ailments, insomnia, anemia, diarrhea, diabetic complications, cancer, and loss of appetite. The present study was aimed to describe the protective ability of Z. jujuba root bark (ZJRB) against hepatic injury and chronic inflammation. Bioactivity guided fractionation of Z. jujuba methanol extract (ZJME) was performed using different solvents of increasing polarity viz. hexane (ZJHF), chloroform (ZJCF), ethyl acetate (ZJEAF), water (ZJWF), and residue (ZJMR). In vitro antioxidant results revealed that both ZJME and ZJWF possess strong antioxidant activity among all the fractions and mother extract tested. Further, ZJME and ZJWF showed significant protection against CCl4 intoxicated HepG2 cell lines by means of increased cell viability and decreased LDH levels compared to control group. ZJME at 200, 400 mg/kg and ZJWF at 50, 100 mg/kg inhibited the lipid peroxidation and significantly restored the liver function markers (AST, ALT, ALP, LDH, SOD, and CAT) and cytokine levels (TNF-α, Il-1β, and Il-10) in CCl4 induced acute liver damage in rats. All the results were comparable with standard drug silymarin which was further confirmed by histopathology analysis of liver. Similarly, inflammation and increase inflammatory cytokines levels of carrageenan induced paw edema in rats have been refurbished to normal levels on par with the standard drug indomethacin. ZJWF demonstrated potent response than ZJME in all the biological tests conducted. The results of the study signify the ability of ZJRB as good therapeutic agent for liver toxicity and chronic inflammation.

Involvement of heme oxygenase-1 induction in the cytoprotective and neuroinflammatory activities of Siegesbeckia Pubescens isolated from 5,3′-dihydroxy-3,7,4′-trimethoxyflavone in HT22 cells and BV2 cells

Glutamate-induced oxidative injury contributes to neuronal degeneration such as Alzheimer's disease, Parkinson's disease and Huntington's disease in the central nervous system (CNS). Siegesbeckia pubescens is used in oriental medicine to treat arthritis, stroke, rash, edema, and skin itching eczema in South-East Asia. This study provides evidence that 5,3′-dihydroxy-3,7,4′-trimethoxyflavone (DTMF), a compound isolated from 90% MeOH extract of Siegesbeckia pubescens, effectively has neuroprotective and anti-neuroinflammatory activities. DTMF has cytoprotective and reactive oxygen species (ROS) reductive effects in HT22 cells. DTMF also decreased LPS-induced inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2) expression but attenuated LPS-induced nitrite (NO) and prostaglandin E2 (PGE2), as well as TNF-α and IL-1β production. In addition, DTMF induced Heme oxygenase (HO)-1 expression, HO activity, nuclear transcription factor erythroid-2 related factor 2 (Nrf2) nuclear translocation, and antioxidant response element (ARE)-luciferase activity. DTMF increased p38 phosphorylation in HT22 cells and JNK phosphorylation in BV2 microglia cells. Thus, p38 inhibitor (SB203580) in HT22 cells and JNK inhibitor (SP600125) in BV2 microglia cells significantly suppressed HO-1 expression by DTMF. Furthermore, treatment with SnPP (an inhibitor of HO activity) significantly blocked the cytoprotective effects and the anti-neuroinflammatory action of DTMF. In addition, activated microglia-mediated cell death of mouse hippocampal HT22 cells was significantly repressed by DTMF. We also investigated the protective effect of DTMF on the death of glutamate-induced primary mouse hippocampal neurons. These results demonstrated that DTMF may be a good therapeutic agent against neurodegenerative diseases induced by oxidative stress.

RETRACTED: BJ-1103, 6-aminopyridin-3-ol skeletal compound, modulates neuroprotective and anti-neuroinflammatory effects in murine hippocampal and microglial cells via Nrf2-mediated heme oxygenase-1 expression

BJ-1103, as a 6-aminopyridin-3-ol skeletal compound, was originally developed as an antioxidant against free radicals and oxidative stress was prepared from pyridoxine·HCl by the reported procedure. In the present study, we examined the effect of BJ-1103 on neuroprotection and neuroinflammation. Our data showed that BJ-1103 can protect HT22 cells against glutamate-induced cell cytotoxicity. And, BJ-1103 also inhibited LPS-induced inflammatory action. In addition, BJ-1103-induced heme oxygenase-1 (HO-1) expression and elevated HO-1 activities in the two cell lines studied. Additionally, BJ-1103 treatment induced nuclear transcription factor erythroid-2 related factor 2 (Nrf2) and increased the promoter activity of antioxidant response elements (AREs). We have demonstrated using the Nrf2 siRNA, HO inhibitor or HO-1 siRNA that BJ-1103 suppressed neurotoxicity and neuroinflammation through the Nrf2-mediated HO-1 expression. These results demonstrated that BJ-1103 may have good therapeutic agent against neurodegenerative diseases that are induced by oxidative stress and neuroinflammation.

Respuesta favorable a rituximab de un linfoma primario de anejos oculares

Case reportA 70-year-old woman who presented with an extranodal marginal zone B-cell lymphoma in lacrimal gland and conjunctiva. Initial treatment with rituximab yielded an immediate good response. Five months later she showed lymphoid proliferation in her contralateral conjunctiva. Although no additional treatment was performed, the patient has been free of systemic symptoms and recurrences. DiscussionRituximab is a quite good therapeutic agent in low grade adnexal lymphomas.

Anticancer effect of metformin on estrogen receptor-positive and tamoxifen-resistant breast cancer cell lines.

Acquisition of tamoxifen resistance (TR) during anti-estrogenic therapy using tamoxifen is a major obstacle in the treatment of estrogen receptor (ER)-positive breast cancer. As a biguanide derivative, metformin is commonly used to treat type II diabetes. It has recently emerged as a potential anticancer agent. The objective of the present study was to investigate the anticancer activity of metformin in relation to ERα expression and its signaling pathway in ERα-positive MCF-7 and MDA-MB-361 breast cancer cells as well as TR MCF-7 breast cancer cells. Metformin inhibited both protein and mRNA levels of ERα in the presence or absence of estrogen (E2) in the MCF-7, TR MCF-7 and MDA-MB-361 cells. Metformin repressed E2-inducible estrogen response element (ERE) luciferase activity, protein levels and mRNA levels of E2/ERα-regulated genes [including c-Myc, cyclin D1, progesterone receptor (PR) and pS2] to a greater degree than tamoxifen, resulting in inhibition of cell proliferation of MCF-7, TR MCF-7 and MDA-MB-361 cells. Collectively, our results suggest that one of the anticancer mechanisms of metformin could be attributable to the repression of expression and transcriptional activity of ERα. Metformin may be a good therapeutic agent for treating ERα-positive breast cancer by inhibiting the expression and function of ERα. In addition, metformin may be useful to treat tamoxifen-resistant breast cancer.

PAR-1 mediated apoptosis of breast cancer cells by V. cholerae hemagglutinin protease.

Bacterial toxins have emerged as promising agents in cancer treatment strategy. Hemagglutinin (HAP) protease secreted by Vibrio cholerae induced apoptosis in breast cancer cells and regresses tumor growth in mice model. The success of novel cancer therapies depends on their selectivity for cancer cells with limited toxicity for normal tissues. Increased expression of Protease Activated Receptor-1 (PAR-1) has been reported in different malignant cells. In this study we report that HAP induced activation and over expression of PAR-1 in breast cancer cells (EAC). Immunoprecipitation studies have shown that HAP specifically binds with PAR-1. HAP mediated activation of PAR-1 caused nuclear translocation of p50-p65 and the phosphorylation of p38 which triggered the activation of NFκB and MAP kinase signaling pathways. These signaling pathways enhanced the cellular ROS level in malignant cells that induced the intrinsic pathway of cell apoptosis. PAR-1 mediated apoptosis by HAP of malignant breast cells without effecting normal healthy cells in the same environment makes it a good therapeutic agent for treatment of cancer.

A telomerase-derived peptide regulates reactive oxygen species and hepatitis C virus RNA replication in HCV-infected cells via heat shock protein 90

GV1001, a synthetic peptide derived from human telomerase, has a range of diverse biological activities, including an antioxidant function. Here, we investigated the role of GV1001 in hepatitis C virus (HCV)-infected Huh7.5 (JFH-1) cells. We showed that GV1001 inhibited the production of ROS with decreased MAP kinase signaling. Interestingly, GV1001 lost its antioxidant activity as ROS levels decreased, resulting in a reduction in extracellular heat shock protein 90 (eHSP90) as low-density lipoprotein receptor-related protein 1 (LRP1) was blocked or knocked-down. GV1001 binds to eHSP90 and is delivered into the cell by endocytosis via LRP1. Endocytosed GV1001 finally suppressed ROS generation, presumably by hindering the interaction between eHSP90 and NADPH oxidase (NOX). Importantly, GV1001 suppressed HCV RNA replication in JFH-1 cells by inhibiting the binding of HSP90 to FKBP8, a member of the FK506-binding protein family. We also found that HSP90 expression was high in HCV-infected hepatocytes. Therefore, our data suggest that GV1001 may be a good therapeutic agent by controlling HCV RNA replication, as well as by preferentially targeting cells under conditions of oxidative stress.

Preclinical Evaluation of an Epidermal Growth Factor Receptor–Targeted Doxorubicin–Peptide Conjugate: Toxicity, Biodistribution, and Efficacy in Mice

Doxorubicin (DOX) is known to induce apoptosis and necrosis in healthy tissue resulting in unwanted toxicities. To improve the ability of DOX to more specifically target tumors and minimize undesirable side effects, conjugation of DOX with epidermal growth factor receptor (EGFR)–binding peptide (DOX-EBP) has been developed to deliver DOX to EGFR-overexpressing neoplastic cells. Here, we investigated whether DOX-EBP was able to reduce toxicity and enhance anticancer efficacy in vivo through receptor-mediated targeted delivery system. Nude mice were treated with DOX or DOX-EBP to estimate general toxicity, normal tissue damage, biodistribution, and antitumor efficacy. In addition, the expression levels of EGFR in tumor tissues and normal organs were investigated by Western blotting, and their mRNA expression was analyzed by reverse transcription PCR. This study demonstrated that DOX-EBP was able to effectively decrease the distribution of DOX in normal tissues without EGFR overexpressing and reduce DOX-induced toxicity. On the other hand, the research also confirmed that DOX-EBP was able to preferentially accumulate DOX in EGFR-overexpressing tumor tissues and showed the enhanced anticancer efficacy over free DOX. DOX-EBP could be used for receptor-targeted chemotherapy with less toxicity and greater efficacy of tumor cells overexpressing EGFR. DOX-EBP conjugate is a good therapeutic agent for cancer treatment.

Antiviral Activity ofCorylusheterophyllaFisch Against Porcine Epidemic Diarrhea Virus Infection

The porcine epidemic diarrhea virus (PEDV) has recently been shown to cause huge economic losses in the global pork industry. Our results demonstrated that the extract dose-dependently inhibited the replication of PEDV and reduced the visible cytopathic effect (CPE). Treatment with C. heterophylla Fisch extract resulted in marked reduction of PEDV-induced cytokine and chemokine expression. The antiviral activity of C. heterophylla Fisch extract on PEDV replication was found to be primarily exerted at the early stages after infection. Taken together, our data indicate that C. heterophylla Fisch extract may be a good therapeutic agent for use against PEDV and also a potential candidate to be evaluated against other human and animal coronaviruses.

Induction of reactive oxygen species–mediated apoptosis by purified Schisandrae semen essential oil in human leukemia U937 cells through activation of the caspase cascades and nuclear relocation of mitochondrial apoptogenic factors

The aim of this study was to evaluate the beneficial effects of Schisandrae semen essential oil (SSeo) on apoptosis events and the mechanisms associated with these effects in human leukemia U937 cells. The treatment of U937 cells with SSeo significantly inhibited survival and induced apoptosis. Schisandrae semen essential oil treatment increased the levels of death receptors and Fas, and activated caspases accompanied by proteolytic degradation of poly(ADP-ribose)-polymerase, which was associated with the downregulation of members of the inhibitor of apoptosis protein family protein expression; however, a pan-caspase inhibitor reversed SSeo-induced apoptosis. Treating the cells with SSeo also caused truncation of Bid, translocation of proapoptotic Bax to the mitochondria, and loss of mitochondrial membrane permeabilization, thereby inducing the release of cytochrome c into the cytosol. Subsequently, SSeo upregulated the translocation of mitochondrial apoptogenic factors, such as endonuclease G and apoptosis-inducing factor, into the nucleus during the apoptotic process. Notably, SSeo immediately increased the generation of intracellular reactive oxygen species (ROS); however, pretreatment with N-acetylcysteine, a common ROS quencher, almost completely blocked SSeo-induced apoptosis. Taken together, these findings indicate that SSeo caused ROS- and caspase-dependent cell death involving mitochondrial dysfunction and nuclear translocation of mitochondrial proapoptosis proteins. Based on our data, the consumption of Schisandrae semen or its essential oil is a good natural therapeutic agent for anticancer activity and regression.

Honey Dressing vs. Povidone Iodine Dressing.

Dear editor, we would like to discuss on the publication on “Honey Dressing vs. Povidone Iodine Dressing [1].” Gulati et al. concluded that “Honey dressing is highly effective in achieving healing in chronic wounds as compared to Povidone iodine dressing [1].” In fact, the usefulness of honey in wound care is acceptable and honey is widely used. It is approved for the antibacterial activity and proposed to be a good therapeutic agent for infectious diseases [2]. However, the important consideration is the possible contamination of honey. Honey is reported for high contamination by Clostridium pathogen that can cause botulism [3]. To use honey in surgery, good preparation and sanitation control is needed.

Curcumin From Traditional Iranian Medicine to Molecular Medicine

Curcumin might be a good natural therapeutic agent; it could inhibit intercellular inflammation pathways and reduce a lot of unfavorable molecular events in chronic inflammatory diseases.Copyright © 2014, Razavi Hospital; Published by Kowsar Corp. This is an open-access article distributed under the terms of the Creative Commons Attribution Li-cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Ribavirin efficiently suppresses porcine nidovirus replication

Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine epidemic diarrhea virus (PEDV) are porcine nidoviruses that represent emerging viral pathogens causing heavy economic impacts on the swine industry. Although ribavirin is a well-known antiviral drug against a broad range of both DNA and RNA viruses in vitro, its inhibitory effect and mechanism of action on porcine nidovirus replication remains to be elucidated. Therefore, the present study was conducted to determine whether ribavirin suppresses porcine nidovirus infection. Our results demonstrated that ribavirin treatment dose-dependently inhibited the replication of both nidoviruses. The antiviral activity of ribavirin on porcine nidovirus replication was found to be primarily exerted at early times post-infection. Treatment with ribavirin resulted in marked reduction of viral genomic and subgenomic RNA synthesis, viral protein expression, and progeny virus production in a dose-dependent manner. Investigations into the mechanism of action of ribavirin against PRRSV and PEDV revealed that the addition of guanosine to the ribavirin treatment significantly reversed the antiviral effects, suggesting that depletion of the intracellular GTP pool by inhibiting IMP dehydrogenase may be essential for ribavirin activity. Further sequencing analysis showed that the mutation frequency in ribavirin-treated cells was similar to that in untreated cells, indicating that ribavirin did not induce error-prone replication. Taken together, our data indicate that ribavirin might not only be a good therapeutic agent against porcine nidovirus, but also a potential candidate to be evaluated against other human and animal coronaviruses.

A high-dose of fentanyl induced delayed anxiety-like behavior in rats. Prevention by a NMDA receptor antagonist and nitrous oxide (N2O)

Postoperative negative affects such as anxiety need to be better understood and treated to improve patient recovery. The present study evaluates the effect of a single exposure to a high-dose of opioid (4×100μg/kg fentanyl injections in 15min intervals resulting in a total dose of 400μg/kg), as used for surgery in humans, on anxiety-like behavior (ALB) in rats. First, the level of anxiety was evaluated 24-h after a high-dose of fentanyl using an elevated plus-maze apparatus. Second, the preventive effect of BN2572, a N-methyl-d-aspartate receptor (NMDA-R) antagonist, and 50% nitrous oxide (N2O), a gas with NMDA-R antagonist properties, was assessed. A significant increase in ALB was observed in fentanyl‐treated rats. Interestingly, fentanyl-induced ALB was prevented by BN2572, suggesting a NMDA-dependant pathway. Fentanyl-induced ALB was also prevented by a single 50% N2O exposure. The present study provides evidence that deleterious outcomes of opioid use, referred to as “post-opioid syndrome”, include not only pain hypersensitivity as previously described, but also negative affects such as anxiety. Since N2O prevents elements of this post-opioid syndrome, we speculate that N2O could be a good therapeutic agent to facilitate postoperative rehabilitation.

Apigenin induces apoptosis via tumor necrosis factor receptor- and Bcl-2-mediated pathway and enhances susceptibility of head and neck squamous cell carcinoma to 5-fluorouracil and cisplatin

BackgroundApigenin, a natural plant flavone, may have chemopreventive and therapeutic potentials for anti-inflammatory, antioxidant, and anti-cancer. Nevertheless, the anti-tumor effect of apigenin on human head and neck squamous cell carcinoma (HNSCC) is not fully understood. MethodsThe antioxidant capacity and protective effects of apigenin against oxidative stress in murine normal embryonic liver BNLCL2 cells are examined. Cell viability, morphologic change, clonogenic survival, cell cycle distribution, reactive oxygen species (ROS) production, glutathione formation, and death receptors- and Bcl-2-mediated caspase pathways of HNSCC SCC25 cells and A431 cells with apigenin are investigated. ResultsApigenin inhibits the growth of SCC25 and A431 cells and induces cell cycle arrest in the G2/M phase. Apigenin has an antioxidant capacity as well as the ability to inhibit lipid peroxidation. It protects BNLCL2 cells against oxidative damage, and is potentially able to prevent cancer. Apigenin increases intracellular ROS levels and reduces levels of glutathione; it also induces cell apoptosis via tumor necrosis factor receptor (TNF-R)-, TNF-related apoptosis-inducing ligand receptor (TRAIL-R)-, and Bcl-2-mediated caspase-dependent cell death pathways in SCC25 cells. The combination of apigenin with 5-fluorouracil (5-Fu) or cisplatin induces the dramatic death of SCC25 cells. ConclusionsApigenin induces SCC25 cell apoptosis via the up-regulation of both TNF-R and TRAIL-R signaling pathways, and has a synergistic effect on the inhibition of cell proliferation in combination with 5-Fu or cisplatin. General significanceThese analytical findings suggest that apigenin may be a good therapeutic agent against HNSCC cells.

Gastroprotective potential of frutalin, a d-galactose binding lectin, against ethanol-induced gastric lesions

The present study was designed to verify whether frutalin (FTL) affords gastroprotection against the ethanol-induced gastric damage and to examine the underlying mechanism(s). Gastric damage was induced by intragastric administration of 0.2ml of ethanol (96%). Mice in groups were pretreated with FTL (0.25, 0.5 and 1mg/kg; i.p.), cimetidine (100mg/kg; p.o.), or vehicle (0.9% of NaCl, 10mL/kg; p.o.), 30min before ethanol administration. They were sacrificed 30min later, the stomachs excised, and the mucosal lesion area (mm2) measured by planimetry. Gastroprotection was assessed in relation to inhibition of gastric lesion area. To study the gastroprotective mechanism(s), its relations to capsaicin-sensitive fibers, endogenous prostaglandins, nitric oxide, sulphydryls, ATP-sensitive potassium channels, adrenoceptors, opioid receptors and calcium channels were analyzed. Treatments effects on ethanol-associated oxidative stress markers GSH and MDA were measured in gastric tissue. FTL afforded a dose-unrelated gastroprotection against the ethanol damage. However, it failed to prevent the ethanol-induced changes in the levels of GSH and MDA. It was observed that the gastroprotection by FTL was greatly reduced in animals pretreated with capsazepine, indomethacin, L-NAME or glibenclamide. Considering the results, it is suggested that the FTL could probably be a good therapeutic agent for the development of new medicine for the treatment of gastric ulcer.