{"title":"Evaluation of the Efficacy of Tofacitinib, a JAK Inhibitor, in Alleviating Sepsis-Induced Multiple Organ Dysfunction Syndrome.","authors":"Vaishnavi Singh, Kavita Joshi, Samit Chatterjee, Sameer Qureshi, Snigdha Siddh, Vandana Nunia","doi":"10.1055/a-2372-3446","DOIUrl":"10.1055/a-2372-3446","url":null,"abstract":"<p><p>Sepsis, a life-threatening condition triggered by an uncontrolled response to infection, results in a systemic inflammatory response syndrome (SIRS) and the failure of multiple organs leading to multiple organ dysfunction (MODS). In the present study, we investigated the therapeutic potential of tofacitinib (TOFA), an FDA-approved inhibitor of JAK1 and JAK3 against sepsis, using a mouse model induced by cecal ligation puncture (CLP). Swiss albino mice were employed to replicate the CLP-induced sepsis model and were randomly divided into four groups: control, CLP, 150 mg/kg TOFA, and 300 mg/kg TOFA. Six hours after the last TOFA dose, we collected blood and tissue samples from the liver, lungs, kidneys, and spleen for histological analysis. Blood samples were used to assess granulocyte and lymphocyte percentages. Throughout the experiment, we monitored body weight and short-term survival. Our comparative histological analysis revealed that 150 mg/kg TOFA had a protective effect against multiple organ damage. Conversely, the study highlighted the harmful effects of 300 mg/kg TOFA, primarily due to liver and renal toxicity within this group. In summary, our findings demonstrate that tofacitinib at an optimal dose of 150 mg/kg showed promise as a potential therapeutic intervention for sepsis-induced multiple organ failure. However, caution is warranted when considering higher dosages.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"394-404"},"PeriodicalIF":1.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug ResearchPub Date : 2024-10-01DOI: 10.1055/a-2401-4578
Manoj Bisht, Jai Parkash Kadian, Tanuj Hooda, Neelam Jain, Amit Lather, Navidha Aggarwal
{"title":"Explore the Role of the Sphingosine-1-Phosphate Signalling as a Novel Promising Therapeutic Target for the Management of Parkinson's Disease.","authors":"Manoj Bisht, Jai Parkash Kadian, Tanuj Hooda, Neelam Jain, Amit Lather, Navidha Aggarwal","doi":"10.1055/a-2401-4578","DOIUrl":"10.1055/a-2401-4578","url":null,"abstract":"<p><p>Sphingosine-1-phosphate (S1P) is a cellular signalling molecule derived from sphingosine, which is a pro-apoptotic sphingolipid. Sphingolipids control various cellular actions like growth, homeostasis, and stress-related responses. The main sources of S1P in our body are erythrocytes. S1P controls both cellular mediators and other second messengers intracellularly. The S1P receptor also helps in inflammatory and neuroprotective effects (required to manage of Parkinson's). A large number of anti-Parkinson drugs are available, but still, there is a need for more effective and safer drugs. S1P and its receptors could be targeted as novel drugs due to their involvement in neuro-inflammation and Parkinson's. The present review effort to explore the biological role of S1P and related receptors, for their possible involvement in PD; furthermore. Overall, S1P and other related metabolizing enzymes have significant therapeutic opportunities for Parkinson's disease along with other neurological disorders.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":"74 8","pages":"365-378"},"PeriodicalIF":1.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug ResearchPub Date : 2024-10-01Epub Date: 2024-08-22DOI: 10.1055/a-2381-6882
Kian Mousavi-Nasab, Mohammad Amani, Sara Mostafalou
{"title":"The Effect of Trientine on AlCl3-Induced Cognitive Dysfunction and Biochemical Changes in the Hippocampus of Rats.","authors":"Kian Mousavi-Nasab, Mohammad Amani, Sara Mostafalou","doi":"10.1055/a-2381-6882","DOIUrl":"10.1055/a-2381-6882","url":null,"abstract":"<p><p>Cognitive impairments affect millions of people worldwide with an increasing prevalence. Research on their etiology and treatment is developing, nevertheless significant gaps remain. Trientine (TETA), as a copper chelator, has been shown to have beneficial effects in different human chronic diseases such as diabetic cardiomyopathy and neuropathy. Here, we examined the impact of TETA on AlCl3-induced neurocognitive dysfunctions and molecular changes in the hippocampus of rats.Thirty-six male Wistar rats (weighing 200-250 g) were randomly divided into four groups including control, TETA (100 mg/kg/day), AlCl3 (100 mg/kg/day), and AlCl3 (100 mg/kg/day)+TETA (100 mg/kg/day), and received chemicals by gavage for 30 days. At the end of the treatment, the open field maze, elevated plus maze, novel object recognition memory test, and shuttle box test were done. Then after, brain-derived neurotrophic factor (BDNF), glycogen synthase kinase-3 β (GSK-3β), acetylcholinesterase activity, oxidative stress markers, and inflammatory mediators were measured in the hippocampus.AlCl3 increased anxiety-like behaviors and impaired recognition and short-term memory. TETA was able to improve AlCl3-induced anxiety-like behaviors and short-term memory dysfunction. In the AlCl3-treated group, there was a significant increase in GSK-3β, oxidative stress, pro-inflammatory and pro-apoptotic markers, and decreased BDNF in the hippocampus. Co-administration of TETA was able to decrease lipid peroxidation, inflammation, GSK-3β, and acetylcholinesterase activity, and increase BDNF in the hippocampus compared with AlCl3-treated rats.It can be concluded that TETA was able to improve neurobehavioral and neurocognitive functions by alleviating oxidative stress, inflammation, and pro-apoptotic pathways leading to the normalization of BDNF and GSK-3β.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"405-414"},"PeriodicalIF":1.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interaction of Purine and its Derivatives with A1, A2-Adenosine Receptors and Vascular Endothelial Growth Factor Receptor-1 (Vegf-R1) as a Therapeutic Alternative to Treat Cancer.","authors":"Lauro Figueroa, Marcela Rosas, Magdalena Alvarez, Emilio Aguilar, Virginia Mateu, Enrique Bonilla","doi":"10.1055/a-2376-5771","DOIUrl":"10.1055/a-2376-5771","url":null,"abstract":"<p><strong>Background: </strong>There are several studies that indicate that cancer development may be conditioned by the activation of some biological systems that involve the interaction of different biomolecules, such as adenosine and vascular endothelial growth factor. These biomolecules have been targeted of some drugs for treat of cancer; however, there is little information on the interaction of purine derivatives with adenosine and vascular endothelial growth factor receptor (VEGF-R1).</p><p><strong>Objective: </strong>The aim of this research was to determine the possible interaction of purine (1: ) and their derivatives (2-31: ) with A<sub>1</sub>, A<sub>2</sub>-adenosine receptors, and VEGF-R1.</p><p><strong>Methods: </strong>Theoretical interaction of purine and their derivatives with A<sub>1</sub>, A<sub>2</sub>-adenosine receptors and VEGF-R1 was carried out using the 5uen, 5mzj and 3hng proteins as theoretical tools. Besides, adenosine, cgs-15943, rolofylline, cvt-124, wrc-0571, luf-5834, cvt-6883, AZD-4635, cabozantinib, pazopanib, regorafenib, and sorafenib drugs were used as controls.</p><p><strong>Results: </strong>The results showed differences in the number of aminoacid residues involved in the interaction of purine and their derivatives with 5uen, 5mzj and 3hng proteins compared with the controls. Besides, the inhibition constants (Ki) values for purine and their derivatives 5: , 9: , 10: , 14: , 15: , 16: , and 20: were lower compared with the controls CONCLUSIONS: Theoretical data suggest that purine and their derivatives 5: , 9: , 10: , 14: , 15: , 16: , and 20: could produce changes in cancer cell growth through inhibition of A<sub>1</sub>, A<sub>2</sub>-adenosine receptors and VEGFR-1 inhibition. These data indicate that these purine derivatives could be a therapeutic alternative to treat some types of cancer.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"379-393"},"PeriodicalIF":1.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessing the Compatibility of Menatetrenone with Excipients: A Spectroscopic Approach and Implication in Drug Formulation Development.","authors":"Widhilika Singh, Poonam Kushwaha, Shom Prakash Kushwaha","doi":"10.1055/a-2361-2895","DOIUrl":"10.1055/a-2361-2895","url":null,"abstract":"<p><p>An experiment was conducted to evaluate the compatibility of menatetrenone with selected pharmaceutical excipients. Fourier Transform Infrared Spectroscopy (FTIR) was used to assess drug-excipient compatibility. The present research systematically investigates the FTIR spectrum of each chemical compound separately and their physical blends, analyzing for possible shifts, alterations or novel peak that may indicate chemical interactions. This study aims to utilize spectral data interpretation to detect potential compatibility problems that may occur while design and production of menatetrenone containing dosage forms ensuring their increased stability and effectiveness. The FTIR results demonstrated that all the pharmaceutical excipients were compatible with menatetrenone. In conclusion, the compatibility of pharmaceutical excipients with menatetrenone was successfully assessed using FTIR that will aid in future design of formulations containing menatetrenone as therapeutic moiety.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"347-359"},"PeriodicalIF":1.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug ResearchPub Date : 2024-09-01Epub Date: 2024-07-19DOI: 10.1055/a-2357-8095
Nasir Idkaidek, Aya Al-Tarawneh, Laith Alshoaibi, Haya Tuffaha, Asma Zinati, Majed Abdelqader, Ahmad Al-Ghazawi, Ayman Rabayah, Salim Hamadi
{"title":"Saliva Versus Plasma Therapeutic Drug Monitoring of Valproic Acid in Jordanian Patients.","authors":"Nasir Idkaidek, Aya Al-Tarawneh, Laith Alshoaibi, Haya Tuffaha, Asma Zinati, Majed Abdelqader, Ahmad Al-Ghazawi, Ayman Rabayah, Salim Hamadi","doi":"10.1055/a-2357-8095","DOIUrl":"10.1055/a-2357-8095","url":null,"abstract":"<p><p>Therapeutic drug monitoring is used to ensure that medications are prescribed and administered according to safe doseage advice and for the purpose of achieving the desired therapeutic effects in patients. Several methods are used to perform therapeutic drug monitoring. However, there is insufficient evidence to currently support therapeutic drug monitoring of Valproic acid using salivary samples. The aim of this paper is to determine the feasibility of using salivary samples as a substitute for plasma samples for therapeutic drug monitoring of Valproic acid. In this study a total of 23 patients participated, with the mean age of 33.39. Salivary and plasma samples were collected and analysed to determine the peak and trough concentrations of Valproic acid for comparison between the two methods. Calibrated LC- MS/ MS was used to measure Valproic acid levels. Statistical analyses were performed using ANOVA test and ethical approval was obtained prior to sample collection. The results showed that saliva Valproic acid levels were less than that of plasma levels. There was no significant correlation between saliva and plasma level of Valproic acid (P>0.05). However, there was a significant correlation between the area under the curve for both saliva and plasma Valproic acid (P<0.05). Creatinine clearance was significantly correlated with peak plasma levels of Valproic acid (P<0.05). Albumin was significantly correlated with plasma levels of Valproic acid. There was also a significantly positive and moderate relationship between Log Saliva Cmax and Log plasma free Valproic acid concentration (r=0.76, p<0.018). In conclusion, saliva samples can be used as a substitute for plasma samples in the therapeutic drug monitoring of Valproic acid.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"314-324"},"PeriodicalIF":1.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug ResearchPub Date : 2024-09-01Epub Date: 2024-07-11DOI: 10.1055/a-2347-9824
Mawrah Arshad, Farazul Hoda, Nasir Ali Siddiqui, Abul Kalam Najmi, Mohammad Ahmad
{"title":"Genito Urinary Infection and Urinary Tract Infection in Patients with Type 2 Diabetes Mellitus Receiving SGLT2 Inhibitors: Evidence from a Systematic Literature Review of Landmark Randomized Clinical Trial.","authors":"Mawrah Arshad, Farazul Hoda, Nasir Ali Siddiqui, Abul Kalam Najmi, Mohammad Ahmad","doi":"10.1055/a-2347-9824","DOIUrl":"10.1055/a-2347-9824","url":null,"abstract":"<p><strong>Background and purpose: </strong>SGLT2 inhibitors are class of drugs that are used in adults with type 2 diabetes through a novel mechanism of action by reducing renal tubular glucose reabsorption, leading to a reduction in blood glucose without stimulating insulin release. In this systematic review, we report the effects of treatment with SGLT2 inhibitors on urinary tract infection (UTI) and genitourinary infection (GUI).</p><p><strong>Method: </strong>The study integrated data from landmark trials of SGLT2 inhibitors (CANVAS, CREDENCE, DECLARE-TIMI 58, and EMPA-REG) to interpret the association of SGLT2 inhibitors with genital infection (GI) and UTI. We reported the review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome was a composite of participants reporting UTI and GUI prescribed on SGLT2 inhibitors.</p><p><strong>Results: </strong>The analysis of four studies involving 38,723 participants revealed incidences of both UTIs and GUI. In the SGLT2 inhibitor group, comprising 21,266 participants, 222 (1.04%) experienced UTIs, and 477 (2.24%) reported GUI. In contrast, among the placebo group consisting of 17,457 participants, 201 (1.15%) reported UTIs, and 70 (0.40%) reported genital infections. These findings underscore the elevated risk associated with SGLT2 inhibitor use, particularly regarding GUI, necessitating careful consideration in clinical practice and patient management strategies.</p><p><strong>Conclusion: </strong>The incidence of UTIs and particularly more pronounced GUI associated with SGLT2 inhibitors highlights the importance of careful risk assessment and monitoring in clinical decision-making, underscoring the need for patient management strategies.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"307-313"},"PeriodicalIF":1.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cerebroprotective Potential of Andrographolide Nanoparticles: In silico and In vivo Investigations.","authors":"Lakshmi Charitha Rudrala, Ranadheer Reddy Challa, Sibbala Subramanyam, Sampath Ayyappa Gouru, Gagandeep Singh, N V L Sirisha Mulukuri, Praveen Kumar Pasala, Prasanth Sree Naga Bala Krishna Dintakurthi, Somasekhar Gajula, Mithun Rudrapal","doi":"10.1055/a-2345-5396","DOIUrl":"10.1055/a-2345-5396","url":null,"abstract":"<p><p>Ischemic stroke remains the leading cause of death and disability, while the main mechanisms of dominant neurological damage in stroke contain oxidative stress and inflammation. Docking studies revealed a binding energy of - 6.1 kcal/mol for AG, while the co-crystallized ligand (CCl) exhibited a binding energy of - 7.3 kcal/mol with NOS. AG demonstrated favourable hydrogen bond interactions with amino acids ASN A:354 and ARG A:388 and hydrophobic interactions with GLU A:377. Molecular dynamics simulations throughout 100 ns indicated a binding affinity of - 27.65±2.88 kcal/mol for AG, compared to - 18.01±4.02 kcal/mol for CCl. These findings suggest that AG possesses a superior binding affinity for NOS compared to CCl, thus complementing the stability of NOS at the docked site.AG has limited applications owing to its low bioavailability, poor water solubility, and high chemical and metabolic instability.The fabrication method was employed in the preparation of AGNP, SEM analysis confirmed spherical shape with size in 19.4±5 nm and investigated the neuroprotective effect in cerebral stroke rats induced by 30 min of carotid artery occlusion followed by 4 hr reperfusion, evaluated by infarction size, ROS/RNS <i>via</i> GSH, MPO, NO estimationand AchE activity, and monitoring EEG function. Cortex and hippocampal histology were compared between groups. AGNP treatment significantly decreased Infarction size and increased GSH levels (p<0.01<sup>**</sup>), decreased MPO (p<0.01<sup>**</sup>), NO (p<0.01<sup>**</sup>), AchE (p<0.01<sup>**</sup>), restored to normal EEG amplitude, minimizing unsynchronized polyspikes and histological data revealed that increased pyramidal cell layer thickness and decreased apoptotic neurons in hippocampus, cortex appeared normal neurons with central large vesicular nuclei, containing one or more nucleoli in compared to AG treatment. Based on brain biochemical, histopathology reports AGNP exhibited significant cerebroprotective activity compared to AG on ischemic rats.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"335-346"},"PeriodicalIF":1.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug ResearchPub Date : 2024-09-01Epub Date: 2024-07-11DOI: 10.1055/a-2347-9919
Vishal J Patel, Amit A Joharapurkar, Samadhan G Kshirsagar, Maulik S Patel, Hardikkumar H Savsani, Harshad S Dodiya, Milan H Rakhasiya, Ashvin K Patel, Rajesh Sundar, Mukul R Jain
{"title":"HIF Stabilizer Desidustat Protects against Complement-Mediated Diseases.","authors":"Vishal J Patel, Amit A Joharapurkar, Samadhan G Kshirsagar, Maulik S Patel, Hardikkumar H Savsani, Harshad S Dodiya, Milan H Rakhasiya, Ashvin K Patel, Rajesh Sundar, Mukul R Jain","doi":"10.1055/a-2347-9919","DOIUrl":"10.1055/a-2347-9919","url":null,"abstract":"<p><p>Complement cascade is a defence mechanism useful for eliminating pathogenic microorganisms and damaged cells. However, activation of alternative complement system can also cause inflammation and promote kidney and retinal disease progression. Inflammation causes tissue hypoxia, which induces hypoxia-inducible factor (HIF) and HIF helps the body to adapt to inflammation. In this study, we investigated the effect of HIF stabilizer desidustat in complement-mediated diseases. Oral administration of desidustat (15 mg/kg) was effective to reduce the kidney injury in mice that was induced by either lipopolysaccharide (LPS), doxorubicin or bovine serum albumin (BSA)-overload. Complement activation-induced membrane attack complex (MAC) formation and factor B activity were also reduced by desidustat treatment. In addition, desidustat was effective against membranous nephropathy caused by cationic BSA and retinal degeneration induced by sodium iodate in mice. C3-deposition, proteinuria, malondialdehyde, and interleukin-1ß were decreased and superoxide dismutase was increased by desidustat treatment in cBSA-induced membranous nephropathy. Desidustat specifically inhibited alternative complement system, without affecting the lectin-, or classical complement pathway. This effect appears to be mediated by inhibition of factor B. These data demonstrate the potential therapeutic value of HIF stabilization by desidustat in treatment of complement-mediated diseases.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"325-334"},"PeriodicalIF":1.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug ResearchPub Date : 2024-07-01Epub Date: 2024-07-05DOI: 10.1055/a-2317-7578
Mohammad Rafi Khezri, Reza Varzandeh, Morteza Ghasemnejad-Berenji
{"title":"Concomitant Effects of Metformin and Vitamin C on Indomethacin-Induced Gastric Ulcer in Rats: Biochemical and Histopathological Approach.","authors":"Mohammad Rafi Khezri, Reza Varzandeh, Morteza Ghasemnejad-Berenji","doi":"10.1055/a-2317-7578","DOIUrl":"https://doi.org/10.1055/a-2317-7578","url":null,"abstract":"<p><strong>Introduction: </strong>Gastric ulcer is one of the most common and serious conditions in the gastrointestinal tract. One of the main causes of gastric ulcers is using of non-steroidal anti-inflammatory drugs (NSAIDs) which have limited their use in clinical practice. Several studies have revealed that metformin and Vitamin C (Vit C) exhibit protective effects against gastric mucosal damage in different animal models. However, no studies indicate their combination's effect on gastric ulcer models. Therefore, this study aims to investigate the protective effects of metformin and Vit C combination on indomethacin-induced gastric ulcers.</p><p><strong>Material and methods: </strong>In total, thirty rats were divided into six groups, including the control group, rats received indomethacin (50 mg/kg, i.p.), rats received indomethacin and pretreated with ranitidine (100 mg/kg), metformin (100 mg/kg, i.p.), Vit C (100 mg/kg), or metformin combined with Vit C. Four hours after indomethacin administration, rats were euthanized, and gastric tissues were removed for macroscopic, histopathologic, and biochemical examinations.</p><p><strong>Results: </strong>All therapeutics used in this study were found to alleviate gastric mucosal injury caused by indomethacin, as observed in histopathologic and macroscopic evaluations. Both Vit C and metformin were observed to significantly decrease lipid peroxidation and enhance the activity of anti-oxidative enzymes, SOD, GPx, and catalase. However, a more significant effectiveness was observed in catalase and GPx activities when Vit C was co-administered with metformin.</p><p><strong>Conclusions: </strong>In conclusion, the present study revealed that metformin and Vit C combination therapy could potentially treat gastric ulcers associated with indomethacin.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":"74 6","pages":"280-289"},"PeriodicalIF":1.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}