Iranian Journal of Pharmaceutical Research最新文献

{"title":"Design, Synthesis, Anticonvulsant Evaluation, and Molecular Docking Studies of New GABA_A Agonist Derivatives.","authors":"Mansur Nassiri Koopaei, Parsa Moghimirad, Ebrahim Saeedian Moghadam, Nasrin Nassiri Koopaei, Massoud Amanlou, Tahmineh Akbarzadeh, Mohammad Sharifzadeh, Mohsen Amini","doi":"10.5812/ijpr-157392","DOIUrl":"10.5812/ijpr-157392","url":null,"abstract":"<p><strong>Background: </strong>The side effects and drug resistance associated with current antiepileptic drugs necessitate the design and synthesis of new candidate anticonvulsant agents.</p><p><strong>Objectives: </strong>The present study aimed to design, synthesize, and screen a new series of gamma-aminobutyric acid (GABA) agonist derivatives for the treatment of seizures in an animal model.</p><p><strong>Methods: </strong>The test chemical compounds were synthesized using known synthetic routes, and their structures were confirmed by various spectroscopic methods. Anticonvulsant activity was evaluated using the pentylenetetrazole (PTZ) animal model. Molecular docking studies were conducted to assess interactions with the GABA_A receptor.</p><p><strong>Results: </strong>Some synthesized compounds significantly improved seizure symptoms and reduced mortality rates in the PTZ model. Derivative 3c demonstrated a correlation with the GABA_A receptor in the flumazenil test.</p><p><strong>Conclusions: </strong>The synthesized molecules exhibited moderate to good activity compared to the control group. Derivative 3c notably increased seizure latency relative to the control. Flumazenil inhibitory effect tests indicated that 3c protects against PTZ-induced seizures via the synaptic GABA_A receptor.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e157392"},"PeriodicalIF":1.8,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurobehavioral and Dopaminergic Dysfunctions Induced by Mixed Metal Exposure in C57BL/6 Mice.","authors":"Daeun Lee, Haesoo Kim, Sarita Pyatha, Kisok Kim","doi":"10.5812/ijpr-158559","DOIUrl":"10.5812/ijpr-158559","url":null,"abstract":"<p><strong>Background: </strong>Aluminum (Al), lead (Pb), and mercury (Hg) are major environmental pollutants, and a large population may be simultaneously exposed to these metals. However, studies on the potential neurobehavioral effects of mixed exposure to Al, Pb, and Hg are lacking.</p><p><strong>Objectives: </strong>This study aimed to evaluate neurobehavioral changes in mice following combined exposure to Al, Pb, and Hg and to investigate the effects of this exposure on dopaminergic neurotransmission within the striatum.</p><p><strong>Methods: </strong>In this study, C57BL/6 mice (n = 10 per group) were assigned to control and metal-treated groups. Changes in motor coordination and locomotor activity that occurred when mice were simultaneously exposed to these metals via drinking water for 28 days were measured using the rotarod and open field tests. In addition, dopamine content and key factors involved in dopaminergic neurotransmission in the striatum were evaluated using real-time PCR and Western blot analysis.</p><p><strong>Results: </strong>The mixed metal exposure decreased motor function and significantly reduced the content of dopamine in the striatum of the experimental mice (P < 0.001). Expression of tyrosine hydroxylase, vesicular monoamine transporter 2, and dopamine receptor D1, which are involved in dopaminergic neurotransmission in the striatum, was significantly decreased (P < 0.01), whereas expression of the dopamine transporter was significantly increased (P < 0.05). Dopamine receptor D2 expression was not significantly changed by the mixed metal exposure.</p><p><strong>Conclusions: </strong>These results suggest that mixed exposure to Al, Pb, and Hg inhibits normal dopaminergic neurotransmission, resulting in neurobehavioral disorders.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e158559"},"PeriodicalIF":1.8,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Bioactivity Investigation of Novel 2-({2-[(Dialkylamino) Methyl] Quinazolin-4-one-3-yl} Methyl) Benzonitrile Derivatives as Dipeptidyl Peptidase-4 Inhibitory Agent.","authors":"Arif Arrahman, Noer Luthfianeu Edsyah, Theresia Thiofani, Hanifah Sakinatun Khalidah, Laila Fauziah, Anjani Widyasintia, Benson Benson, Kevin Tanu Putra, Hayun Hayun","doi":"10.5812/ijpr-145406","DOIUrl":"10.5812/ijpr-145406","url":null,"abstract":"<p><strong>Background: </strong>Quinazolinone derivatives have been documented to exhibit antidiabetic properties via the mechanism of dipeptidyl peptidase-4 (DPP-4) inhibition.</p><p><strong>Objectives: </strong>To prepare and investigate the DPP-4 inhibitory activity in vitro and in silico of a series of novel 2-({2-[(dialkylamino)methyl]quinazolin-4-one-3-yl}methyl)benzonitrile derivatives.</p><p><strong>Methods: </strong>The compounds were synthesized, and the chemical structures were confirmed through spectroscopic techniques. The in vitro DPP-4 inhibitory activity was assessed using an assay kit. Additionally, an in silico study was conducted using molecular docking methods to analyze the occurring binding interactions.</p><p><strong>Results: </strong>The title compounds exhibited good inhibition against DPP-4 enzyme activity (IC₅₀: 1.4621 to 6.7805 µM). Among the compounds studied, the compound having morpholino-methyl substituted at C-2 (5d) exhibited the highest potency in DPP-4 inhibitory activity. Their activities were lower than sitagliptin as the reference standard with IC₅₀: 0.0236 µM and lead compound. In the in silico study, the compounds bound against the DPP-4 enzyme, with affinity values similar to those of sitagliptin. However, only compound 5f showed an interaction orientation and amino acid residues that were somewhat similar to those observed in the interaction between the DPP-4 enzyme and sitagliptin, as well as in the interaction between the DPP-4 enzyme and the lead compound.</p><p><strong>Conclusions: </strong>A series of novel 2-({2-[(dialkylamino)methyl]quinazolin-4-one-3-yl}methyl)benzonitrile derivatives have been synthesized successfully. All the synthesized compounds had lower DPP-4 inhibitory activity than sitagliptin and the lead compound. The lower bioactivity was predicted due to the differences in the interaction between the synthesized and lead compounds against the DPP-4 enzyme.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e145406"},"PeriodicalIF":1.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating The Therapeutic Effect of 2-Nitroimidazole on <i>Toxoplasma gondii</i>: An In vitro and In vivo Study Using BALB/c Mice.","authors":"Elaheh Ghiasipour, Javid Sadraei, Fatemeh Ghaffarifar","doi":"10.5812/ijpr-157086","DOIUrl":"10.5812/ijpr-157086","url":null,"abstract":"<p><strong>Background: </strong>Toxoplasmosis, caused by the protozoan parasite <i>Toxoplasma gondii</i>, remains a significant health concern due to its widespread prevalence and severe impact on immunocompromised individuals. Current treatments are limited, necessitating the exploration of new therapeutic agents.</p><p><strong>Objectives: </strong>This study aimed to evaluate the efficacy and safety of 2-nitroimidazole as a potential treatment for toxoplasmosis in BALB/c mice, comparing its effects with the standard treatment, sulfadiazine.</p><p><strong>Methods: </strong>In vitro assays were conducted to determine the half-maximal inhibitory concentration (IC50) of 2-nitroimidazole and sulfadiazine against <i>T. gondii</i> tachyzoites. The MTT assay was used to assess the cytotoxicity of 2-nitroimidazole on macrophages. In vivo experiments involved treating BALB/c mice infected with <i>T. gondii</i> with either 2-nitroimidazole or sulfadiazine, monitoring survival rates and therapeutic outcomes.</p><p><strong>Results: </strong>In vitro results revealed IC50 values of 5.43 μM for 2-nitroimidazole and 2.99 μM for sulfadiazine, indicating potent anti-tachyzoite activity. The MTT assay showed that 2-nitroimidazole had low cytotoxicity, with significant cell viability even at higher concentrations. Based on the MTT assay findings, 40 μM of 2-nitroimidazole showed the highest level of toxicity towards macrophages. Furthermore, flow cytometry analysis revealed that this compound induced apoptosis in approximately 58.9% of tachyzoites. In vivo, all mice in the control group died by the eighth day. Treatment with sulfadiazine resulted in two mice surviving until the 14th day, while 2-nitroimidazole treatment saw one mouse surviving to the same day. These findings suggest that 2-nitroimidazole has comparable efficacy to sulfadiazine with potentially fewer side effects.</p><p><strong>Conclusions: </strong>The study demonstrates that 2-nitroimidazole is a promising candidate for the treatment of toxoplasmosis, exhibiting strong anti-parasitic activity and low cytotoxicity. Further research is warranted to optimize dosing regimens and explore combination therapies to enhance its therapeutic potential.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e157086"},"PeriodicalIF":1.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and Characterization of Ricin Based Immunotoxins Against EPHA2 Receptor for Breast Cancer Therapy: An In-Silico Study.","authors":"Atefeh Faraz, Jafar Amani, Sedigheh Arbabian, Shohreh Zare Karizi, Maryam Bikhof Torbati","doi":"10.5812/ijpr-151574","DOIUrl":"10.5812/ijpr-151574","url":null,"abstract":"<p><strong>Background: </strong>One of the most promising strategies to combat cancer is the use of immunotoxins.</p><p><strong>Objectives: </strong>This study aimed to design two immunotoxins composed of antibody fragments against the EphA2 receptor, which is highly expressed in breast cancer.</p><p><strong>Methods: </strong>EphA2-N-ricin and EphA2-C-ricin were designed by fusing scFv against the EphA2 receptor with the A chain of ricin in varying orders. mFold was used to analyze the mRNA stability of the constructs. The 2D and 3D protein structures of the constructs were predicted using prediction tools and verified by quality assessment tools. The physicochemical properties were calculated using ProtParam. Docking between the constructs and the EphA2 receptor was performed using HADDOCK software, and the 2D interaction plots of the complexes were generated using LigPlus. A 100 ns molecular dynamics (MD) simulation was conducted for docked complexes using Gromacs. Ultimately, the allergenicity and antigenicity of the constructs were determined.</p><p><strong>Results: </strong>The designed immunotoxins had stable mRNAs, reliable 2D and 3D protein structures, and demonstrated high affinity and stable interactions with the receptor protein, as revealed by docking and MD analyses. Higher binding affinity and stability were observed for construct 2. Moreover, the designed immunotoxins lacked allergenicity and were identified as antigens.</p><p><strong>Conclusions: </strong>Based on these observations, it is reasonable to conclude that both designed immunotoxins could serve as suitable immunotoxins; however, construct 2 exhibits more promising properties. Given these results, these immunotoxins could be used in empirical studies to treat breast cancer in vitro or in vivo.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e151574"},"PeriodicalIF":1.8,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genistein Exerts Anti-proliferative Effects by Regulating Apoptosis and Autophagy-Related Genes and MicroRNAs in Human Urinary Bladder Neoplasm EJ138 Cells: An Experimental and Bioinformatic Study.","authors":"Alireza Ziyabakhsh, Mohammad Amin Vatankhah, Farid Pakizeh, Ali Nosrat, Pouria Sobhi, Mohammad Vakili Ojarood, Sina Seifimansour","doi":"10.5812/ijpr-157853","DOIUrl":"10.5812/ijpr-157853","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer (BC) is the most prevalent urogenital malignancy. Recently, the combination of natural compounds with chemotherapeutic agents has gained attention. Genistein, a natural flavonoid, exhibits anti-cancer properties and represents a promising candidate for treating various cancerous cells due to its cytotoxic potential and minimal adverse effects.</p><p><strong>Objectives: </strong>This study aimed to evaluate the anti-cancer effects of genistein by regulating potential target genes and microRNAs involved in apoptosis and autophagy in EJ138 BC cells.</p><p><strong>Methods: </strong>EJ138 BC cells were treated with different concentrations of genistein, and cell viability was assessed using the MTT assay. To determine the apoptotic rate of EJ138 BC cells following genistein treatment, flow cytometry with Annexin V/PI staining was performed. Additionally, real-time PCR was conducted to analyze the expression of miR-27a, miR-151, apoptotic genes (caspase-3, caspase-9), and autophagic genes (ATG12, Beclin1) after 48 hours of genistein treatment. Statistical analysis was carried out using SPSS V.22, with independent t-tests and one-way ANOVA. Results were considered statistically significant at P < 0.05.</p><p><strong>Results: </strong>Our findings demonstrated that genistein inhibited the proliferation, growth, and viability of EJ138 BC cells and induced cell death. Real-time PCR results confirmed that genistein significantly upregulated miR-27a (P < 0.01), ATG12 (P < 0.01), Beclin1 (P < 0.05), caspase-3 (P < 0.001), and caspase-9 (P < 0.0001), while downregulating miR-151 expression (P < 0.05).</p><p><strong>Conclusions: </strong>The results of this study suggest that genistein suppresses the proliferation and growth of human BC cells by modulating genes and microRNAs involved in apoptosis and autophagy. Therefore, genistein may serve as a novel therapeutic agent for BC treatment.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e157853"},"PeriodicalIF":1.8,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the Efficacy and Safety of Sublingual Melatonin on Symptom Severity, Quality of Life, and Sleep Disorders in Patients with Irritable Bowel Syndrome.","authors":"Shabnam Shahrokh, Niloofar Namazi, Mohammad Abbasinazari, Ali Abazarikia, Amir Sadeghi, Arash Mahboubi","doi":"10.5812/ijpr-156425","DOIUrl":"10.5812/ijpr-156425","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have demonstrated the efficacy of melatonin in alleviating symptoms of irritable bowel syndrome (IBS) and improving quality of life (QoL).</p><p><strong>Objectives: </strong>Due to its superior bioavailability, this trial was designed to compare the effects of sublingual melatonin (SL melatonin) with a placebo in alleviating IBS symptoms, enhancing QoL, and addressing sleep disorders.</p><p><strong>Methods: </strong>The IBS patients were randomly assigned to receive either 3 mg of SL melatonin or a matching placebo for eight weeks. Participants completed the IBS symptom severity score (IBS-SSS), IBS-quality of life 34 items (IBS-QoL 34), and Pittsburgh Sleep Quality Index (PSQI) questionnaires immediately before and after the study period.</p><p><strong>Results: </strong>A total of 76 patients completed the trial over six months. The results indicated that the severity of IBS symptoms and QoL scores were significantly better in the SL melatonin group compared to the placebo group (P = 0.032 and P = 0.045, respectively). No participants withdrew from the trial due to serious side effects in either the SL melatonin or placebo groups.</p><p><strong>Conclusions: </strong>Sublingual melatonin may be administered to IBS patients as a complementary treatment to alleviate symptoms and improve QoL.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e156425"},"PeriodicalIF":1.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combinatorial Effects of Chrysin with Doxorubicin, 5-Fluorouracil, and Cyclophosphamide on Triple-Negative Breast Cancer Cell Line.","authors":"Sedighe Yosefi, Hamid Madanchi, Abbas Pakdel, Parviz Kokhaei, Maral Hemati, Negar Sarmadi, Majid Sirati-Sabet","doi":"10.5812/ijpr-157446","DOIUrl":"10.5812/ijpr-157446","url":null,"abstract":"<p><strong>Background: </strong>The primary challenges associated with chemotherapy treatment include the development of drug resistance. Chrysin (CH) has the potential to enhance the therapeutic efficacy of conventional chemotherapeutic agents. Additionally, CH, with its antioxidant properties, can reduce the side effects caused by reactive oxygen species (ROS) from chemotherapy.</p><p><strong>Objectives: </strong>This study focused on investigating the combination impact of CH with either 5-fluorouracil (5-FU), doxorubicin (DOX), or cyclophosphamide (CP) on the triple-negative breast cancer (TNBC) MDA-MB-231 cell line.</p><p><strong>Methods: </strong>Cytotoxicity was investigated using the MTT assay. The checkerboard microplate method was utilized to determine the effects of drug interactions. Apoptosis and cell cycle distribution were measured by flow cytometry. The classical scratch assay was used to examine cell migration ability.</p><p><strong>Results: </strong>The combination of 5-FU and DOX showed synergistic effects with CH (FIX < 1). Conversely, the interaction between CH and CP resulted in non-additive effects (FIX > 1). The combination treatment of CH with a chemotherapeutic drug was more effective in inducing early apoptosis than the drug alone and the control (P < 0.05). An increase in the sub-G1 phase was observed upon treatment with the combination of CH and chemotherapeutic drugs compared with the control and drugs alone (P < 0.05). Co-administration of CH with chemotherapeutic drugs induced a significant decrease in cell migration compared with the control and chemotherapeutic drugs alone (P < 0.05).</p><p><strong>Conclusions: </strong>The results revealed that combination therapy involving CH in conjunction with 5-FU and DOX demonstrated a more substantial therapeutic effect on TNBC cells than treatments with 5-FU and DOX individually.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e157446"},"PeriodicalIF":1.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perioperative Use of Pregabalin vs. Duloxetine for Pain Management of Knee Fracture Surgery: A Double-Blind Randomized Clinical Trial.","authors":"Mohadeseh Masoumi, Mohammad Soleimani, Tara Shekari, Maryam Alaei, Mehrdad Sheikhvatan, Mojtaba Mojtahedzadeh, Kamal Basiri, Farhad Najmeddin, Seyyed Hossein Shafiei","doi":"10.5812/ijpr-157958","DOIUrl":"10.5812/ijpr-157958","url":null,"abstract":"<p><strong>Background: </strong>Effective postoperative pain management, particularly in orthopedic procedures, presents significant challenges. There is increasing evidence supporting the benefits of multimodal analgesia, including the use of gabapentinoids and serotonin norepinephrine reuptake inhibitors (SNRIs), to minimize opioid consumption while effectively managing pain. However, a gold-standard treatment has not been established.</p><p><strong>Objectives: </strong>This study aims to compare the efficacy of duloxetine and pregabalin within a multimodal analgesic regimen for managing postoperative pain and their opioid-sparing effects following knee fracture surgery.</p><p><strong>Methods: </strong>In this double-blind randomized clinical trial (RCT), 54 patients undergoing knee fracture surgery were randomized to receive either 75 mg oral pregabalin or 30 mg duloxetine twice daily, starting at least 24 hours prior to surgery and continuing up to 48 hours postoperatively. Pain severity was assessed at admission and at 6, 12, 24, and 48 hours post-operation. Patients reporting a pain score greater than six on a Numeric Rating Scale (NRS) received intramuscular morphine. Additionally, total opioid dose, associated complications, and drug adverse effects were monitored within the first 48 hours post-surgery.</p><p><strong>Results: </strong>Although there was no statistically significant difference between the duloxetine and pregabalin groups at each time point, the reduction in pain at the 48-hour mark was more pronounced in the duloxetine group compared to the pregabalin group. The duloxetine group required higher doses of morphine on the first day compared to the pregabalin group (3.96 ± 3.20 mg vs. 2.14 ± 2.72 mg, P = 0.022). However, on the second day, opioid rescue was required in three patients in the pregabalin group, whereas no patients in the duloxetine group required rescue. No clinically significant adverse effects were observed in either group.</p><p><strong>Conclusions: </strong>Duloxetine 60 mg per day is an equally effective perioperative alternative to pregabalin 150 mg per day, resulting in a slight increase in rescue opioid administration with equivalent analgesic efficacy during the first 24 hours postoperatively. It demonstrates notable analgesic outcomes with no increased need for opioids between 24 to 48 hours post-surgery.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e157958"},"PeriodicalIF":1.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Protective Effects of Mitochondrial Therapy Against Vincristine- Induced Nephrotoxicity in the Rat's Renal Proximal Tubular Cells.","authors":"Armaghan Lohrasbi, Abdollah Arjmand, Farzaneh Kamranfar, Mehdi Aghsami, Jalal Pourahmad","doi":"10.5812/ijpr-159628","DOIUrl":"10.5812/ijpr-159628","url":null,"abstract":"<p><strong>Background: </strong>The application of vincristine (VCR) in treating a range of cancers is well-documented, showcasing its considerable effectiveness. Nevertheless, its clinical application is constrained by its impact on healthy tissues and various organ systems. Specifically, it can compromise kidney function, resulting in toxicological concerns. Studies have demonstrated that vincristine contributes to nephrotoxicity via the induction of oxidative stress.</p><p><strong>Objectives: </strong>The present research focused on assessing the influence of mitochondrial transplantation in mitigating the mitochondrial and cellular toxicity associated with VCR in renal proximal tubular cells (RPTCs).</p><p><strong>Methods: </strong>This investigation evaluated specific toxicity metrics, including cell death, reactive oxygen species (ROS) generation, decreased mitochondrial membrane potential (MMP), glutathione (GSH) concentration, succinate dehydrogenase (SDH) activity, lipid peroxidation (LPO), and adenosine triphosphate (ATP) levels. Freshly prepared active mitochondria were obtained from the kidneys of Wistar rats.</p><p><strong>Results: </strong>The data demonstrated the cytotoxic effects of VCR on RPTCs. It was further observed that vincristine triggered oxidative stress, characterized by heightened ROS levels, diminished GSH content, decreased SDH activity, and increased lipid peroxidation. Furthermore, VCR caused notable damage to both mitochondrial and lysosomal membranes, along with a significant decrease in ATP content. The innovative strategy of mitochondrial transplantation mitigated oxidative stress, alleviated mitochondrial membrane damage, and prevented ROS-mediated apoptosis signaling induced by vincristine in RPTCs. Our results also indicated an increase in ATP levels within these cells.</p><p><strong>Conclusions: </strong>Our investigation suggests that the proposed treatment modality may prove beneficial in addressing drug-induced nephrotoxicity.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e159628"},"PeriodicalIF":1.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}