Naunyn-schmiedebergs Archives of Pharmacology最新文献

{"title":"New phosphodiesterase-4 inhibitors present airways relaxant activity in a guinea pig acute asthma model","authors":"","doi":"10.1007/s00210-023-02905-8","DOIUrl":"https://doi.org/10.1007/s00210-023-02905-8","url":null,"abstract":"<h3>Abstract</h3> <p>Asthma is a disease characterized by chronic inflammation and hyper responsiveness of airways. We aimed to assess the relaxant potential of phosphodiesterase-4 (PDE4) inhibitors N-sulfonilhidrazonic derivatives on non-asthmatic and asthmatic guinea pig trachea. Firstly, guinea pigs were sensitized and challenged with ovalbumin, and then morphological, and contractile changes were evaluated resulting from asthma, followed by evaluation of relaxant effect of derivatives on guinea pig trachea and the cAMP levels measurement by ELISA. It has been evidenced hypertrophy of airway smooth muscle, inflammatory infiltrate, and vascular abnormalities. Moreover, only sensitized tracheal rings were responsive to OVA. Contractile response to histamine, but not to carbachol, was greater in sensitized animals, however the relaxant response to aminophylline and isoprenaline were the same in non-asthmatics and asthmatics. N-sulfonilhidrazonic derivatives presented equipotent relaxant action independent of epithelium, with exception of LASSBio-1850 that presented a low efficacy (&lt; 50%) and LASSBio-1847 with a 4-fold higher potency on asthmatics. LASSBio-1847 relaxant curve was impaired in the presence of propranolol and potentiated by isoprenaline in both groups. Furthermore, relaxation was potentiated 54- and 4-fold by forskolin in non-asthmatics and asthmatics, respectively. Likewise, LASSBio-1847 potentiated relaxant curve of aminophylline 147- and 4-fold in both groups. The PKA inhibitor H-89 impaired the relaxant potency of the derivative. Finally, LASSBio-1847 increased tracheal intracellular cAMP levels similarly to rolipram, selective PDE4 inhibitor, in both animals. LASSBio-1847 showed to be promising to relax guinea pig trachea from non-sensitized and sensitized guinea pigs by activation of β₂-adrenergic receptors/AC/cAMP pathway.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138716549","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":"Presentation of the obsolete drug reserpine in three German-language pharmacology textbooks","authors":"Nikolas Misera, Roland Seifert","doi":"10.1007/s00210-023-02877-9","DOIUrl":"https://doi.org/10.1007/s00210-023-02877-9","url":null,"abstract":"<p>For several decades, reserpine was used to treat hypertension and, to a limited extent, psychoses. Over time, however, the indication became more and more restricted to the point of obsolescence. This study examines the extent to which textbooks are up to date in their content and oriented towards therapeutic guidelines, using the obsolete drug reserpine as a paradigm. Three German pharmacology textbook series were examined for the coverage of reserpine from 1964-2023: <i>Allgemeine und Spezielle Pharmakologie und Toxikologie</i> (Aktories), <i>Allgemeine und Spezielle Pharmakologie und Toxikologie</i> (Karow) and <i>Pharmakologie und Toxikologie</i> (Lüllmann). We compared the textbook content with data on reserpine prescriptions and hypertension guidelines and analysed the relevance of reserpine in examinations using German federal exam questions by the Institute for medical and pharmaceutical exam questions (IMPP). The textbooks differ conceptually from each other. The indication of reserpine for hypertension has become more restricted over time in all three textbooks, yet they partially show discrepancies with hypertension guidelines. The reserpine prescription figures show a strong decline , and reserpine has not been queried by the IMPP, which underlines the obsolescence of the drug. Overall, our study shows that the presentation of a representative obsolete drug in pharmacology textbooks lags current medical practice. We also unmasked more differences in the presentation of an obsolete drug in standard textbooks than anticipated. In conclusion, the analysis of obsolete drugs in pharmacology textbooks is an informative way of assessing how up-to-date they are.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138686973","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":"Population pharmacokinetic modeling of levodropropizine: extended application to comparative analysis between commercial formulations and exploration of pharmacokinetic effects of diet","authors":"Seung-Hyun Jeong, Ji-Hun Jang, Yong-Bok Lee","doi":"10.1007/s00210-023-02889-5","DOIUrl":"https://doi.org/10.1007/s00210-023-02889-5","url":null,"abstract":"<p>Levodropropizine, a nonopioid antitussive agent, is being increasingly used in clinical practice with the development of several formulations for symptomatic relief of acute and chronic bronchitis. However, scientific and quantitative population pharmacokinetic analyses of levodropropizine are lacking. Moreover, no integrated quantitative comparison has been performed between formulations. This study quantitatively evaluated and predicted pharmacokinetic properties of formulations through population pharmacokinetic model–based comparisons of commercially available formulations. Plasma concentration profile results from bioequivalence studies of 60-mg immediate release (IR) levodropropizine tablets in 40 healthy Korean males were used as population pharmacokinetic modeling data. For interindividual variability in levodropropizine pharmacokinetics, body surface area was identified as an effective covariate that was positively correlated with peripheral compartment distribution volume. Population pharmacokinetic model for IR tablets well-described the levodropropizine syrup and capsule datasets, suggesting no significant differences in pharmacokinetics among IR tablets, syrups, and capsules of levodropropizine. In contrast, pharmacokinetic profiles differed between 90-mg controlled release (CR) and IR levodropropizine tablets; however, separate parameter estimation was possible by applying the same model structure. In terms of pharmacokinetics, twice-daily regimen of 90-mg CR tablets was equivalent to thrice-daily regimen of 60-mg IR tablets. However, at steady-state, interindividual plasma concentration variability within population was reduced by approximately 36.71–83.18%. For levodropropizine CR tablets, a high-fat diet significantly delayed gastrointestinal absorption but maintained overall plasma exposure equivalent. This study provides useful quantitative judgment data for precision medicine of levodropropizine and can be helpful in predicting the pharmacokinetics of levodropropizine based on commercialized formulation switching.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138682313","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":"The protective role of l-carnitine on oxidative stress, neurotransmitter perturbations, astrogliosis, and apoptosis induced by thiamethoxam in the brains of male rats","authors":"Heba-Tallah Abd Elrahim Abd Elkader, Marium Marzoq Hussein, Nema A . Mohammed, Heba M . Abdou","doi":"10.1007/s00210-023-02887-7","DOIUrl":"https://doi.org/10.1007/s00210-023-02887-7","url":null,"abstract":"<p>Synthetic organic insecticides such as pyrethroids, organophosphates, neonicotinoids, and others have the potential to disrupt ecosystems and are often toxic to humans. Thiamethoxam (TMX), a neonicotinoid insecticide , is a widely used insecticide with neurotoxic potential. <span>l</span>-Carnitine (LC) is regarded as the “gatekeeper” in charge of allowing long-chain fatty acids into cell mitochondria. LC is an endogenous chemical that is renowned for its prospective biological activity in addition to its role in energy metabolism. This study investigated the protective effects of LC against TMX-induced neurotoxicity in male Wistar rats. For 28 days, animals were divided into four groups and treated daily with either LC (300 mg/kg), TMX (100 mg/kg), or both at the aforementioned doses. Our results revealed marked serum lipid profile and electrolyte changes, declines in brain antioxidants and neurotransmitters (acetylcholine, dopamine, and serotonin levels) with elevations in thiobarbituric acid reactive substances and proinflammatory cytokine levels, as well as acetylcholinesterase and monoamine oxidase brain activity in TMX-treated rats. TMX also increased the expression of caspase-3 and glial fibrillary acidic protein. In contrast, pretreatment with LC attenuated TMX-induced brain injury by suppressing oxidative stress and proinflammatory cytokines and modulating neurotransmitter levels. It also ameliorated the expression of apoptotic and astrogliosis markers. It could be concluded that LC has antioxidant, anti-inflammatory, anti-astrogliosis, and anti-apoptotic potential against TMX neurotoxicity.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>\u0000","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138686850","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":"The evaluation of atorvastatin as an adjunct to fluconazole for the anti-fungal prophylaxis in acute myeloid leukemia: a multicenter, triple-blinded, randomized clinical trial","authors":"Niloufar Saber-Moghaddam, Mohammad Moeini Nodeh, Vahid Ghavami, Hossein Rahimi, Sajjad Ataei Azimi, Mohsen Seddigh-Shamsi, Mostafa Kamandi, Abolghasem Allahyari, Somayeh Sadat Shariatmaghani, Sepideh Elyasi, Omid Arasteh","doi":"10.1007/s00210-023-02892-w","DOIUrl":"https://doi.org/10.1007/s00210-023-02892-w","url":null,"abstract":"<p>The development of invasive fungal infections (IFIs) is a serious complication in acute myeloid leukemia (AML) patients who undergo an induction to remission chemotherapy. Given the increased mortality in AML patients with IFI despite prophylaxis, we need to address this problem. Statins have traditionally been employed in clinical settings as agents for reducing lipid levels. Nonetheless, recent investigations have brought to light their antifungal properties in animals, as well as in vitro studies. The objective of this study was to assess the effectiveness of atorvastatin when added to the routine IFI prophylaxis regimen in patients diagnosed with AML. A randomized, multicenter, triple-blind study was conducted on 76 AML patients aged 18–70, who received either placebo or atorvastatin in addition to fluconazole. Patients were followed for 30 days in case of developing IFIs, patient survival, and atorvastatin- related adverse drug reactions. Data were analyzed with SPSS version 26.0. A level of significance of 0.05 was utilized as the threshold for all statistical tests. The data were analyzed by adjusting for the effect of age, regarding that there was a significant difference between the two groups, and showed that atorvastatin reduced the development of both probable and proven IFI (based on EORTC/MSGERC criteria) compared to placebo. IFI-free survival was also significantly better in the atorvastatin group. The incidence of developing aspergillosis did not differ between the two groups. No serious adverse events related to atorvastatin were observed. The present investigation has substantiated the antecedent in vitro and animal research on the fungicidal impact of statins and has suggested the need for additional research involving larger sample sizes and an extended duration of follow-up. Trial registration: This study was registered on the Iranian registry of clinical trials as IRCT20210503051166N1 (Date of confirmation 2021.05.03).</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"98 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629049","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":"Cubosomes as versatile lipid nanocarriers for neurological disorder therapeutics: a comprehensive review","authors":"Safa A Vahab, Ayushi Nair, Devika Raj, Akhil G P, Sreelakshmi P P, Vrinda S Kumar","doi":"10.1007/s00210-023-02879-7","DOIUrl":"https://doi.org/10.1007/s00210-023-02879-7","url":null,"abstract":"<p>Cubosomes are novel vesicular drug delivery systems with lipidic liquid crystal nanoparticles formed of predetermined proportions of amphiphilic lipids. They have a honeycomb-like structure and are thermodynamically stable. These bicontinuous lipid layers are separated into two water-based channels internally that can be used by various bioactive substances, including drugs, proteins, and peptides. This complex structure is responsible for its high drug-loading capacity. Cubosomes are thought to be promising vehicles for various routes of administration because of their extraordinary characteristics, including bioadhesion, the capacity to encapsulate hydrophilic, and hydrophobic, as well as amphiphilic substances, high resistance to environmental stress, and their ability to achieve controlled release through modification. One of the essential elements for improving patient compliance is the ability of these well-defined nano-drug delivery systems to boost the effectiveness of targeting while lowering the side effects/toxicities of payloads. The large internal surface area, a sufficiently uncomplicated fabrication procedure, and biodegradability make it an attractive nano lipid carrier for drug delivery. This review outlines the recent advancement of cubosomes for managing various neurological disorders, highlighting their potential in this field.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"236 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629557","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":"Comparison of bolus administration and short-term infusion versus long-term infusion of doxorubicin in terms of cardiotoxicity and efficacy","authors":"Hamed Ghiami, Navid Omidkhoda, Mohsen Seddigh-Shamsi, Hossein Rahimi, Omid Arasteh","doi":"10.1007/s00210-023-02886-8","DOIUrl":"https://doi.org/10.1007/s00210-023-02886-8","url":null,"abstract":"<p>Cardiotoxicity caused by anthracyclines chemotherapy is one of the leading causes of mortality and morbidity in cancer survivors. Continuous infusion (CI) instead of bolus (BOL) injection is one of the methods that seem to be effective in reducing doxorubicin (DOX) cardiotoxicity. Due to the variety of results, we decided to compare these two approaches regarding toxicity and efficacy and report the final results for different cancers. We included 21 studies (four preclinical and seventeen clinical trials) up to May 15, 2023. In children with acute lymphoblastic leukemia (ALL) and adults with chronic lymphoblastic leukemia (CLL) and gastric cancer, results were in favor of BOL injection, without increase in cardiotoxicity. On the other hand, CI showed to be better option in patients with small-cell lung cancer (SCLC) and breast cancer. Various results were also observed in adult patients with sarcoma. Overall, it can be concluded that the benefits of CI, especially in adults, outweigh its disadvantages. However, due to the variety of results and heterogeneity of studies, further clinical trials with a larger sample size and a longer duration of follow-up are needed to make a more accurate comparison between CI and BOL injection.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629052","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":"Unveiling innovative therapeutic strategies and future trajectories on stimuli-responsive drug delivery systems for targeted treatment of breast carcinoma","authors":"Israa Habeeb Naser, Muhaned Zaid, Eyhab Ali, Hayder Imad Jabar, Anfal Nabeel Mustafa, Mahmood Hasen Shuhata Alubiady, Montather F. Ramadan, Khursheed Muzammil, Reem Mohsin Khalaf, Sarah Salah Jalal, Ahmed Hussien Alawadi, Ali Alsalamy","doi":"10.1007/s00210-023-02885-9","DOIUrl":"https://doi.org/10.1007/s00210-023-02885-9","url":null,"abstract":"<p>This comprehensive review delineates the latest advancements in stimuli-responsive drug delivery systems engineered for the targeted treatment of breast carcinoma. The manuscript commences by introducing mammary carcinoma and the current therapeutic methodologies, underscoring the urgency for innovative therapeutic strategies. Subsequently, it elucidates the logic behind the employment of stimuli-responsive drug delivery systems, which promise targeted drug administration and the minimization of adverse reactions. The review proffers an in-depth analysis of diverse types of stimuli-responsive systems, including thermoresponsive, pH-responsive, and enzyme-responsive nanocarriers. The paramount importance of material choice, biocompatibility, and drug loading strategies in the design of these systems is accentuated. The review explores characterization methodologies for stimuli-responsive nanocarriers and probes preclinical evaluations of their efficacy, toxicity, pharmacokinetics, and biodistribution in mammary carcinoma models. Clinical applications of stimuli-responsive systems, ongoing clinical trials, the potential of combination therapies, and the utility of multifunctional nanocarriers for the co-delivery of assorted drugs and therapies are also discussed. The manuscript addresses the persistent challenge of drug resistance in mammary carcinoma and the potential of stimuli-responsive systems in surmounting it. Regulatory and safety considerations, including FDA guidelines and biocompatibility assessments, are outlined. The review concludes by spotlighting future trajectories and emergent technologies in stimuli-responsive drug delivery, focusing on pioneering approaches, advancements in nanotechnology, and personalized medicine considerations. This review aims to serve as a valuable compendium for researchers and clinicians interested in the development of efficacious and safe stimuli-responsive drug delivery systems for the treatment of breast carcinoma.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629402","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":"Studies on the mechanism of local and extra-intestinal tissue manifestations in AOM-DSS-induced carcinogenesis in BALB/c mice: role of PARP-1, NLRP3, and autophagy","authors":"Shivani Singla, Gopabandhu Jena","doi":"10.1007/s00210-023-02878-8","DOIUrl":"https://doi.org/10.1007/s00210-023-02878-8","url":null,"abstract":"<p>Colitis-associated colorectal cancer (CACC) is one of the devastating complications of long-term inflammatory bowel disease and is associated with substantial morbidity and mortality. Combination of azoxymethane (AOM) and dextran sulfate sodium (DSS) has been extensively used for inflammation-mediated colon tumor development due to its reproducibility, potency, histological and molecular changes, and resemblance to human CACC. In the tumor microenvironment and extra-intestinal tissues, PARP-1, NLRP3 inflammasome, and autophagy’s biological functions are complicated and encompass intricate interactions between these molecular components. The focus of the present investigation is to determine the colonic and extra-intestinal tissue damage induced by AOM-DSS and related molecular mechanisms. Azoxymethane (10 mg/kg, i.p.; single injection) followed by DSS (3 cycles, 7 days per cycle) over a period of 10 weeks induced colitis-associated colon cancer in male BALB/c mice. By initiating carcinogenesis with a single injection of azoxymethane (AOM) and then establishing inflammation with dextran sulfate sodium (DSS), a two-stage murine model for CACC was developed. Biochemical parameters, ELISA, histopathological and immunohistochemical analysis, and western blotting have been performed to evaluate the colonic, hepatic, testicular and pancreatic damage. In addition, the AOM/DSS-induced damage has been assessed by analyzing the expression of a variety of molecular targets, including proliferating cell nuclear antigen (PCNA), interleukin-10 (IL-10), AMP-activated protein kinase (AMPK), poly (ADP-ribose) polymerase-1 (PARP-1), cysteine-associated protein kinase-1 (caspase-1), NLR family pyrin domain containing 3 (NLRP3), beclin-1, and interleukin-1β (IL-1β). Present findings revealed that AOM/DSS developed tumors in colon tissue followed by extra-intestinal hepatic, testicular, and pancreatic damages.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>\u0000","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629045","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":"Cytoprotective potency of naringin against di-n-butylphthalate (DBP)-induced oxidative testicular damage in male rats","authors":"Anis Anis, Sameh H. El-Nady, Hany A. Amer, Hamed T. Elbaz, Ahmed E. Elweza, Nermeen Borai El-Borai, Salah S. El-Ballal","doi":"10.1007/s00210-023-02874-y","DOIUrl":"https://doi.org/10.1007/s00210-023-02874-y","url":null,"abstract":"<p>The present study aimed to investigate the protective potential of naringin (NG) against di-n-butyl phthalate (DBP)- induced testicular damage and impairment of spermatogenesis in rats. Forty-two male Wistar albino rats were divided into six equal groups, and treated orally, 3 times weekly for 8 successive weeks. Control vehicle group was administrated olive oil, naringin-treated group was administered NG (80 mg/kg), DBP 250- and DBP 500- intoxicated groups received DBP (250 mg/kg) and (500 mg/kg), respectively, NG + DBP 250 and NG + DBP 500 groups received NG, an hour prior to DBP 250 and 500 administration. The results revealed that DBP induced dose-dependent male reproductive dysfunctions, included a significant decrease in the serum testosterone level concomitantly with significant decreases in the sperm count, viability, and total motility. Meanwhile, DBP significantly increased the testicular malondialdehyde level with significant reductions of glutathione content and catalase activity. Histopathologically, DBP provoked absence of spermatozoa, degenerative changes in the cell layers of seminiferous tubules and a significant decrease in the thickness of the seminiferous tubules epithelium. Conversely, the concomitant treatment with NG, one hour before DBP 250 or 500- intoxication mitigated the dose-dependent reproductive dysfunctions induced by DBP, evidenced by significant increases of serum testosterone level, sperm motility, count and viability along with marked improvement of the oxidant/antioxidant status and testicular histoarchitecture. In conclusion, the findings recorded herein proved that NG could mitigate DBP-induced testicular damage and impairment of spermatogenesis, suggesting the perspective of using NG as a natural protective and therapeutic agent for alleviating the reproductive dysfunctions and improving reproductive performance, mainly via its potent antioxidant activity.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"101 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629836","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}