Assessment of nebivolol efficacy in experimental models of toxoplasmosis: insights into parasite burden reduction and neuronal protection

被引:1
作者
Ramos, Amanda Bruno da Silva Bellini [1 ]
Torres, Tayline [2 ]
dos Reis, Luis Felipe Cunha [3 ]
Lambert, Gabriel Carvalho [1 ]
Colombo, Fabio Antonio [1 ]
Marques, Marcos Jose [1 ]
Reimao, Juliana Quero [2 ]
机构
[1] Univ Fed Alfenas, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, Alfenas, Brazil
[2] Fac Med Jundiai, Lab Preclin Assays & Res Alternat Sources Innovat, Jundiai, Brazil
[3] Univ Fed Alfenas, Dept Biol Estrutural, Inst Ciencias Biomed, Alfenas, Brazil
关键词
Toxoplasmosis; Nebivolol; In vivo; Neuronal protection; Chronic Toxoplasmosis; Experimental models; GONDII;
D O I
10.1007/s00436-024-08318-7
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
This study investigates the efficacy of nebivolol (NBV) in experimental models of toxoplasmosis, focusing on parasite burden reduction and neuronal protection. In the acute model of experimental toxoplasmosis, Swiss mice infected with RH strain tachyzoites received oral NBV chlorhydrate doses of 2 mg/kg/day and 4 mg/kg/day for 8 days. Treatment with NBV significantly reduced parasite burden compared to vehicle and standard drug (PYR) groups. In the chronic model of experimental toxoplasmosis, C57/BL6 mice infected with the ME49 strain received NBV chlorhydrate 41 days post-infection and were evaluated after 10 days of treatment. NBV chlorhydrate effectively reduced cyst number and area, as well as bradyzoite burden compared to controls. Histological analysis demonstrated that NBV chlorhydrate preserved neuronal count, with the 4 mg/kg/day dose yielding counts similar to non-infected mice. Statistical analysis confirmed significant differences compared to control groups. Furthermore, immunohistochemical analysis revealed a significant reduction in iNOS labeling in the brains of mice treated with NBV chlorhydrate, indicating a decrease in nitric oxide production compared to control groups. These findings suggest NBV's potential as a promising candidate for toxoplasmosis treatment, highlighting its ability to reduce parasite burden and protect neuronal integrity. Further research is warranted to elucidate NBV's mechanisms of action and its clinical application in managing toxoplasmosis.
引用
收藏
页数:10
相关论文
共 26 条
[1]   Screening of GPCR drugs for repurposing in breast cancer [J].
Abdulkareem, Noor Mazin ;
Bhat, Raksha ;
Powell, Reid T. ;
Chikermane, Soumya ;
Yande, Soham ;
Trinh, Lisa ;
Abdelnasser, Hala Y. ;
Tabassum, Mantasha ;
Ruiz, Alexis ;
Sobieski, Mary ;
Nguyen, Nghi D. ;
Park, Jun Hyoung ;
Johnson, Camille A. ;
Kaipparettu, Benny A. ;
Bond, Richard A. ;
Johnson, Michael ;
Stephan, Clifford ;
Trivedi, Meghana V. .
FRONTIERS IN PHARMACOLOGY, 2022, 13
[2]   Immunomodulatory, Antioxidant, and Anti-Inflammatory Activities of Green Synthesized Copper Nanoparticles for Treatment of Chronic Toxoplasma gondii Infection [J].
Alanazi, Abdullah D. ;
Alnomasy, Sultan F. .
PHARMACEUTICALS, 2023, 16 (11)
[3]   Adverse Event Profile of Pyrimethamine-Based Therapy in Toxoplasmosis: A Systematic Review [J].
Ben-Harari, Ruben R. ;
Goodwin, Elizabeth ;
Casoy, Julio .
DRUGS IN R&D, 2017, 17 (04) :523-544
[4]  
Cockcroft J, 2007, VASC HEALTH RISK MAN, V3, P909
[5]   Comprehensive Overview of Toxoplasma gondii-Induced and Associated Diseases [J].
Daher, Darine ;
Shaghlil, Ahmad ;
Sobh, Eyad ;
Hamie, Maguy ;
Hassan, Malika Elhage ;
Moumneh, Mohamad Bahij ;
Itani, Shaymaa ;
El Hajj, Rana ;
Tawk, Lina ;
El Sabban, Marwan ;
El Hajj, Hiba .
PATHOGENS, 2021, 10 (11)
[6]  
Damião B., 2021, Braz. J. Biol., V81, P537, DOI [10.1590/1519-6984.224642, 10.1590/1519-6984.224642]
[7]   Are bipolar disorder, major depression, and suicidality linked with Toxoplasma gondii? A seromolecular case-control study [J].
Demirel, Omer Faruk ;
Akgul, Ozer ;
Bulu, Ersel ;
Aydin, Ezgi Tanriover ;
Cesur, Nuray Uysal ;
Poyraz, Cana Aksoy ;
Oner, Yasar Ali .
POSTGRADUATE MEDICINE, 2023, 135 (02) :179-186
[8]   Repurposing the Medicines for Malaria Venture's COVID Box to discover potent inhibitors of Toxoplasma gondii, and in vivo efficacy evaluation of almitrine bismesylate (MMV1804175) in chronically infected mice [J].
dos Santos, Bruna Ramos ;
Ramos, Amanda Bruno da Silva Bellini ;
de Menezes, Renata Priscila Barros ;
Scotti, Marcus Tullius ;
Colombo, Fabio Antonio ;
Marques, Marcos Jose ;
Reimao, Juliana Quero .
PLOS ONE, 2023, 18 (07)
[9]   Toxoplasmosis - A Global Threat. Correlation of Latent Toxoplasmosis with Specific Disease Burden in a Set of 88 Countries [J].
Flegr, Jaroslav ;
Prandota, Joseph ;
Sovickova, Michaela ;
Israili, Zafar H. .
PLOS ONE, 2014, 9 (03)
[10]   A Review of Nebivolol Pharmacology and Clinical Evidence [J].
Fongemie, Justin ;
Felix-Getzik, Erika .
DRUGS, 2015, 75 (12) :1349-1371