Search

Our previous study showed that dithiophenolate (DTP) and its chitosan nanoparticles (DTP-CSNPs) have abilities to bind with DNA helixes. So in this study, their lethal doses (LD 50 ) and therapeutic roles against rat liver injuries induced by carbon tetrachloride (CCl 4 ) were evaluated. The study focused on the determination of the markers of oxidative stress (OS) and apoptosis and compare the results with those of cisplatin treatment. The results revealed that LD 50 values of DTP and DTP-CSNPs are 2187.5 and 1462.5 mg/kg, respectively. Treatment with DPT and DPT-CSNPs after CCl 4 administration reduced liver injuries, induced by CCl 4 , and improved liver functions and architecture through the reduction of OS and apoptosis. Where the oxidant marker was decreased with elevations of antioxidant markers. Also, there was an elevation in Bcl-2 value, with decreases in caspase-8, Bax, and Bax/Bcl-2 ratio. DPT-CSNPs treatment gave preferable results than those treated with DPT. Moreover, DTP and DPT-CSNPs treatment gave better results than cisplatin treatment. The administration of healthy rats with low doses of DTP and DTP-CSNPs for 14 days had no effect. Otherwise, the study on HepG2 cell line showed that DTP and DPT-CSNPs inhibited cell growth by arresting cells in the G2/M phase and inducing cell death. In conclusion, DTP and DTP-CSNPs have antiapoptotic and anti-oxidative stress toward hepatotoxicity induced by CCl 4 . Moreover, DTP and DTP-CSNPs have anticancer activity against the HepG2 cell line. Generally, DTP-CSNPs are more effective than DTP. So, they can be used in the pharmacological fields, especially DTP-CSNPs., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: A novel coronavirus (COVID-19) that has not been previously identified in humans and has no specific treatment has recently spread. Treatment trials using antiviral and immune-modulating drugs such as hydroxychloroquine (HCQ) were used to control this viral outbreak however several side effects have emerged. Berberine (BER) is an alkaloid that has been reported to reveal some pharmacological properties including antioxidant and antimicrobial activities. Additionally, Zinc oxide nanoparticles (ZnO-NPs) possess potent antioxidant and anti-inflammatory properties. Therefore, this study was undertaken to estimate the efficiency of both BER and synthetic ZnO/BER complex as an anti-COVID-19 therapy., Methods: First, the ZnO/BER complex was prepared by the facile mixing method. Then in vitro studies on the two compounds were conducted including VeroE6 toxicity, anti-COVID-19 activity, determination of inhibitory activity towards papain-like proteinase (PL pro) and spike protein- and receptor- binding domain (RBD) as well as assessment of drug toxicity on RBCs., Results: The results showed that ZnO/BER complex acts as an anti-COVID-19 by inhibiting spike protein binding with angiotensin-converting enzyme II (ACE II), PL pro activity, spike protein and E protein levels, and expression of both E-gene and RNA dependent RNA polymerase (RdRp) at a concentration lower than that of BER or ZnO-NPs alone. Furthermore, ZnO/BER complex had antioxidant and antimicrobial properties where it prevents the auto oxidation of 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and the culture of lower respiratory system bacteria that affected Covid 19 patients. The ZnO/BER complex prevented as well the HCQ cytotoxic effect on both RBC and WBC (in vitro) and hepatotoxicity, nephrotoxicity and anemia that occurred after HCQ long administration in vivo., Conclusion: The ZnO/BER complex can be accounted as promising anti-COVID 19 candidate because it inhibited the virus entry, replication, and assembly. Furthermore, it could be used to treat a second bacterial infection that took place in hospitalized COVID 19 patients. Moreover, ZnO/BER complex was found to eliminate the toxicity of long-term administration of HCQ in vivo ., Competing Interests: Conflict of interestAll authors (D.A. Ghareeb, S.R. Saleh, M.G. Seadawy, M.S. Nofal, S.A. Abdulmalek, S.F. Hassan, S.M. Khedr, M.G. AbdElwahab, A.A. Sobhy, A.A. Abdel-Hamid, A.M. Yassin, A.A.A. Elmoneam, A.A. Masoud, M.M.Y. Kaddah, S.A. El-Zahaby, A.M. Al-mahallawi, A.M. El-Gharbawy, A. Zaki, I.K. Seif, M.Y. Kenawy, M. Amin, K. Amer, M.A. El Demellawy) declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper., (© The Korean Society of Pharmaceutical Sciences and Technology 2021.)