Khaled Abo-EL-Sooud

Liver injury is a globally serious problem that may be observed post-chemotherapeutic administration in chronic crises such as tuberculosis (TB). Rifamycin (RIF), particularly, is an indispensable treatment regimen for TB with a significant negative hepatic impact. Therefore, this research aims to assess the restorative role of melatonin (MEL) against rifampicin (RIF)-associated hepatic damage in rats. Moreover, to investigate the ultimate mechanism of the antioxidant potential of MEL with multimodal assessment and in silico molecular conformation. Adult male Wistar albino rats were weighed and divided into four groups of ten rats each. The control group received the vehicle (0.5 ml/day), the RIF-intoxicated group (100 mg/kg/day orally), the MEL-treated group (10 mg/kg/day intraperitoneally), and the Co-administered RIF and MEL group at the same regimen for 21 consecutive days. Blood and hepatic tissue samples were obtained for biochemical, histological, and molecular studies. High in vitro antioxidant scavenging potential of MEL with an IC of 94.66 µg/ml was attained using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Fourier transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GC-MS) analyses of MEL indicated the presence of mainly cinnamic acid, m-(trimethyl-silyl ester), in addition to several reactive antioxidant moieties. The plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lipid profiles were significantly reduced in the MEL + RIF co-administered group in contrast to the RIF-treated group (P < 0.05). Moreover, MEL significantly decreased the hepatic oxidative biomarkers malondialdehyde (MDA) and significantly increased the estimated antioxidant enzyme levels (P < 0.05) of superoxide dismutase (SOD) and glutathione peroxidase (GPX). Histological evaluations revealed mild hepatic injuries and inflammatory cellular infiltration in MEL-treated animals. Molecular docking explored the high-affinity interaction of MEL and cinnamic acids with hepatic cytochrome P450 isoform 3A4 (CYP3A4) protein target, confirming their hepatic restorative potential. This study endorses the antioxidant potential role of MEL in RIF-hepatic injury.

5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent for solid malignancies. Although it has crucial therapeutic effects, it ranks as the second most cardiotoxic antineoplastic agent. Berberine (BBR) is a quaternary benzylisoquinoline alkaloid with promising antioxidant properties. The current study aimed to assess the palliative effect of BBR on 5-FU-induced cardiotoxicity in rats. Fifty male Sprague Dawley rats were randomly divided into five groups: negative control, which received 2% DMSO orally (PO) for 2 weeks; cardiotoxic, which received a single intraperitoneal (IP) injection of 5-FU (150 mg/kg); groups 3 and 4, which received a single IP injection of 5-FU (150 mg/kg) followed by BBR (50 mg/kg and 100 mg/kg, respectively) PO for 2 weeks; and a BBR-only group, which received BBR (100 mg/kg) PO for 2 weeks. On the 14th day, all groups underwent ECG evaluation. Blood and heart samples were collected 24 h after the last dose for further investigations. 5-FU induced significant alterations in the ECG pattern and caused a significant increase in cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and malondialdehyde (MDA). Moreover, it led to decreased levels of superoxide dismutase (SOD), reduced glutathione (GSH), and total antioxidant capacity (TAC). Our data suggest that BBR could mitigate 5-FU-induced cardiotoxicity by modulating cardiac injury markers, normalizing cTnI, CK-MB, and LDH levels, reducing oxidative stress by lowering MDA levels, and increasing SOD, GSH, and TAC levels. Additionally, BBR inhibited apoptotic events by suppressing caspase-3 activation and upregulating Bcl-2 expression, reduced the inflammatory response by downregulating cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-α) expression levels, and decreased the risk of thrombosis by increasing endothelial nitric oxide synthase (eNOS) expression levels. In conclusion, BBR exerts ameliorative effects against 5-FU-induced cardiotoxicity in rats.

PURPOSE: The antibacterial properties of silver nanoparticles (AgNPs) are extensively identified. In large quantities, they might be harmful. So many fields of nanotechnology have shown a great deal of interest in the development of an environmentally friendly, efficient method for synthesizing metal nanoparticles. Because of its antibacterial and antifungal properties toward a wide range of microbes, chitosan silver nanoparticles (AgNPs@Cs) constitute a newly developing class of bio-nanostructured hybrid materials. Furthermore, the use of photothermal therapy (PTT) has been suggested as a means of elimination of germs. These light-stimulated treatments are minimally invasive and have a few side effects. In the present work, the antibacterial effect of AgNPs at low concentrations; prepared by chemical and green methods as antimicrobial and photothermal agents in photothermal therapy; with laser irradiation were explored as combined treatment against MRSA, Pseudomonas aeruginosa, and Klebsiella pneumoniae.

METHODS: Silver nanoparticles were produced in two ways. First, by sodium borohydrides, second, by chitosan (as a natural eco-friendly reducing, and capping agent). The nanostructure of AgNPs and AgNPs@Cs was confirmed by UV-visible spectrometer, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIRs), and direct light scattering (DLS). The antibacterial activity of the prepared nanoparticles and the laser irradiation was tested against three bacterial species of zoonotic importance; MRSA, Pseudomonas aeruginosa, and Klebsiella pneumoniae; and was evaluated by measuring their minimum inhibitory concentrations (MIC).

RESULTS: Silver nanoparticles produced by the two methods had spherical shapes with nearly the same particle size. The analysis of DLS showed that AgNPs were very stable with zeta potential - 28.8 mv, and 47.7 mv by chemical and chitosan synthesis, respectively. Furthermore, AgNPs@Cs showed higher antibacterial activity toward the tested bacterial species than AgNPs by chemical method. Additionally, the bacterial viability using photothermal laser therapy was reduced compared to laser and AgNPs alone. The bactericidal activities were higher when laser diode was coupled with AgNPs@Cs than by chemical reduction.

CONCLUSION: The laser combined treatment had a higher antimicrobial effect than AgNPs alone or laser irradiation alone.