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Infected wounds pose a significant challenge in healthcare, requiring innovative therapeutic strategies. Therefore, there is a critical need for innovative pharmaceutical materials to improve wound healing and combat bacterial growth. This study examined the efficacy of azithromycin-loaded silver nanoparticles (AZM-AgNPs) in treating infected wounds. AgNPs synthesized using a green method with Quinoa seed extract were loaded with AZM. Characterization techniques, including X-ray Powder Diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), and Uv-Vis analysis were utilized. The agar diffusion assay and determination of the MIC were used to assess the initial antibacterial impact of the formulations on both MRSA and E. coli. In addition, the antimicrobial, wound-healing effects and histological changes following treatment with the AZM-AgNPs were assessed using an infected rat model. The nanoparticles had size of 24.9 ± 15.2 nm for AgNPs and 34.7 ± 9.7 nm for AZM-AgNPs. The Langmuir model accurately characterized the adsorption of AZM onto the AgNP surface, indicating a maximum loading capacity of 162.73 mg/g. AZM-AgNPs exhibited superior antibacterial properties in vivo and in vitro compared to controls. Using the agar diffusion technique, AZM-AgNPs showed enhanced zones of inhibition against E. coli and MRSA, which was coupled with decreased MIC levels. In addition, in vivo studies showed that AZM-AgNP treated rats had the best outcome characterized by improved healing process, lower bacterial counts and superior epithelialization, compared to the control group. In conclusion, AZM-AgNPs can be synthesized using a green method with Quinoa seed with successful loading of azithromycin onto silver nanoparticles. In vitro and in vivo studies suggest the promising use of AZM-AgNPs as an effective therapeutic agent for infected wounds.

Background: Heavy metals can cause serious health problems that affect different organs. Cadmium (Cd) is an environmental contaminant known for its toxicological consequences on different organs. Hepatotoxicity is a serious effect of exposure to Cd with oxidative stress (OS) and inflammation playing a central role. Diallyl disulfide (DADS), an organo-sulfur compound found in garlic, is known for its cytoprotective and antioxidant effects. In this study, the effect of DADS on Cd-induced inflammation, oxidative stress and liver injury was investigated. Methods: DADS was supplemented for 14 days via oral gavage, and a single intraperitoneal dose of Cd (1.2 mg/kg body weight) was administered to rats on day 7. Blood and liver samples were collected at the end of the experiment for analyses. Results: Cd administration resulted in remarkable hepatic dysfunction, degenerative changes, necrosis, infiltration of inflammatory cells, collagen deposition and other histopathological alterations. Cd increased liver malondialdehyde (MDA) and nitric oxide (NO) (p < 0.001), upregulated toll-like receptor (TLR)-4, nuclear factor-kappaB (NF-κB), pro-inflammatory mediators, and caspase-3 (p < 0.001) whereas decreased glutathione (GSH) and antioxidant enzymes (p < 0.001). Cd downregulated peroxisome proliferator activated receptor gamma (PPARγ), a transcription factor involved in inflammation and OS suppression (p < 0.001). DADS ameliorated liver injury and tissue alterations, attenuated OS and apoptosis, suppressed TLR-4/NF-κB signaling, and enhanced antioxidants. In addition, DADS upregulated PPARγ in the liver of Cd-administered rats. Conclusions: DADS is effective against Cd-induced hepatotoxicity and its beneficial effects are linked to suppression of inflammation, OS and apoptosis and upregulation of PPARγ. DADS could be valuable to protect the liver in individuals at risk of Cd exposure, pending further studies to elucidate other underlying mechanism(s).

Meloxicam has shown significant neuroprotection in experimental models of stroke, Alzheimer’s disease, and Parkinson’s disease. However, the potential of meloxicam to treat depression-like neuropathology in a chronic restraint stress (CRS) model and the associated molecular changes has been insufficiently explored. The current work aimed to explore the potential neuroprotective actions of meloxicam against CRS-evoked depression in rats. In the current experiments, animals received meloxicam (10 mg/kg/day; i.p.) for 21 days, and CRS was instigated by restraining the animals for 6 h/day during the same period. The sucrose preference test and the forced swimming test were used to explore the depression-linked anhedonia/despair, whereas the open-field test examined the animals’ locomotor activity. The current findings revealed that CRS elicited typical depression behavioral anomalies in the animals, including anhedonia, despair, and diminished locomotor activity; these findings were reinforced with Z-normalization scores. These observations were corroborated by brain histopathological changes and increased damage scores. In CRS-exposed animals, serum corticosterone spiked, and the hippocampi revealed decreased monoamine neurotransmitter levels (norepinephrine, serotonin, and dopamine). Mechanistically, neuroinflammation was evident in stressed animals, as shown by elevated hippocampal TNF-α and IL-1β cytokines. Moreover, the hippocampal COX-2/PGE2 axis was activated in the rats, confirming the escalation of neuroinflammatory events. In tandem, the pro-oxidant milieu was augmented, as seen by increased hippocampal 8-hydroxy-2′-deoxyguanosine alongside increased protein expression of the pro-oxidants NOX1 and NOX4 in the hippocampi of stressed animals. In addition, the antioxidant/cytoprotective Nrf2/HO-1 cascade was dampened, as evidenced by the lowered hippocampal protein expression of Nrf2 and HO-1 signals. Interestingly, meloxicam administration mitigated depression manifestations and brain histopathological anomalies in the rats. These beneficial effects were elicited by meloxicam’s ability to counteract the corticosterone spike and hippocampal neurotransmitter decrease while also inhibiting COX-2/NOX1/NOX4 axis and stimulating Nrf2/HO-1 antioxidant pathway. Together, the present findings prove the neuroprotective/antidepressant actions of meloxicam in CRS-induced depression by ameliorating hippocampal neuroinflammation and pro-oxidant changes, likely by modulating COX-2/NOX1/NOX4/Nrf2 axis.