Methotrexate-loaded biodegradable nanoparticles exert anti-arthritic effect by downregulating pro-inflammatory cytokines in Freund's complete adjuvant-induced arthritic rats.

Methotrexate (MTX), the first-line drug for the treatment of rheumatoid arthritis (RA), can cause considerable toxicity, which limits effective dosage regimens. Moreover, it has rapid clearance, which leads to poor patient compliance. To mitigate such challenges, this study aimed to validate the use of MTX-loaded chitosan nanoparticles (NPs) in treating Freund's complete adjuvant (FCA) arthritis in rats. Healthy Wistar rats (n = 30) were divided into five groups. The first group served as healthy control, while the second group served as arthritic control. Group 3 was administered methotrexate, while groups 4 and 5 were MTX-loaded NP-treated groups. NPs were prepared by solvent evaporation method and characterized by zeta size, potential, polydispersity index (PDI), and Fourier-transform infrared spectroscopy. NPs were 190 nm in size, and PDI was 0.25, confirming the uniform distribution of NPs. A significant increase in paw thickness was noted up to the 21st day of the study, which was reversed by a high dose of MTX-loaded NPs. MTX NPs significantly reduced the level of pro-inflammatory markers, including TNF-α and IL-6, along with improving control of oxidative stress biomarkers. The findings of biochemical, haematological, radiological, and histopathological investigations further confirmed amelioration of necrosis and cellular infiltration. It can be concluded that MTX-loaded chitosan NPs are promising candidates for treating FCA-induced arthritis in a rat model.

Biotransformation and toxicity evaluation of functionalized manganese doped iron oxide nanoparticles.

Safe inorganic nanomaterials are tremendously used for diagnosis and therapies. However, essential processing in the microbiological environment changed the physical properties and in situ degradability, which is evaluated meticulously. In this research article, bare, Polyethylene glycol, and citrate coated manganese doped iron oxide nanoparticles are synthesized through the coprecipitation route. Structural, magnetic, optical, and morphological analyses are performed through different characterization tools. X-ray diffraction confirmed the formation of single-phase FeMnO3 with a crystallite size of 48.91 nm. Vibrating sample magnetometer analysis confirmed the formation of soft ferromagnetic behavior of bare and coated nanoparticles (NPs). Scanning electron microscopy and transmission electron microscopy confirmed the formation of spherical shaped nanoparticles. Single-dose in vivo acute toxicity testing is performed through the intraperitoneal route of administration on groups of healthy albino rats. Elevated enzyme levels of kidney and liver are observed at day 1 but a transient decrease is observed at later stages. Through optical follow-up, degradation effects are studied by adding prepared NPs in lysosomal like medium. Finally, metabolization of degraded products based on manganese/iron ions is studied by adding apoferritin into a lysosome like solution. These studies showed partial storage of manganese ions from NPs, while no substantial transfer is observed in the case of manganese salt.

Induction of LRF-1/ATF3 by vasopressin in hepatocytes: role of MAP kinases.

BACKGROUND/AIMS: Liver regeneration factor 1 (LRF-1/ATF3) is an early response gene which is rapidly induced upon partial hepatectomy in rats, and by growth factors and G protein-coupled receptor (GPCR) agonists in cultured rat hepatocytes. The aim of the present study was to examine the mechanisms involved in induction of LRF-1/ATF3 by the GPCR agonist vasopressin. METHODS: Primary cultures of rat hepatocytes were treated with vasopressin, TPA, and the Ca2+-elevating agents thapsigargin and A23187. LRF-1/ATF3 mRNA and protein were measured by Northern blot analysis or RT-PCR and immunoblotting. Signalling pathways were examined by immunoblots and kinase assays. RESULTS: While elevation of intracellular calcium induced LRF-1/ATF3 expression, treatment with TPA did not. Inhibition of phospholipase C, protein kinase C, or pretreatment with calcium chelators did not affect vasopressin-induced expression of LRF-1/ATF3. Inhibition of each of the MAP kinases ERK1/2, JNK or p38 did not affect vasopressin-induced LRF-1/ATF3 expression. Combined inhibition of JNK and p38, and of ERK1/2 and either JNK or p38 suppressed vasopressin-induced expression of LRF-1/ATF3. CONCLUSION: Vasopressin induces LRF-1/ATF3 expression by mechanisms that differ from those activated by Ca2+-elevating agents. The results suggest that partly redundant, complex MAP kinase networks are involved in induction of LRF-1/ATF3 by vasopressin in hepatocytes.