Selenium (Se) has been reported to possess anti-inflammatory properties, but its bioavailability and toxicity are considerable limiting factors. The present study aimed to investigate the possible anti-inflammatory and analgesic effects of selenium nanoparticles (Nano-Se) on inflammation induced in irradiated rats. Paw volume and nociceptive threshold were measured in carrageenan-induced paw edema and hyperalgesia model. Leukocytic count, tumor necrosis factor-α (TNF-α), prostaglandin E (PGE), thiobarbituric acid reactive substances (TBAR), and total nitrate/nitrite (NOx) were estimated in the exudate collected from 6 day old air pouch model. Irradiated rats were exposed to 6 Gy gamma (γ)-irradiation. Nano-Se were administered orally in a dose of 2.55 mg/kg once before carrageenan injection in the first model and twice in the second model. The paw volume but not the nociceptive response produced by carrageenan in irradiated rats was higher than that induced in non-irradiated rats. Nano-Se were effective in reducing the paw volume in non-irradiated and irradiated rats but it did not alter the nociceptive threshold. The inflammation induced in irradiated rats increased all the estimated parameters in the exudate whereas; Nano-Se decreased their elevation in non-irradiated and irradiated rats. Nano-Se possess a potential anti-inflammatory activity on inflammation induced in irradiated rats.

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Purpose: Low dose radiation has been reported as an effective treatment for rheumatoid arthritis via multiple dose exposures. The present study was designed to increase the therapeutic efficacy of low dose radiation with the minimum exposure level in arthritic rats by concurrent administration of resveratrol (RSV) as an adjunctive therapy with anti-inflammatory properties. Materials and methods: Rats were rendered arthritic by sub-plantar injection of Freund's complete adjuvant (FCA) and exposed to low dose radiation at a total exposure level of 0.5 Gy (2 Â 0.25). During the exposure course, RSV (50 mg/kg) was orally administered once daily for two weeks. Diclofenac (3 mg/kg) was administered as a standard anti-inflammatory drug. Paw volume was measured every 4 days. After 28 days of induction, rats were sacrificed and serum was collected for estimation of tumor necrosis factor-alpha (TNF-a), interleukin-1beta (IL-1b), thiobarbituric acid reactive substances (TBARS), and total nitrate/nitrite (NO x ). Furthermore, paws were dissected for histopathological examinations and immuno-histochemical estimation of nuclear factor-kappa B p65 (NF-jB p65) expression. Results: Administration of RSV during the low dose radiation exposure course produced a significant decrease in the paw swelling and a potentiated inhibition in the serum levels of TNF-a, IL-1b, TBARs, and NO x . The dual treatment strategy alleviated the histopathological damage to a greater extent than that produced by each treatment. Moreover, a pronounced suppression of NF-jB p65 expression in the synovial tissue was observed in the combination group. The combination treatment showed a nearly similar potency to that observed in the diclofenac treated group. Conclusion: Administration of RSV augmented the modulatory activity of low dose radiation with minimum exposure level on the disease progression.

Purpose Resveratrol (RSV) is a natural polyphenolic compound that has numerous biological effects. Owing to its poor bioavailability, only trace concentrations of RSV could be found at the site of action. Therefore, the present study was aimed at developing RSV-loaded nanospanlastics to improve its oral delivery and therapeutic activity. Methods RSV-loaded nanospanlastics were prepared using the thin film hydration technique. The developed formulations were characterized via vesicular size (VS), polydispersity index (PDI), zeta potential (ZP) measurements, fourier transform infrared (FT-IR) spectroscopy analysis and transmission electron microscopy (TEM). In vitro release profile was carried out using dialysis bag diffusion technique. In vivo study was carried out using lipopolysaccharide (LPS)-induced endotoxicity model in mice to evaluate the formulations activity. Results The results revealed the successful development of RSV-loaded nanospanlastics which exhibited EE% ranging from 45 to 85%, particle sizes ranging from 260.5 to 794.3 nm; negatively charged zeta potential (≤ − 20 mV) and TEM revealed their spherical shape. An in vitro release study showed biphasic pattern with sustained release of drug up to 24 h. In vivo results showed the superiority of RSV-loaded nanospanlastics over conventional niosomes in attenuating serum levels of liver and kidney functions (aspartate transaminase (AST), alanine transaminase (ALT), and creatinine) in LPS-induced endotoxic mice. Furthermore, both of them suppressed the elevated oxidative stress and inflammatory markers (malondialdehyde (MDA), nitric oxide (NO), and interleukin-1beta (IL-1β)) estimated in the liver and kidney tissues. However, the nanospanlastics showed a prevalence effect over conventional niosomes in kidney measurements and the histopathological examinations. Conclusions These findings reveal the potential of nanospanlastics in improving the oral delivery and therapeutic efficacy of RSV.

Renal cell carcinoma (RCC) is the most fatal tumor in the urinary system. Resistance development and unmet effective responses, request new anticancer agents with better therapeutic index. Ten new imino-thiazolo-quinoxaline derivatives (5a-j) were synthesized and preliminary evaluated for downregulation of Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) activity taking sorafenib as a reference drug. Compounds 5d & 5h showed potent inhibition to VEGFR-2 activity at IC50 89.35 nM & 60.64 nM, respectively, then they both were further evaluated in-vitro against urinary bladder cancer cell line T-24 taking sorafenib as a reference drug. Compound 5h displayed nearly anticancer activity to sorafenib against T-24 cell line in all concentrations tested except at concentration 10 µM where it highly suppressed cell viability to 6.71 % compared to 15.15% of sorafenib. Compound 5h was then evaluated for its ameliorative efect against radiation induced renal tissue injury. Assessment of pro-angiogenic (VEGFR-2), pro-fibrotic (transforming growth factor-beta 1 (TGF-β1)) and apoptotic (caspase-3) markers, as well as histopathological examinations were performed on kidney of irradiated mice. Results showed ability of compound 5h to downregulate VEGFR-2 activity and its cytotoxic effect against RCC, in addition to mitigation of radiation induced renal tissue injury. Ethyl imino-thiazoloquinoxaline carboxylate derivative 5h showed a potential cytotoxic activity against RCC and could be considered a promosing alleviative candidate when employed post radiotherapy regimen. Graphical Abstract