Apigenin and Exposure to Low Dose Gamma Radiation Ameliorate Acetic Acid-Induced Ulcerative Colitis in Rats.

Ulcerative colitis (UC) is an inflammatory bowel disease involving chronic and recurring colon inflammation. Current management protocols are limited by adverse effects or short-term symptomatic relief. We aimed to investigate the possible therapeutic prospect of low dose gamma (γ) irradiation or apigenin treatment in acetic acid-induced UC in rats. Induction of UC was carried out by installation of acetic acid intra-rectally. One hour post-induction, rats received a sole dose of γ-radiation (0.5 Gray) or were treated with apigenin (3 mg/kg/day, peroral) for 7 successive days. Antioxidant and anti-inflammatory effects of both agents were assessed via determination of colon malondialdehyde (MDA), reduced glutathione (GSH), total nitrate/nitrite (NOx), mucosal addressin cell adhesion molecule-1 (MAdCAM-1), and interleukin-1beta (IL-1ß) contents as well as myeloperoxidase (MPO) activity. Body weight (BW), colon weight/length (W/L) ratio, disease activity index (DAI), and histopathological changes were evaluated. Gamma irradiation and apigenin significantly ameliorated the acetic acid-induced biochemical and histopathological changes. Both therapeutic approaches significantly restored colon contents of the investigated biomarkers. They modulated BW, colon W/L ratio and DAI. This study proposes low dose γ-irradiation as a new therapeutic candidate for the management of UC. We also concluded that apigenin exhibited therapeutic benefits in UC management.

Tailoring of chitosan/diacrylated pluronic system as a versatile nanoplatform for the amelioration of radiation-induced cognitive dysfunction.

Rutin (RUT) is a biologically active flavonoid that is reported to modulate radiation-induced brain dysfunctions. However, RUT's poor water solubility and low brain bioavailability limit its clinical use. To increase its brain bioavailability, RUT was loaded onto nanoplatforms based on chitosan/diacrylated pluronic (CS/DA-PLUR) nanogels synthesized by gamma radiation. The optimized formulation was investigated as a carrier system for RUT. Based on pilot experiments' results, the cranial radiation (CR) dose that induced cognitive dysfunction was selected. In the main experiment, rats were pre-treated orally with either free RUT or RUT-CS/DA-PLUR. Rats' cognitive and motor functions were assessed; 24 h later, rats were sacrificed, and the whole brain was separated for histopathological examination and biochemical estimation of brain content of acetylcholine esterase (AChE), neurotransmitters, oxidative stress markers, and interleukin-1ß. CR produced prominent impairment in spatial and non-spatial learning memory, motor coordination, and muscular strength. Moreover, histopathological and biochemical alterations in brain contents of neurotransmitters, oxidative stress, and interleukin-1ß were induced by CR. Conversely, RUT-CS/DA-PLUR, but not free RUT, successfully guarded against all the detrimental effects induced by CR. Based on the current findings, loading of RUT enhanced its bioavailability and therapeutic effectiveness by restoring the cognitive functions impaired by CR.

Platelet-rich plasma-induced feedback inhibition of activin A/follistatin signaling: A mechanism for tumor-low risk skin rejuvenation in irradiated rats.

BACKGROUND: Platelet-rich plasma (PRP) is a source of natural growth factors and is emerging as a treatment modality to mitigate radiotherapy- induced adverse effects. Activin A (ACTA) is a member of the transforming growth factor-ß (TGF-ß) superfamily, which has been shown to modulate the inflammatory response and macrophages polarization between different phenotypes. The aim of this study is to determine the value of PRP in preventing radiation-induced malignancies in light of the cross-talk between PRP and activin A type II receptors (ActR-IIA)/follistatin (FST) signaling pathways where the inflammatory responses at 2 different time points were evaluated. MATERIAL AND METHODS: Male albino rats were exposed to radiation and given PRP over the course of 6 days. Rats were sacrificed on day 7 or day 28 post radiation. RESULTS: Quantitative real-time reverse transcriptase polymerase chain reaction (QRT-PCR) and western-blot showed that after 7 days of administrating of PRP, ActR-IIA/FST signaling was markedly induced and was associated with the expressions of inflammatory, natural killer and M1 macrophages markers, TNF-α, IL-1ß, IFN-γ and IL-12. By contrast, on day 28 of PRP administration, ActR-IIA/FST signaling and the expressions of proinflammatory cytokines were downregulated in parallel with inducing M2 macrophages phenotype as indicated by arginase-1, IL-10 and dectin-1. CONCLUSION: The suppression of inflammation and induction of M2 macrophages phenotype in response to PRP administration were found significantly linked to ActR-IIA/FST signaling downregulation. Furthermore, the specific M2 macrophage subtype was found to express dectin-1 receptors which have high affinity for tumor cells thereby is expected to reduce the potential for developing tumors after radiotherapy.

Anti-ulcerogenic effect of aqueous propolis extract and the influence of radiation exposure.

PURPOSE: To study the effect of aqueous propolis extract (AEP) against indomethacin (Indo)-induced gastric ulcers in irradiated and non-irradiated rats. MATERIALS AND METHODS: Animals were irradiated at different radiation dose levels before the induction of ulcers. AEP was injected orally 1 hour before induction of gastric ulcers and the effects compared with those of lansoprazole (Lanso), which was used as a reference anti-ulcerogenic drug. RESULTS: Pretreatment of rats, either irradiated or non-irradiated, with AEP effectively protected against Indo-induced gastric ulceration. This was associated with a reduction in acid output and peptic activity and an increase in the secretion of mucin. The mucosal prostaglandin E(2) (PGE(2)) level was also increased. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1ß) were suppressed to the same extent after treatment. Both propolis and Lanso were effective in reducing the number of gastric lesions as well as the plasma level of malondialdehyde (MDA). CONCLUSIONS: These findings indicate that the gastroprotective effect of AEP could be of value in the management of excessive gastric damage induced by radiation exposure.