Authors:Gy Kovács, Z. Petrovszki, J. Mallareddy, G. Tóth, Gy Benedek and Gyöngyi Horváth
This study reports on the in vivo effects of four endomorphin-2 (EM-2) derivatives (EMD1-4) containing unnatural amino acids, i.e. 2-aminocyclohexanecarboxylic acid (Achc2), para-fluorophenylalanine (pFPhe4), β-methylphenylalanine (βMePhe4) and/or 2′,6′-dimethyltyrosine (Dmt1). After induction of osteoarthritis by monosodium iodoacetate into the ankle joint of male Wistar rats, a chronic intrathecal catheter was inserted for spinal drug delivery. The mechanical threshold was assessed by a dynamic aesthesiometer. Intrathecal injection of the original EM-2 and the ligands (0.3–10 μg) caused dose-dependent antiallodynic effects. The comparison of the different substances revealed that EMD3 and EMD4 showed more prolonged antinociception than EM-2, and the effects of the highest dose of EMD4 were comparable to morphine, while EMD3 caused paralysis at this dose. The potency of the different ligands did not differ from EM-2. The results show that the derivatives of EM-2 have similar in vivo potency to the original ligand, but their effects were more prolonged suggesting that these structural modifications may play a role in the development of novel endomorphin analogues with increased therapeutic potential.
Authors:V. Virág, T. Varjas, Z. Gyöngyi, G. Somlyai, I. Ember and E. Nádasi
Despite many different trials, no effective dietotherapy exists for curing enormous weight loss caused by malignant diseases yet. The present study was aimed at determining in an animal model, weather some natural products might be included in the dietotherapy of cancerous patients with cachexia. Tumour was transplanted into Fischer 344 rats drinking either seabuckthorn extract, green tea, deuterium depleted water, trace elements preparation, fruits’ extract or multivitamin solution. Weight loss, tumour growth and expression of Ha-ras gene were determined. All the investigated natural products have significantly decreased tumour growth, and trace elements preparation has significantly decreased weight loss. Green tea, seabuckthorn extract and deuterium depleted water have notably diminished Ha-ras gene expression. Our results suggest that these natural products may be useful in inhibiting tumour growth, and some of them may be applied in the dietotherapy of cancer-related weight loss.
Authors:B Raposa, R Pónusz, G Gerencsér, F Budán, Z Gyöngyi, A Tibold, D Hegyi, I Kiss, Á Koller and T Varjas
It has been reported that some of the food additives may cause sensitization, inflammation of tissues, and potentially risk factors in the development of several chronic diseases. Thus, we hypothesized that expressions of common inflammatory molecules – known to be involved in the development of various inflammatory conditions and cancers – are affected by these food additives. We investigated the effects of commonly used food preservatives and artificial food colorants based on the expressions of NFκB, GADD45α, and MAPK8 (JNK1) from the tissues of liver. RNA was isolated based on Trizol protocol and the activation levels were compared between the treated and the control groups. Tartrazine alone could elicit effects on the expressions of NFκB (p = 0.013) and MAPK8 (p = 0.022). Azorubine also resulted in apoptosis according to MAPK8 expression (p = 0.009). Preservatives were anti-apoptotic in high dose. Sodium benzoate (from low to high doses) dose-dependently silenced MAPK8 expression (p = 0.004 to p = 0.002). Addition of the two preservatives together elicited significantly greater expression of MAPK8 at half-fold dose (p = 0.002) and at fivefold dose (p = 0.008). This study suggests that some of the food preservatives and colorants can contribute to the activation of inflammatory pathways.