Potential antifibrotic effect of blueberry and grape polyphenol extracts in acute and subacute bleomycin-induced lung tissue injury models in mice / Potencial efecto antifibrótico de los extractos de polifenoles de arándano y uva en modelos de lesión tisular pulmonar aguda y subaguda inducida por bleomicina en ratones

SUMMARY: An experimental morphological and morphometric study of the antifibrotic function of blueberry and grape extracts was carried out on a model of lung injury in mice induced by intraperitoneal administration of bleomycin. During intraperitoneal administration of bleomycin to mice, acute and subacute damage to the pulmonary system was noted. Both patterns had the same prevalence and severity. The administration of polyphenolic extracts of blueberry and grape to mice showed a significant reduction in the severity of the acute and subacute pattern of lung injury. Blueberry and grape extracts reduce the acute phase of damage to the microvasculature, enhance phagocytic function, have an anti-inflammatory effect, reducing the degree of lymphohistiocytic infiltration and locoregional foci of residual inflammatory effects.

Se realizó un estudio experimental morfológico y morfométrico de la función antifibrótica de extractos de arándano y uva en un modelo de lesión pulmonar en ratones inducida por la administración intraperitoneal de bleomicina. Durante la administración intraperitoneal de bleomicina a ratones, se observaron daños agudos y subagudos en el sistema pulmonar. Ambos patrones tuvieron la misma prevalencia y severidad. La administración de extractos polifenólicos de arándano y uva a ratones mostró una reducción significativa en la severidad del patrón agudo y subagudo de lesión pulmonar. Los extractos de arándano y uva reducen la fase aguda del daño a la microvasculatura, mejoran la función fagocítica, tienen un efecto antiinflamatorio, reducen el grado de infiltración linfohistiocítica y los focos locorregionales de efectos inflamatorios residuales.

The Oxidative Drug Combination for Suppressing KRAS G12D Inducible Tumour Growth.

Background: Kirsten rat sarcoma (KRAS) protein is an essential contributor to the development of pancreatic ductal adenocarcinoma (PDAC). KRAS G12D and G12V mutant tumours are significant challenges in cancer therapy due to high resistance to the treatment. Objective: To determine how effective is the ATO/D-VC combination in suppression of PDAC the mouse transgenic model. This study investigated the antitumour effect of a novel combination of arsenic trioxide (ATO) and D-ascorbic acid isomer (D-VC). Such a combination can be used to treat KRAS mutant cancer by inducing catastrophic oxidative stress. Methods: In this study, we examined the effectiveness of ATO and D-VC on xenograft models-AK192 cells transplanted into mice. Previously, it has been shown that a high concentration of Vitamin C (VC) selectively can kill the cells expressing KRAS. Results: The results of this study demonstrated that the combination of VC with a low dose of the oxidizing drug ATO led to the enhancement of the therapeutic effect. These findings suggest that the combined treatment using ATO and D-VC is a promising approach to overcome the limitation of drug selectivity and efficacy.

Osteoprotective properties of RNA-containing drug osteochondrin S on the model of insufficiency of sex hormones in rats / Propiedades osteoprotectoras del fármaco que contiene ARN de osteocondrina S sobre un modelo de insuficiencia de hormonas sexuales en ratas

SUMMARY: The aim of the study was to evaluate the osteoprotective properties of RNA-containing drug Osteochondrin S on rats with experimental model of osteoporosis. Osteochondrin S contains yeast RNA and RNA of connective tissue of cattle. In order to model osteoporosis in rats bilateral ovariectomy was used. Rats were divided into 3 groups: 1 - ovariectomized rats receiving Osteochondrin S; 2 - ovariectomized rats receiving saline; 3 - sham-ovariectomized rats. Rats in group 1 received Osteochondrin S, Group 2 - physiological saline three times a week for 12 weeks. Based on morphological data and on the results of densitometry, Osteochondrin S prevents a decrease in bone density, i.e. exhibits osteoprotective properties. Under the condition of lack of sex hormones in rats Osteochondrin S reduces reactive oxygen species in blood plasma and limits the degree of decrease in antioxidant capacity of blood plasma.

RESUMEN: El objetivo de este estudio fue evaluar las propiedades osteoprotectoras del fármaco que contiene ARN Osteocondrina S en ratas, como modelo experimental de osteoporosis. La Osteocondrina S contiene ARN de levadura y ARN de tejido conectivo de bovinos. Para modelar la osteoporosis en ratas se utilizó ovariectomía bilateral. Las ratas se dividieron en 3 grupos: grupo 1, ratas ovariectomizadas que recibieron Osteocondrin S; grupo 2, ratas ovariectomizadas recibieron solución salina; grupo 3 - ratas ovariectomizadas simuladas. Las ratas del grupo 1 recibieron Osteocondrina S, el grupo 2 solución de suero fisiológico tres veces por semana durante 12 semanas. En base a los datos morfológicos y los resultados de la densitometría, Osteocondrina S evita una disminución de la densidad ósea, es decir, exhibe propiedades osteoprotectoras. Ante la falta de hormonas sexuales en ratas, Osteocondrina S reduce las especies reactivas de oxígeno en el plasma sanguíneo y limita el grado de disminución de la capacidad antioxidante del plasma sanguíneo.

Red blood cell ghosts as promising drug carriers to target wound infections.

Autologous red blood cell ghosts (RBC ghosts) can carry cytokines to the sites of inflammation. The targeting moiety of the RBC ghosts is associated with the nature of purulent inflammation, where the erythrocytes are phagocyted and encapsulated drugs are released. In the present study we have investigated the healing potential of RBC ghosts loaded with cytokine IL-1ß and antibiotic. Additionally, the pharmacokinetic properties of RBC ghosts loaded with IL-1ß were studied. 35 Male Wistar rats (250-300g) were used in the pharmacokinetic study and in a wound infection model where a suspension of Staphylococcus aureus was placed into a surgical cut of the skin and subcutaneous tissue in the femoral region. In order to monitor progression of the wound repair processes, wound swabs or aspiration biopsies were taken for analyses on the 1st-6th days. Wound repair dynamics assessment was based on suppression of S. aureus growth, signs of pain, time of disappearance of pus and infiltration around the wound. Visual observations, as well as microbiological and cytological analysis of wound exudates demonstrated a significant acceleration of healing processes in a group of animals treated with a local injection of IL-1ß and ceftriaxone encapsulated into RBC ghosts when compared to the animals treated either with a local or IM injection of free drugs. For the pharmacokinetic study, single IV injections of either free or encapsulated IL-1ß were made and the concentration of IL-1ß in serum samples and tissue homogenates were determined. Encapsulation in RBC ghosts improved pharmacokinetic profiles of IL-1ß by increasing the half-life, reducing its clearance, and increasing the deposition of the drug in the liver, spleen and lungs. These data suggest that RBC ghosts are effective drug carriers for targeted delivery of cytokines to the sites of inflammation, and have a potential for improving the treatment outcomes of purulent diseases.