Therapeutic effects of vitamin D and IL-22 on methotrexate-induced mucositis in mice.

Mucositis is a common side effect of cancer therapies and transplant conditioning regimens. Management of mucositis involves multiple approaches from oral hygiene, anti-inflammatory, anti-apoptotic, cytoprotective, and antioxidant agents, to cryo-therapy, physical therapy, and growth factors. There is room for novel, affordable treatment options, or improvement of currently available therapies. Vitamin D has been shown to regulate mucosa-resident cell populations such as Th17 or innate lymphoid cells and critical mucosal cytokine IL-22; however, their therapeutic potential has not been put to test in preclinical mouse models. In this study, we aimed to test the therapeutic potential of vitamin D injections and IL-22 overexpression in a murine model of chemotherapy-induced mucositis. Balb/c mice were given daily intraperitoneal injections of vitamin D. Mucositis was induced by methotrexate. Another group received IL-22 plasmid via hydrodynamic gene delivery. Weight loss and intestinal histopathology, intestinal levels of cytokines IL-22, IL-17A, GM-CSF, IL-23, IFN-γ, TNF-α, and IL-10, and number of intestinal lamina propria B cell, neutrophil, and total innate lymphoid cells were quantified. Daily vitamin D injections ameliorated intestinal inflammation and elevated intestinal IL-22 levels compared with control groups. Temporal overexpression of IL-22 by hydrodynamic gene delivery slightly increased intestinal IL-22 but failed to confer significant protection from mucositis. To our knowledge, this is the first experimental demonstration in an animal model of mucositis of therapeutic use of vitamin D and IL-22 supplementation and our results with vitamin D suggest it may have merit in further trials in human mucositis patients.

Hepatoprotective effects of capping protein gelsolin against hyperoxia-induced hepatotoxicity, oxidative stress and DNA damage in neonatal rats.

Tissues and organs get exposed to high oxygen (O2) supply in hyperoxia conditions. The goal of this research was to investigate the protective effect of actin binding protein gelsolin on hyperoxia-induced hepatotoxicity through histopathology and measurement of oxidative stress parameters and DNA damage in a neonatal Wistar albino rats. The pups were randomly separated to four equal groups such as: normoxia control group (NC), normoxia plus gelsolin group (NG, 10 ng/kg bw/day gelsolin), hyperoxia (≥85% O2) group (HC), hyperoxia plus gelsolin group (HG, ≥85% O2; 10 ng/kg bw/day gelsolin). Histopathological changes of pups in hyperoxia condition were revealed in the form of severe leukocyte infiltration, vascular congestion, necrosis, vacuolar degeneration, binucleated hepatocytes and hemorrhage in the liver tissue. SOD, CAT, GPx and GST activities decreased and MDA level increased in the hyperoxia-induced group in liver tissue (P < 0.05). Tail DNA%, tail length and moment indicating DNA damage statistically increased in hyperoxia treatment groups when compared to controls. Treatment of rats with hyperoxia plus gelsolin prevented hyperoxia-induced changes in tissue structure, antioxidant enzyme activities and MDA level, mean tail DNA% and length. Based on these findings, gelsolin restored these changing to near normal levels but it does not protect completely in the hyperoxia conditions.

Protective effect of vitamin D against hyperoxia-induced lung injury in newborn rats.

INTRODUCTION: Preterm infants have risks of developing vitamin D deficiency. Thus we aimed to investigate the effect of vitamin D on hyperoxia-induced lung injury in newborn rats. METHODS: Full term rat pups were included in the study 12-24 hr after delivery. The pups were randomly divided into eight groups as follows: normoxia control group (NC), normoxia plus vitamin D group (ND1, 1 ng/gr/day vitamin D), normoxia plus vitamin D group (ND2, 3 ng/gr/day vitamin D), normoxia plus vitamin D group (ND3, 5 ng/gr/day vitamin D), hyperoxia control group (HC), hyperoxia plus vitamin D group (HD1, 1 ng/gr/day vitamin D), hyperoxia plus Vitamin D group (HD2, 3 ng/gr/day vitamin D), hyperoxia plus vitamin D group (HD3, 5 ng/gr/day vitamin D). The histopathological effects of vitamin D were assessed by alveolar surface area (with mean linear intercept (MLI) method), apoptosis index and proliferating cell nuclear antigen (PCNA) index. RESULTS: MLI values were significantly lower among three groups (HD1: 83.93 ± 1.95 µm, HD2: 81.76 ± 1.68 µm, and HD3: 82.33 ± 1.87 µm) when compared with HC group (92.98 ± 2.09 µm) (P = 0.001, P = 0.0004, P = 0.002, respectively). Apoptotic cell index were significantly lower among three treatment groups (HD1: 1.455 ± 0.153, HD2: 0.575 ± 0.079, and HD3: 0.700 ± 0.105) when compared with HC group (2.500 ± 0.263) (P = 0.001, P = 0.001, P = 0.001, respectively). Although PCNA positive cell index did not change in HD1 group (0.132 ± 0.008) (P > 0.05), there were significant increases in HD2 (0.277 ± 0.026) and HD3 (0.266 ± 0.018) group when compared with HC group (0.142 ± 0.010) (HD2 P = 0.001, HD3 P = 0.001). CONCLUSION: Vitamin D seems to protect hyperoxia-induced lung injury in newborn rats. Pediatr Pulmonol. 2017;52:69-76. © 2016 Wiley Periodicals, Inc.

Effects of Cornus mas L. and Morus rubra L. extracts on penicillin-induced epileptiform activity: an electrophysiological and biochemical study.

Traditionally, Morus rubra L. (Moraceae) (red mulberry) and Cornus mas L. (Cornacea) (cornelian cherry) fruits are eaten fresh and are also used in marmalades, juices, jam, natural dyes in Turkey and are believed to have beneficial effects in case of multiple health issues such as antipyretic, diarrhea and intestinal parasites. However, the effects of M. rubra and C. mas on epilepsy has not been known. This study evaluates the effects of M. rubra and C. mas extracts on penicillin-induced epileptiform activity. Sixty Wistar rats randomly divided into ten groups (n=6): control, sham, penicillin, penicillin+M. rubra extract (2.5, 5, 10, 20 mg/kg) and penicillin+C. mas extract (2.5, 5, 10 mg/kg). Epileptiform activity was induced by using penicillin (500 IU, i.c.) and electrocorticogram records (150 min) were obtained. Also, biochemical analysis in blood samples were evaluated. According to the electrocorticogram analysis, the effective dose was detected as 10 mg/kg for both C. mas and M. rubra. This dose decreased the spike frequencies of convulsions while amplitude wasn't changed by both substances. In erythrocyte studies, there were significant differences regarding nitric oxide in the control, sham and penicillin groups. There were significant differences regarding malondialdehyde in all groups. In the plasma, there were significant differences among groups regarding xanthine oxidase in the penicillin­C. mas and penicillin­M. rubra groups. There were differences regarding malondialdehyde in the penicillin-C. mas and M. rubra-C. mas groups. Both extracts reduced the frequency of epileptiform activity. After administration of the extracts malondialdehyde levels decreased also in both erythrocytes and plasma.