N-methyl-D-aspartate receptors and thymoquinone induce apoptosis and alteration in mitochondria in colorectal cancer cells.

Colon cancer is on the rise in both men and women. In addition to traditional treatment methods, herbal treatments from complementary and alternative medicine are actively followed. Naturally derived from plants, thymoquinone (TQ) has drawn a lot of attention in the field of cancer treatment. MK-801, an N-methyl-D-aspartate agonist, is used to improve memory and plasticity, but it has also lately been explored as a potential cancer treatment. This study aimed to determine the roles of N-Methyl-D-Aspartate agonists and Thymoquinone on mitochondria and apoptosis. HT-29 cells were treated with different TQ and MK-801 concentrations. We analyzed cell viability, apoptosis, and alteration of mitochondria. Cell viability significantly decreased depending on doses of TQ and MK-801. Apoptosis and mitochondrial dysfunctions induced by low and high doses of TQ and MK-801. Our study emphasizes the need for further safety evaluation of MK-801 due to the potential toxicity risk of TQ and MK-801. Optimal and toxic doses of TQ and MK-801 were determined for the treatment of colon cancer. It should be considered as a possibility that colon cancer can be treated with TQ and MK-801.

Therapeutic and prophylactic role of vitamin D and curcumin in acetic acid-induced acute ulcerative colitis model.

Ulcerative Colitis (UC) is a disease that negatively affects quality of life and is associated with sustained oxidative stress, inflammation and intestinal permeability. Vitamin D and Curcumin; It has pharmacological properties beneficial to health, including antioxidant and anti-inflammatory properties. Our study investigates the role of Vitamin D and Curcumin in acetic acid-induced acute colitis model. To investigate the effect of Vitamin D and Curcumin, Wistar-albino rats were given 0.4 mcg/kg Vitamin D (Post-Vit D, Pre-Vit D) and 200 mg/kg Curcumin (Post-Cur, Pre-Cur) for 7 days and acetic acid was injected into all rats except the control group. Our results; colon tissue TNF-α, IL-1ß, IL-6, IFN-γ and MPO levels were found significantly higher and Occludin levels were found significantly lower in the colitis group compared to the control group (p < 0.05). TNF-α and IFN-γ levels decreased and Occludin levels increased in colon tissue of Post-Vit D group compared to colitis group (p < 0.05). IL-1ß, IL-6 and IFN-γ levels were decreased in colon tissue of Post-Cur and Pre-Cur groups (p < 0.05). MPO levels in colon tissue decreased in all treatment groups (p < 0.05). Vitamin D and Curcumin treatment significantly reduced inflammation and restored the normal histoarchitecture of the colon. From the present study findings, we can conclude that Vitamin D and Curcumin protect the colon from acetic acid toxicity with their antioxidant and anti-inflammatory potential.Brief synopsis: In this study; distal colon, distal ileum, jejunum and serum physiopathology in colitis induced by acetic acid and intestinal permeability were investigated. The roles of vitamin D and curcumin in this process were evaluated.

Protective effects of Ficus carica seed oil on ischemia and reperfusion injury in a rat model of acute mesenteric ischemia.

BACKGROUND: The increase in free oxygen radicals and proinflammatory cytokines in the ischemia-reperfusion injury caused by acute mesenteric ischemia are the key responsibilities of intestinal histopathological alterations. It has been reported that Ficus carica and its various parts contain antioxidant and anti-inflammatory compounds recently. Thus, in the present study, we aimed to investigate how Ficus carica seed oil affects intestinal ischemia-reperfusion injury in a rat model. METHODS: In this study, 50 male Wistar albino rats were randomly divided into five equal groups. Negative control (NC), sham-operated (Sham), ischemia and reperfusion (IR), 3 ml/kg/day Ficus carica seed oil (FC3), 6 ml/kg/day Ficus carica seed oil (FC6). IR, FC3 and FC6 groups underwent ischemia and reperfusion procedure for 45+120 min. Only abdominal midline laparotomy was performed in the Sham group for 165 minutes. RESULTS: Tissue levels of TNFα and IL-1ß, which were proinflammatory cytokines, were significantly reduced in the FC6 group than the IR group (p<0.05). In FC3 and FC6 groups, the tissue MPO and MDA enzyme levels were significantly lower than the IR group, but there was a significantly greater decrease in the FC6 group than the FC3 group (p<0.05). SOD and CAT enzymes and reduced glutathione levels of FC3 and FC6 groups were significantly lower than IR group (p<0.05); however, there was no statistically significant difference between the FC3 and FC6 groups. FC3 and FC6 groups were histopathologically graded statistically lower than the IR group, and the FC6 group showed a significant decrease than the FC3 group (p<0.05). CONCLUSION: Oral administration of fig seed oil may reverse biochemical and histopathological findings resulting from ischemia-reperfusion injury in an experimental model of acute mesenteric ischemia in rats, probably because of its antioxidant and anti-inflammatory compounds.

Long-term protective effects of the combination of intermittent reperfusion and hypothermia on reperfusion injury in an experimental testicular torsion model.

INTRODUCTION: There are many significantfactors in testicular injury which determine the prognosis in testicular torsion. Reperfusion injury following detorsion also has a significant effect on testicular injury.This study was planned considering that with the implementation of intermittent reperfusion and hypothermia, reperfusion injury can be reduced, and such an application might have a positive effect on testicular tissue in the long term. MATERIALS AND METHODS: Forty adult male rats were divided into five groups as follows: Sham(Sh)(n = 8), Torsion(T)(n = 8), Intermittent reperfusion(IR)(n = 8), Hypothermia(H)(n = 8), and Intermittent reperfusion+hypothermia(IR+H)(n = 8). Except forGroup Sh, the left testicle was taken out of the scrotum in all groups, rotated three times counterclockwise, fixed back in the scrotum, and left for four hours.After four hours, and just before reperfusion, the testicle's detorsion was performed while holding the vascular structures in the proximal part of the torsed segment with an atraumatic vessel clamp, and thus, not allowing reperfusion in Groups T, IR, H, and IR+H. In Group T, the clamp was released immediately. In Group H, an ice-bag cooling was performed around the testis, and the clamp was released when the tissue temperature was reached and kept constant at 4 °C. In Group IR, the clamp was released, allowing reperfusion of five seconds, followed by reclamping, providing an ischemic status for ten seconds; this procedure was repeated ten times. In Group H+IR,an ice-bag cooling was performed around the testis, and the clamp was released when the tissue temperature was reached and kept constant at 4 °C. Then, reperfusion was applied for 5 s, followed by 10 s ischemia with reclamping. This procedure was repeated ten times.Tissue blood flow was provided for60 days of reperfusion in all groups. After 60 days, both testicles were excised under anesthesia in all living rats, and samples ofthe left testicle werereserved for biochemical and pathological examinations. At the end of the procedure, all animals were sacrificed by a high dose of anesthesia. RESULTS: It was biochemically and histopathologically determined that the tissues were preserved in the experimental groups compared to Group T, which was statistically significant (p < 0.05).However, no experimental group's superiority over each other was determined both biochemically and histopathologically (p > 0.05). CONCLUSION: Our long-term experimental study revealed that all methods were protective in testicular torsion. The authors believe that these methods can be applied in clinical practice because of their ease of application and no additional cost. On the other hand, the results of our study should further be supported by other experimental studies.

Comparison of the effects of intermittent reperfusion and hypothermia in preventing testicular ischemia-reperfusion injury in the testicular torsion model in rats.

INTRODUCTION: Reperfusion injury after detorsion in testicular torsion is a clinical problem. This study was planned to investigate the protective effect of intermittent reperfusion in hypothermia-applied testicles. MATERIALS AND METHODS: A total of 40 adult male rats were used, and 5 groups were created: sham (Sh; n = 8), torsion (T; torsion-detorsion) (n = 8), intermittent reperfusion (IR; n = 8), hypothermia (H; n = 8), and intermittent reperfusion+hypothermia (H+IR; n = 8). The left testicle was removed in all groups except in the Sh group, and it was rotated 3 times counterclockwise, fixed in the scrotum, and left for 4 h. After 4 h, the testicle was detorsioned in the groups T, IR, H, and H+IR. During detorsion, an atraumatic vessel clamp was applied in the proximal part of the vascular structures to prevent any reperfusion of the testicle. The clamp was opened immediately in the group T. In the group IR, the clamp was opened, a reperfusion of 5 s was applied; then, the clamp was closed again, and ischemia was created for 10 s; this procedure was repeated 10 times. In the group H, an ice bag cooling was performed around the testis. The tissue temperature was kept constant at 4 °C using a digital thermometer control. The testicle was cooled using an ice bag in the group H+IR; the same procedure was applied to the IR group. In all groups, reperfusion was performed for 1 h at the end of these procedures. The left testicle was removed from all rats; a portion of each testicle was separated for biochemistry testing, and some was separated for histopathological evaluation. At the end of the procedure, intracardiac blood was taken to examine oxidative stress parameters. At the end of the procedure, all animals were sacrificed after administration of a high dose of anesthesia. RESULTS: The authors observed that the tissue was preserved in the experimental groups and this was statistically significant (p<0.05). It was detected that the tissues were also histopathologically and significantly preserved in the groups IR, H, and H+IR. However, both biochemically and histopathologically, there was no superiority of hypothermia, intermittent reperfusion, or combined application (p>0.05). DISCUSSION: Both hypothermia and intermittent reperfusion alone protect tissue from IR damage. But no studies have been found in which these applications were used together. And as a result of this work, the combination of both methods did not show superiority over the effect they showed when they were used separately. The authors think that these methods can be applied clinically because of their ease of application and no additional costs; however, it should be supported by other studies.

Effect of experimentally induced hypothyroidism during gestation period on activity dependent neurotrophic factor (ADNF) in newborn rat brain tissue.

Purpose The aim of the study was to evaluate the effects of prenatal hypothyroidism on neonatal rats by the way of activity-dependent neuroprotective factor (ADNF) expression. Methods Twenty-one Wistar albino neonatal rats were divided into two subgroups; a control group and neonatal rats with experimental maternal hypothyroidism. Hypothyroidism was induced by using propylthiouracil (PTU). Neonatal rats obtained PTU from breast milk continuously for 1 week after birth. The rats from the control group were fed only normal feed and water. After birth, body weight and blood thyroid hormone levels were tested. Glial fibrillary acidic protein (GFAP), Slug, Numb, Notch-1 and ADNF antibodies were used for immunohistochemical analysis. Real-time polymerase chain reaction (RT-PCR) and Western blotting analyses were used to evaluate ADNF gene expression levels from 1-week-old rat's brain. Results There was no difference between the two groups for birth weights. The thyroxine (T4) level from the experimental group was <0.4 ng/mL, and it was 0.8 ng/mL for the control group. It was shown that, the results from the experimental group samples had significantly lower ADNF mRNA levels than control group (p < 0.05). The increase from GFAP and Numb expression and decrease from Slug expression were shown in the experimental group. Local differences were identified for ADNF and a decrease was shown in both sides of brain. There was no difference for Notch-1 expression for both groups. Conclusion In this study, decreasing ADNF expression might contribute to developing neurological problems in congenital hypothyroidism.