Juliana Noguti

Oxidative stress, cancer, and sleep deprivation: is there a logical link in this association?

IntroductionSleep disorders are associated with various human pathologies and interfere with biological processes essential for health and quality of life. On the other hand, cancer is one of the most common diseases worldwide with an average of 1,500 deaths per day in the USA. Is there a factor common to both sleep disorders and cancer that serves to link these conditions?DiscussionIt is a normal process for cellular metabolism to produce reactive oxidant series (ROS). However, when the production of ROS overcomes the antioxidant capacity of the cell to eliminate these products, the resulting state is called oxidative stress. Oxidative DNA damage may participate in ROS-induced carcinogenesis. Moreover, ROS are also produced in the sleep deprivation process. The aim of this article is to review pathways and mechanisms that may point to oxidative stress as a link between sleep deprivation and cancer.

The anti-inflammatory potential of phenolic compounds in grape juice concentrate (G8000™) on 2,4,6-trinitrobenzene sulphonic acid-induced colitis.

Chronic inflammatory bowel disease is characterised by an up-regulation of the synthesis and release of a variety of pro-inflammatory mediators leading to excessive tissue injury. Flavonoids are able to inhibit enzymes and/or due to their antioxidant properties regulate the immune response. The goal of the present study was to evaluate the mechanisms of action of phenolic compounds present in grape juice on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. A total of forty-one male Wistar rats were randomised into seven groups: negative control group; TNBS non-treated induced colitis; 2% grape juice control group; 1% grape juice 24 h after TNBS colitis induction; 1% grape juice on day 7 after colitis induction; 2% grape juice 24 h after colitis induction; 2% grape juice on day 7 after colitis induction. The 1% grape juice-treated induced colitis group showed marked clinical improvement when compared with the TNBS-induced colitis group. Rats that received 1% grape juice, on day 7 after colitis induction, presented reduced intensity of macroscopic and histological scores. Statistically significant differences (P,0·05) of TNF-a and inducible NO synthase mRNA expression were detected in the groups treated with grape juice at the 1% dose after inducing experimental colitis when compared with the TNBS group. Grape juice reduced the noxious effects induced by colitis caused by TNBS, especially at the 1% dose.

Polyphenols as a chemopreventive agent in oral carcinogenesis: putative mechanisms of action using in-vitro and in-vivo test systems.

Polyphenols are present in foods and beverages, being related to sensorial qualities such as color, bitterness, and astringency, which are relevant in products such as wine, tea, and grape juice. These compounds occur naturally in forms varying from simple phenolic acids to complex polymerized tannins. Oral cancer is the most common head and neck cancer, and it often has a poor prognosis owing to local tumor invasion and frequent lymph node metastasis. Nowadays, chemoprevention is considered as a promising approach for controlling cancer as a result of specific natural products or synthetic agents able to suppress, reverse, or even prevent premalignancy before transformation into invasive cancer. The use of polyphenols as a chemopreventive agent is a suitable tool for modulation of the oral carcinogenesis process. The aim of this article is to present data generated from the use of polyphenols as a chemopreventive agent in oral carcinogenesis using in-vivo and in-vitro test systems. These results have shown that polyphenols are able to exert some chemopreventive action as a result of inducing cellular death, apoptosis, inhibition of tumor growth, and antioxidative properties. Therefore, this area warrants further investigation as a new approach that would apply not only to polyphenols but also to other phytochemicals used as promising therapeutic agents against oral human diseases, especially cancer.

Behavioral and genetic effects promoted by sleep deprivation in rats submitted to pilocarpine-induced status epilepticus

The interaction between sleep deprivation and epilepsy has been well described in electrophysiological studies, but the mechanisms underlying this association remain unclear. The present study evaluated the effects of sleep deprivation on locomotor activity and genetic damage in the brains of rats treated with saline or pilocarpine-induced status epilepticus (SE). After 50 days of pilocarpine or saline treatment, both groups were assigned randomly to total sleep deprivation (TSD) for 6 h, paradoxical sleep deprivation (PSD) for 24 h, or be kept in their home cages. Locomotor activity was assessed with the open field test followed by resection of brain for quantification of genetic damage by the single cell gel electrophoresis (comet) assay. Status epilepticus induced significant hyperactivity in the open field test and caused genetic damage in the brain. Sleep deprivation procedures (TSD and PSD) did not affect locomotor activity in epileptic or healthy rats, but resulted in significant DNA damage in brain cells. Although PSD had this effect in both vehicle and epileptic groups, TSD caused DNA damage only in epileptic rats. In conclusion, our results revealed that, despite a lack of behavioral effects of sleep deprivation, TSD and PSD induced genetic damage in rats submitted to pilocarpine-induced SE.

Correlation analysis of c-myc, p21(WAF/CIP1), p53, C-erbB-2 and COX-2 proteins in esophageal squamous cell carcinoma.

Esophageal cancer is one of the most frequently occurring malignancies and the seventh leading cause of cancer-related deaths in the world. Esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer worldwide. Our goal in this study was to detect c-myc, p21(WAF/CIP1), p53, C-erbB-2 and COX-2 immuno-expression in ESCC. Archival formalin-fixed, paraffin-embedded tissues of 18 cases of ESCC (13 biopsies and 5 surgical specimens) were studied, retrospectively, by immunohistochemistry. p53 protein was observed in 50% of the cases, while c-myc was found in 6 of 18 samples (33.33%). All samples (100%) were negative for p21(WAF/CIP1). C-erbB-2 oncoprotein and the COX-2 protein were detected in 5.5% (1/18) and 16.66% (3/18) of the cases, respectively. Taken together, our results suggest that c-myc, p53, C-erbB-2 and COX-2 proteins do not correlate with cancer stage or follow-up in ESCC as revealed by immunohistochemistry.

Genomic instability in blood cells from murine model of mucopolysaccharidosis type I

Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of alfa-iduronidase (IDUA), which leads to intralysosomal accumulation of glycosaminoglycans. Some studies have revealed that oxidative stress plays an important role in MPS I. However, the mechanisms by which these alterations occur are still not fully understood. The aim of this study was to analyze genomic instability in blood cells from murine model of MPS I by single cell gel (comet) assay and micronucleus test. The results pointed out genetic damage in blood cells as depicted by the single cell gel (comet) assay results. By contrast, no increase of micronucleated cells were found in mouse blood cells when compared to negative control. Taken together, our results suggest that IDUA deficiency induces genomic damage in blood cells. Certainly, this finding offers new insights into the mechanisms underlying the relation between IDUA deficiency and clinical manifestations that can occur in MPS I patients.

Influence of sleep deprivation and morphine on the expression of inducible nitric oxide synthase and cyclooxygenase-2 in skin of hairless mice.

Skin performs a host of primordial functions that keep the body alive. Morphine is a drug with immunosuppressant properties whose chronic use may lead to increased infection and delayed wound healing. Sleep is a fundamental biological phenomenon that promotes the integrity of several bodily functions. Sleep deprivation adversely affects several systems, particularly the immune system. The aim of this study was to perform an immunohistochemical evaluation on the expression of inducible nitric oxide synthase and cyclooxygenase-2 in skin of sleep-deprived mice and mice chronically treated with morphine. Adult hairless male mice were distributed into the following groups: Control, morphine, sleep-deprived, and morphine + SD. Morphine (10 mg/kg, subcutaneous) was injected every 12 h for 9 days. Morphine induced immunoexpression of cyclooxygenase-2 and nitric oxide synthase. Sleep deprivation did not modulate outcomes induced by morphine. Morphine, not sleep loss, induces cyclooxygenase-2 and nitric oxide synthase immunoexpression in the skin of hairless mice.

Grape juice concentrate modulates p16 expression in high fat diet-induced liver steatosis in Wistar rats

Purpose: The goal of this study was to investigate whether subchronic treatment with grape juice concentrate is able to protect the liver from high fat diet injury in rats. The effects of grape juice concentrate treatment on histopathological changes, and immunohistochemistry for p53, p16 and p21 were evaluated. Methods: Male Wistar rats (n = 18) were distributed into three groups: group 1: negative control; group 2: cholesterol at 1% (w/w) in their diet, treated during 5 weeks; and group 3: cholesterol at 1% in their chow during 5 weeks, and grape juice concentrate at 222 mg per day in their drinking-water in the last week only. Results: The results pointed out that treatment with grape juice concentrate did not show remarkable differences regarding liver tissue in the cholesterol-exposed group when compared to group 2. However, grape juice concentrate was able to modulate p16 immunoexpression when compared to high fat diet group. p53 and p21 did not show any significant statistical differences among groups. Conclusion: Taken together, our results suggest that subchronic grape juice concentrate administration was able to modulate cell cycle control by downregulation of p16 immunoexpression in high fat diet-induced liver steatosis in rats.

The influence of sleep deprivation on expression of apoptosis regulatory proteins p53, bcl-2 and bax following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.

Background: The aim of this study was to evaluate whether paradoxical sleep deprivation could affects the mechanisms and pathways essentials for cancer cells in tongue cancer induced by 4-nitroquinole 1-oxide in Wistar rats. Materials and Methods: For this purpose, the animals were distributed into 4 groups of 5 animals each treated with 50 ppm 4 nitroquinoline 1 oxide (4 NQO) solution through their drinking water for 4 and 12 weeks. The animals were submitted to paradoxical sleep deprivation (PSD) for 72 h using the modified multiple platform method, which consisted of placing 5 mice in a cage (41 × 34 × 16 cm) containing 10 circular platforms (3.5 cm in diameter) with water 1 cm below the upper surface. The investigations were conducted using immunohistochemistry of p53, Bax and Bcl-2 proteins related to apoptosis and its pathways. Statistical analysis was performed by Kruskal-Wallis non-parametric test followed by the Dunns test using SPSS software pack (version 1.0). P value < 0.05 was considered for statistic significance. Results: Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure in all groups, in 12 weeks were observed pre-neoplasic lesions. Data analysis revealed statistically significant differences (P < 0.05) in 4 weeks group for p53 and for bcl-2 and for all immunomarkers after 12 weeks of 4NQO administration. Conclusion: Our results reveal that sleep deprivation exerted alterations in proteins associated with proliferation and apoptosis in carcinogenesis.

HSP27 and HSP70 Expression in Esophageal Squamous Cell Carcinoma

Twenty-eight specimens of Esophael squamous cell carcinoma (ESCC) were obtained by surgery procedures. The tissues were fixed in formalin and embedded in paraffin. In each case, all available hematoxylin and eosin stained sections were examined and a representative block was selected. The ages of these patients ranged from 40 to 93 years, with a mean age of 60 years. Results. The histological grade of tumors was 4 well-differentiated, 19 moderately differentiated and 5 poorly differentiated. Expression of Hsp27 and Hsp70 in ESCC was demonstrated in 23 (82,14%) and 26 (92,86%) cases, respectively. Adjacent normal mucosa was positive in 11 (39,29%) samples and 9 (32,15%) samples for Hsp27 and Hsp70, respectively. No relationship between the expression of Hsp27 and Hsp70 with the clinicopathological parameters, including gender, age, surgical margin, lymph node status and tumor differentiation. The median follow-up period was 60 months. Survival analysis of patients with ESCC showed no relationship with the expression of Hsp27 and Hsp70. Conclusion. Taken together, our results demonstrate that Hsp27 and Hsp70 are expressed in ESCC tissues, but they are not good prognostic factor for patients with ESCC.