Assessment of genotoxicity of glass ionomer cements: a systematic review.

To evaluate, through a systematic review, the assessment of genotoxicity of glass ionomer cements in vitro and in vivo. A systematic review was performed with the problem, intervention, control, and outcomes (PICOS) strategy, aiming to answer the following question: "Can glass ionomer cements induce genetic damage in vitro and in vivo?" A systematic search was performed in the following electronic databases: PubMed (including MedLine), Web of Science, and Scopus. The quality of included studies was assessed using the Effective Public Health Practice Project (EPHPP). After the authors performed the review of all articles, a total of 13 manuscripts met all the inclusion criteria in the systematic review. Following the parameters of the EPHPP, eight articles were classified as strong or moderate quality. The other ones (five studies) were weak. Taken together our results demonstrated that, six studies reported genotoxicity of the modified glass ionomer cements tested and two studies concluded that the effect of genotoxicity was time dependent.

Parental High-Fat High-Sugar Diet Intake Programming Inflammatory and Oxidative Parameters of Reproductive Health in Male Offspring.

Parental nutrition can impact the health of future generations, programming the offspring for the development of diseases. The developing germ cells of the offspring could be damaged by the maternal or the paternal environment. The germ cells in development and their function could be affected by nutritional adversity and therefore, harm the health of subsequent generations. The paternal or maternal intake of high-fat diets has been shown to affect the reproductive health of male offspring, leading to imbalance in hypothalamic-pituitary-gonadal axis, testicular oxidative stress, low testosterone production, and changes in sperm count, viability, motility, and morphology. There is a need for studies that address the combined effects of diets with a high-fat and high-sugar (H) content by both progenitors on male reproduction. In this context, our study evaluated epigenetic parameters and the inflammatory response that could be associated to oxidative stress in testis and epididymis of adult offspring. 90 days-old male rats were divided according to the combination of the parental diet: CD (control paternal and maternal diet), HP (H paternal diet and control maternal diet), HM (H maternal diet and control paternal diet) and HPM (H paternal and maternal diet).We evaluated serum levels of testosterone and FSH; testicular gene expression of steroidogenic enzymes Star and Hsd17b3 and epigenetic markers Dnmt1, Dnmt3a, Dnmt3b, and Mecp2; testicular and epididymal levels of TNF-α, IL-6, IL-10, and IL-1ß; testicular and epididymal activity of SOD, CAT, and GST; the oxidative markers MDA and CP; the daily sperm production, sperm transit time, and sperm morphology. Testicular epigenetic parameter, inflammatory response, oxidative balance, and daily sperm production of the offspring were affected by the maternal diet; paternal diet influenced serum testosterone levels, and lower daily sperm production was exacerbated by the interaction effect of both parental intake of high-fat high-sugar diet in the testis. There was isolated maternal and paternal effect in the antioxidant enzyme activity in the cauda epididymis, and an interaction effect of both parents in protein oxidative marker. Maternal effect could also be observed in cytokine production of cauda epididymis, and no morphological effects were observed in the sperm. The potential programming effects of isolated or combined intake of a high-fat high-sugar diet by the progenitors could be observed at a molecular level in the reproductive health of male offspring in early adulthood.

Resveratrol effects in oral cancer cells: a comprehensive review.

Oral cancer is a very common tumor worldwide with high incidence and mortality. The treatment of oral cancer involves surgery, radio- and chemotherapy; however, high failure rates and toxicity are noticed. Thus, the search of new drugs aiming a more effective treatment is welcomed. Natural products present chemopreventive and anti-cancer effects. Resveratrol is a naturally occurring antioxidant that contains several health benefits, including anti-inflammatory and antiproliferative activities. This review discusses the different action mechanisms of resveratrol related in the in vitro and in vivo studies using models of oral cancer.

Morphological damage in Sertoli, myoid and interstitial cells in a mouse model of mucopolysaccharidosis type I (MPS I).

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease caused by a mutation in the IDUA gene, which codes α-L-iduronidase (IDUA), a lysosomal hydrolase that degrades two glycosaminoglycans (GAGs): heparan sulfate (HS) and dermatan sulfate (DS). GAGs are macromolecules found mainly in the extracellular matrix and have important signaling and structural roles which are essential to the maintenance of cell and tissue physiology. Nondegraded GAGs accumulate in various cell types, which characterizes MPS I as a multisystemic progressive disease. Many tissues and vital organs have been described in MPS I models, but there is a lack of studies focused on their effects on the reproductive tract. Our previous studies indicated lower sperm production and morphological damage in the epididymis and accessory glands in male MPS I mice, despite their ability to copulate and to impregnate females. Our aim was to improve the testicular characterization of the MPS I model, with a specific focus on ultrastructural observation of the different cell types that compose the seminiferous tubules and interstitium. We investigated the testicular morphology of 6-month-old male C57BL/6 wild-type (Idua+/+) and MPS I (Idua-/-) mice. We found vacuolated cells widely present in the interstitium and important signs of damage in myoid, Sertoli and Leydig cells. In the cytoplasmic region of Sertoli cells, we found an increased number of vesicles with substrates under digestion and a decreased number of electron-dense vesicles similar to lysosomes, suggesting an impaired flux of substrate degradation. Conclusions: Idua exerts an important role in the morphological maintenance of the seminiferous tubules and the testicular interstitium, which may influence the quality of spermatogenesis, having a greater effect with the progression of the disease.

Evidence that glycosaminoglycan storage and collagen deposition in the cauda epididymidis does not impair sperm viability in the Mucopolysaccharidosis type I mouse model.

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease caused by a deficiency of the lysosomal hydrolase, α-L-iduronidase (IDUA). IDUA degrades heparan and dermatan sulfates, two types of glycosaminoglycan (GAG), important signalling and structural molecules of the extracellular matrix. Because many cell types store GAGs, MPS I has been investigated in human and animal models. Enzyme replacement therapy is available for MPS I patients and has improved their life expectancy, allowing them to achieve reproductive age. The aim of this study was to evaluate epididymal and sperm morphology and function in a murine model of MPS I. We used C57BL Idua+/+ and Idua-/- adult male mice (6 months old) to investigate epididymal morphology, sperm ultrastructure, GAG characterisation and mating competence. Epithelial GAG storage, especially in the cauda epididymidis, was seen in Idua-/- mice. Regardless of the morphologic change and GAG storage found in the cauda epididymis, sperm morphology and motility were normal, similar to wild types. In the interstitium, vacuolated cells were found in addition to deposits of GAGs. Mating was not impaired in Idua-/- males and litter sizes were similar between groups. At the time point of the disease evaluated, the deficiency in IDUA affected the morphology of the epididymis in male Idua-/- mice, whereas sperm appearance and motility and the male's capacity to mate and impregnate females were preserved.

Role of polyphenols and nonpolyphenols against toxicity induced by fluoride: a comprehensive review.

Since its discovery as an antimicrobial agent, fluoride has been used in the control of dental caries. Many studies have shown that the chronic exposure of fluoride in high concentrations causes adverse effects in multiple organs; the use of bioactive compounds present in foods as a tool to mitigate the effects of fluoride could potentially be useful for populations in different parts of the world are exposed to fluoride in a chronic and systemic way. Thus, the aim of this comprehensive review is to present and discuss the published papers that focused on the use of polyphenols and nonpolyphenols that can mitigate the harmful activities promoted by fluoride exposure. Certainly, these data will contribute toward a better understanding of the role of food compounds in the pathological outcomes induced by fluoride. The new information will be added to that already available for regulatory purposes as a safe way to promote oral healthcare and prevent oral carcinogenesis.

Grape skin extract mitigates tissue degeneration, genotoxicity, and oxidative status in multiple organs of rats exposed to cadmium.

The aim of this study was to investigate whether grape skin extract can mitigate the noxious activities induced by cadmium exposure in multiple organs of rats. For this purpose, histopathological analysis for the liver, genotoxicity, and oxidative status in the blood and liver were investigated in this setting. A total of 20 Wistar rats weighing 250 g, on average, and 8 weeks of age were distributed into four groups (n=5) as follows: control group (nontreated group); cadmium group (Cd); and grape skin extract groups (Cd+GS) at 175 or 350 mg/l. Histopathological analysis in liver showed that animals treated with grape skin extract showed improved tissue degeneration induced by cadmium intoxication. Genetic damage was reduced in blood and hepatocytes as indicated by comet and micronucleus assays in animals treated with grape skin extract. Copper-zinc superoxide dismutase and cytochrome c gene expression increased in groups treated with grape skin extract in liver cells. Grape skin extract also reduced the 8-hydroxy-2'-deoxyguanosine levels in liver cells compared with the cadmium group. Taken together, our results indicate that grape skin extract can mitigate tissue degeneration, genotoxicity, and oxidative stress induced by cadmium exposure in multiple organs of Wistar rats.

Fluoride Induces Apoptosis in Mammalian Cells: In Vitro and In Vivo Studies.

Apoptosis is genetically programmed cell death, an irreversible process of cell senescence with characteristic features different from other cellular mechanisms of death such as necrosis. In the last years, apoptosis has been extensively studied in the scientific literature, because it has been established that apoptosis plays a crucial role following the time course of chronic degenerative diseases, such as cancer. Thus, several researchers have strugged to detect what chemical agents are able to inter fere with the apoptotic process. Thus, the purpose of this literature review is to assess if fluoride induces apoptosis in mammalian cells using in vivo and in vitro test systems. Certain mammalian cell types such as oral cells, blood and brain were exetensively investigated; the results showed that fluoride is able to induce apoptosis in both intrinsinc and extrinsic pathways. Moreover, other cells types have been poorly investigated such as bone, kidney and reproductive cells with conflicting results so far. Therefore, this area needs further investigation for the safety of human populations exposed to fluoride in a chronic way, as for example in developing countries.

Genotoxicity Induced by Dental Materials: A Comprehensive Review.

Genotoxicity is the capacity of an agent to produce damage in the DNA molecule. Considering the strong evidence for a relationship between genetic damage and carcinogenesis, evaluation of genotoxicity induced by dental materials is necessary for elucidating the true health risks to patients and professionals. The purpose of this article was to provide a comprehensive review of genotoxicity induced by dental materials. All published data showed some evidence of genotoxicity, especially related to dental bleaching, restorative materials and endodontic compounds. Certainly, such information will be added to that already established for regulatory purposes as a safe way to promote oral healthcare and prevent oral carcinogenesis.

Antimutagenic and antigenotoxic potential of grape juice concentrate in blood and liver of rats exposed to cadmium.

The aim of this study was to evaluate the antimutagenic and antigenotoxic potential of grape juice concentrate in rodent organs exposed to cadmium chloride intoxication. A total of 15 Wistar rats were distributed into three groups (n = 5), as follows: control group (CTRL; nontreated group), cadmium group (Cd), and cadmium-grape juice group (Cd + GJ). Exposed animals received intraperitoneal injection of cadmium chloride (1.2 mg/kg body weight) diluted in water and, after 15 days, Cd + GJ group received grape juice concentrate for 15 days, by gavage (0.8 mL, 1.18 mg of polyphenols kg(-1) day(-1)). Grape juice concentrate was able to decrease genotoxic effects induced by cadmium in peripheral blood and liver cells as depicted by single cell gel (comet) and micronucleus assays. A decrease for anti-8-hydroxy-20-deoxyguanosine (8OHdG) expression in hepatocytes of animals exposed to cadmium and treated with grape juice concentrate was also detected. Higher CuZn-SOD activity was observed in liver cells of the Cd + GJ group. No remarkable differences were seen regarding Mn-SOD activity among groups. Taken together, our results demonstrate that grape juice concentrate was able to exert antimutagenic and antigenotoxic activities in blood and liver cells of rats exposed to cadmium.

Chemopreventive activity of apple extract following medium-term oral carcinogenesis assay induced by 4-nitroquinoline-1-oxide.

OBJECTIVE: The aim of this study was to evaluate the chemopreventive activity of an apple extract following medium-term oral carcinogenesis assay induced by 4-nitroquinoline-1-oxide (4NQO). METHODS: A total of 30 male Wistar rats were distributed into five groups as follows (n=6 per group): Group 1, negative control group (non-treated group); Group 2, received 4NQO during 8 weeks in drinking water and treated with apple extract at 1% by gavage between the first and fourth weeks daily (initiation phase); Group 3, received 4NQO for 8 weeks in drinking water and treated with apple extract by gavage at 1% between the fifth and eighth weeks daily (promotion phase); Group 4, received apple extract at 1% by gavage for 8 consecutive weeks only; and Group 5, received 4NQO for 8 weeks in drinking water daily. RESULTS: Histopathological analysis revealed decreased hyperplasic lesions in Group 2 when compared with Group 5. Likewise, decreased dysplastic lesions in Group 3 were observed when compared with Group 5. In Groups 2 and 3, decreased COX-2 and TNF-alpha gene expressions were observed when compared with Group 5. Cytochrome c and caspase 3 levels increased in Groups 2 and 3 when compared with Group 5. CONCLUSION: In conclusion, our results demonstrate that apple extract suppresses rat tongue carcinogenesis as a result of anti-inflammatory activity and apoptosis through the intrinsic mitochondrial pathway.

The chemopreventive activity of apple against carcinogenesis: antioxidant activity and cell cycle control.

Apples and their derivatives are rich in phytochemicals, including flavonoids (catechins, flavonols, quercetin) and phenolic acids (quercetin glycosides, catechin, epicatechin, procyanidins), vitamins, and fibers, that confer an important antioxidant property. Chemoprevention is defined by the use of natural or synthetic agents to interfere with the progression, reverse, or inhibit carcinogenesis, thereby reducing the risk of developing clinically invasive disease. The aim of this article is to present data generated from the use of apples as a chemopreventive agent in carcinogenesis using in-vivo and in-vitro test systems. Apple and its bioactive compounds can exert chemopreventive properties as a result of antioxidant activity and cell cycle control. However, future focus of research on apple such as identifying the specific phytochemical responsible for the anticarcinogenic effect, timing of consumption, and adequate amount of apples to achieve the best preventive effect using human large randomized-controlled trials is needed. Furthermore, animal studies are also relevant for better understanding the role of this fruit in human health as well as modulation of degenerative diseases such as cancer. Therefore, this area warrants further investigation as a new way of thinking, which would apply not only to apples but also to other fruit used as promising therapeutic agents against human diseases.

Grape juice concentrate protects reproductive parameters of male rats against cadmium-induced damage: a chronic assay.

The aim of the present study was to investigate the effects of long-term grape juice concentrate (GJC) consumption, in two dosages, on the reproductive parameters of cadmium-exposed male rats. The effects of the concentrate on body mass gain, plasma testosterone levels, reproductive organ weights, daily sperm production, sperm morphology, testis histopathological and histomorphometrical parameters, and testicular antioxidant markers were investigated. Wistar rats (n 54) were distributed into six groups: CdCl2; cadmium and grape juice I (1·18 g/kg per d); cadmium and grape juice II (2·36 g/kg per d); grape juice I (1·18 g/kg per d); grape juice II (2·36 g/kg per d); control. A single dose of CdCl2 (1·2 mg/kg body weight (BW)) was injected intraperitoneally and the grape juice was administered orally for 56 d. The results indicated that cadmium changed all reproductive and antioxidant parameters. At dosage I (1·18 g/kg BW), GJC consumption did not show the effects against cadmium-induced damages. In contrast, at dosage II (2·36 g/kg BW), the GJC improved the gonadosomatic index (P= 0·003), serum testosterone levels (P= 0·001), the relative weight of epididymis (P= 0·013) and ventral prostate (P= 0·052), the percentage of normal sperm (P= 0·001), and histopathological and histomorphometrical parameters. In addition, at this dosage, normalisation of the enzymatic activity of superoxide dismutase (P= 0·001) and of testicular levels of glutathione (P= 0·03) were observed. The parameters of the non-exposed rats did not depict significant alterations. In conclusion, the product was able to act as a protector of reproductive function against cadmium-induced damage. Such a property was expressed in a dose-dependent manner as the more effective dose was dosage II. The GJC acted possibly by antioxidant mechanisms.

Use of grape polyphenols against carcinogenesis: putative molecular mechanisms of action using in vitro and in vivo test systems.

Polyphenols are present in foods and beverages and are related to sensorial qualities such as color, bitterness, and astringency, which are relevant in wine, tea, grape juice, and other products. These compounds occur naturally in forms varying from simple phenolic acids to complex polymerized tannins. Thus, it is reasonable to expect that grape-derived products elaborated in the presence of skins and seeds, such as wine and grape juice, are natural sources of flavonoids in the diet. Carcinogenesis is a multistep process that is characterized by genetic, epigenetic, and phenotypic changes. With increasing knowledge of these mechanisms, and the conclusion that most cases of cancer are preventable, efforts have focused on identifying the agents with potential anticancer properties. The use of grape polyphenols against the carcinogenesis process seems to be a suitable alternative for either prevention and/or therapeutic purposes. The aim of this article is to show the molecular data generated from the use of grape polyphenols against carcinogenesis using in vivo and in vitro test systems.

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.

Low-level laser therapy improves repair following complete resection of the sciatic nerve in rats.

The aim of this study is to analyze the effects of low-level laser therapy (LLLT) on the regeneration of the sciatic nerve in rats following a complete nerve resection. Male Wistar rats were divided into a control injury group, injury groups irradiated with a 660-nm laser at 10 or 50 J/cm(2), and injury groups irradiated with an 808-nm laser at 10 or 50 J/cm(2). Treatment began 24 h following nerve resection and continued for 15 days. Using the sciatic functional index (SFI), we show that the injured animals treated with 660 nm at 10 and 50 J/cm(2) had better SFI values compared with the control injury and the 808-nm groups. Animals irradiated with the 808-nm laser at 50 J/cm(2) show higher values for fiber density than do control animals. In addition, axon and fiber diameters were larger in animals irradiated with 660 nm at 50 J/cm(2) compared to the control group. These findings indicate that 660-nm LLLT is able to provide functional gait recovery and leads to increases in fiber diameter following sciatic nerve resection.

Chromosome analysis of five Brazilian species of poison frogs (Anura: Dendrobatidae).

Dendrobatid frogs have undergone an extensive systematic reorganization based on recent molecular findings. The present work describes karyotypes of the Brazilian species Adelphobates castaneoticus, A. quinquevittatus, Ameerega picta, A. galactonotus and Dendrobates tinctorius which were compared to each other and with previously described related species. All karyotypes consisted of 2n = 18 chromosomes, except for A. picta which had 2n = 24. The karyotypes of the Adelphobates and D. tinctorius species were highly similar to each other and to the other 2n = 18 previously studied species, revealing conserved karyotypic characteristics in both genera. In recent phylogenetic studies, all Adelphobates species were grouped in a clade separated from the Dendrobates species. Thus, we hypothesized that their common karyotypic traits may have a distinct origin by chromosome rearrangements and mutations. In A. picta, with 2n = 24, chromosome features of pairs from 1 to 8 are shared with other previously karyotyped species within this genus. Hence, the A. picta data reinforced that the C-banding pattern and the NOR location are species-specific traits in the genus Ameerega. Moreover, the Ameerega monophyletism proposed by previous phylogenetic studies indicates that the karyotypic differences among species in this genus result from a long divergence time.

Protective effects of green tea against hepatic injury induced by high-cholesterol diet in rats: histopathological analysis, oxidative DNA damage and COX-2 expression.

PURPOSE: The goal of this study was to investigate whether daily administration of green tea is able to protect the liver injury induced by cholesterol. METHODS: Male Wistar rats (n = 24) were distributed into four groups: group 1, negative control; group 2, cholesterol at 1% (w/w) in the diet treated for 5 weeks; group 3, cholesterol at 1% treated for 5 weeks and green tea at 1% (w/v) in drinking water in the last week only and group 4, cholesterol and green tea at 1% in drinking water for 5 weeks. RESULTS: The results pointed out that treatment with green tea in the last week (group 3) showed mild degenerative changes of liver tissue in cholesterol exposed group when compared to group 2. Green tea aqueous extract was not able to reduce cholesterol levels, that is, no significant statistical differences (p > 0.05) were noticed when compared to positive control group. Nevertheless, green tea was able to decrease oxidative deoxyribonucleic acid (DNA) damage either to peripheral blood or to liver cells as depicted by significant statistical differences (p < 0.05) in the mean tail moment between groups treated with green tea and cholesterol and cholesterol only. Furthermore, histomorphometric analysis of COX-2 expression revealed that in groups exposed to green tea they were significantly decreased (p < 0.05), regardless of time exposure adopted. CONCLUSION: Taken together, our results suggest that daily administration of green tea for at least 7 days displays some preventive properties as indicated by COX-2 downregulation and decreased oxidative DNA damage.

Differential response related to genotoxicity in multiple organs of cirrhotic rats.

PURPOSE: The aim of this study was to use the single cell gel (comet) assay to investigate whether blood, liver, heart, kidney, and brain are particularly sensitive organs for DNA damage in cirrhotic rats to predict genetic instability induced by cirrhosis. METHODS: A total of 16 male Wistar rats (negative control, n = 8; experimental, n = 8) were submitted to bile duct ligation during 28 days. RESULTS: Cirrhosis was able to induce genetic damage in liver and brain cells, as depicted by the mean tail moment. No genetic damage was induced in blood, heart, or kidney cells (i.e., no significant statistically differences were noticed when compared with negative control). CONCLUSIONS: In conclusion, our results suggest that cirrhosis could contribute to DNA damage in liver and brain cells.

Grape juice concentrate prevents oxidative DNA damage in peripheral blood cells of rats subjected to a high-cholesterol diet.

The goal of the present study was to investigate whether subchronic treatment with grape juice concentrate is able to protect liver and peripheral blood cells against cholesterol-induced injury in rats. The effects of the grape juice concentrate treatment on histopathological changes, immunohistochemistry for cyclo-oxygenase-2 (COX-2), and basal and oxidative DNA damage induced by H2O2 using a single-cell gel (comet) assay were evaluated. Male Wistar rats (n 18) were divided into three groups: group 1--negative control; group 2--cholesterol at 1 % (w/w) in their diet, treated for 5 weeks; group 3--cholesterol at 1 % in their chow, treated for 5 weeks, and grape juice concentrate at 222 mg/d in their drinking-water in the final week only. The results indicated that the treatment with grape juice concentrate did not show remarkable differences regarding liver tissue in group 3 compared with group 2. However, grape juice concentrate was able to decrease oxidative DNA damage induced by H2O2 in peripheral blood cells, as depicted by the tail moment results. COX-2 expression in the liver did not show statistically significant differences (P>0·05) between groups. Taken together, the present results suggest that the administration of subchronic grape juice concentrate prevents oxidative DNA damage in peripheral blood cells.