Cytotoxicity, Inflammatory Activity, and Angiogenesis Are Induced by Different Silicone Implants.

BACKGROUND/AIM: The aim of this study was to investigate cytotoxicity, inflammatory response, and angiogenesis induced by silicone gel breast implants with different textured surfaces in vitro and in vivo. MATERIALS AND METHODS: In the in vitro study, murine fibroblast cells (L929) were cultured for 1, 3, and 5 days with silicone membranes of three different textures: nanotextured, microtextured, and silicone foam. In the in vivo study, a total of 30 male rats (Rattus, norvegicus, albinos, Wistar) were distributed into three groups (10 animals per group), with 2 implants in each rat: nanotextured silicone gel breast implants group, microtextured silicone gel breast implants group, and silicone gel breast foam implants group. RESULTS: The Alamar Blue assay detected higher viability of cells cultured in the presence of nanotextured silicone surface for 1 and 3 days. The MTT assay showed higher cytotoxicity of silicone foam after 1 and 3 days of exposure. Nanotextured silicone breast implants induced a more prolonged inflammatory response, denoting a delay in the healing process and subsequent organization of the fibrous capsule as depicted by the collagen fiber types found. VEGF expression did not differ between experimental groups. CONCLUSION: Gel foam breast implants are more biocompatible when compared to micro- or nano-textured silicone breast implants.

Protective Effect of Grape and Apple Juices against Cadmium Intoxication in the Kidney of Rats.

BACKGROUND: The objective of this study was to evaluate protective effect of grape and apple juices against toxicity induced by cadmium in the kidney of rats. METHODS: A total of 20 male-Wistar rats were distributed into four groups (n=5): Control group: animals received an intraperitoneal (i.p.) injection of 0.9% saline solution and after 15 days, 1 mL of water was administered for 15 days, via gavage; Cadmium group: animals received an intraperitoneal injection of cadmium chloride (1.2 mg/kg) and after 15 days, 1 mL of water was administered for 15 days via gavage; Cadmium+Grape Juice: animals received an i.p. injection of cadmium chloride (1.2 mg/kg), and after 15 days, 0.8 mL of grape juice was administered for 15 days, via gavage; Cadmium+Apple Juice: animals received i.p. injection of cadmium chloride (1.2 mg/kg) and after 15 days, 1.0 mL of apple juice was administered for 15 days, via gavage. RESULTS: Histopathological analysis revealed severe tubular lesion and necrosis in the group exposed to cadmium, while animals exposed to grape or apple juices showed a significant reduction of tissue injury. 8-OHdG immunoexpression, DNA damage, cytochrome C and catalase gene expressions and Toll like signaling pathway (TLR2, and pIKKα/ß) decreased in animals treated with grape juice when compared to cadmium group. CONCLUSION: Taken together, we conclude that grape and apple juices had a protective effect by means of antioxidant, antigenotoxic actions and for promoting tissue regeneration in the kidney of rats following cadmium intoxication.

Therapeutical properties of Mimosa caesalpiniifolia in rat liver intoxicated with cadmium.

The aim of this study was to evaluate the therapeutic properties of Mimosa caesalpiniifolia in liver of rats exposed to cadmium under morphological, oxidative, inflammatory, and mutagenic parameters. A total of 40 Wistar rats (90 days, ~ 250 g) were distributed into eight groups (n = 5) as follows: (i) control; (ii) cadmium: cadmium chloride injection at 1.2 mg/kg; (iii) Mimosa extract: treatment with Mimosa extract at 250 mg/kg; (iv) Mimosa fraction: treatment with Mimosa acetate fraction at 62.5 mg/kg; (v) cadmium and Mimosa extract 62.5: submitted to cadmium chloride at 1.2 mg/kg injection and treatment with Mimosa extract at 62.5 mg/kg; (vi) cadmium and Mimosa extract 125: subjected to cadmium chloride at 1.2 mg/kg injection and treatment with Mimosa extract at 125 mg/kg; (vii) cadmium and Mimosa 250 extract: submitted to cadmium chloride 1.2 mg/kg injection and treatment with Mimosa extract at 250 mg/kg; (viii) cadmium treated with fraction of Mimosa acetate: submitted to cadmium chloride 1.2 mg/kg injection and treatment with acetate fraction of Mimosa extract at 62.5 mg/kg. In the animals intoxicated with cadmium and treated with fraction [62.5], increased expression of SOD-Mn reduced frequency of binucleated hepatocytes, karyolysis, and karyorrhexis, besides the antimutagenic and antioxidant action. The extract [62.5] was cytoprotective, antimutagenic, and reduced karyolysis. The extract [125] was cytoprotective, antioxidant, antifibrotic, anti-inflammatory, and reduced frequency of binucleated hepatocytes, while extract [250] was cytotoxic and mutagenic. In summary, the extract of Mimosa exerts some therapeutic properties in hepatic tissue after Cd intoxication, but only when it is administrated at intermediate doses. Probably, a high content of polyphenols in the EHM [250] and Fr-EtOAc groups exert pro-oxidant activities in the liver particularly when associated with Cd.

Evaluation of the Chemopreventive Activity of Grape Skin Extract Using Medium-term Oral Carcinogenesis Assay Induced by 4-Nitroquinoline 1-Oxide.

BACKGROUND/AIM: The aim of this study was to evaluate the chemoprotective potential of grape skin extract following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO). MATERIALS AND METHODS: Male Wistar rats were distributed into four groups (n=5, per group): Control Group: free access to commercial diet and drinking water for 12 weeks; 4NQO Group: received 4NQO diluted in drinking water daily, for 12 weeks; Grape Skin Extract Group: free access to water and received grape skin extract incorporated with diet for 12 weeks; 4NQO + Grape Skin Extract Group: received 4NQO in drinking water daily and grape extract incorporated with diet for 12 weeks. RESULTS: Animals treated with grape skin extract revealed a significant reduction in epithelial dysplasia. Also, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and ki-67 immunoexpression was reduced in animals treated with grape skin extract. Western blot analysis showed a significant decrease of p-NFκB p50 and MyD88 protein expression in the groups treated with grape skin extract. Copper-zinc superoxide dismutase, manganese superoxide dismutase, and catalase gene expression did not present any statistically significant differences (p>0.05). CONCLUSION: Grape skin extract displayed chemopreventive activity in oral carcinogenesis assays as depicted by its antioxidant, anti-proliferative and anti-inflammatory properties.

Protective effects of purple carrot extract (Daucus carota) against rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.

The aim of this study was to evaluate the chemopreventive potential of purple carrot extract following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO). For this purpose, histopathological analysis, proliferative status, antioxidant activity and inflammatory status were investigated in this setting. A total of 20 male rats were distributed into four groups as follows (n = 5 per group): Group 1-free access to water and commercial diet for 12 weeks; Group 2-received 4NQO at 50 ppm dose in drinking water daily and commercial diet for 12 weeks; Group 3-free access to water and received diet supplemented with purple carrot extract (0.1 g/kg) for 12 weeks; and Group 4-received 4NQO at 50 ppm dose in drinking water daily and diet supplemented with purple carrot extract (0.1 g/kg) for 12 weeks. Histopathological analysis revealed that animals treated with purple carrot extract reduced the oral lesions such as dysplasia and squamous cell carcinoma. Animals with oral pre-neoplastic lesions and treated with purple carrot extract decreased ki-67 and 8-OHdG immunoexpression. Moreover, pNFκBp50 and MyD88 protein expressions were decreased after purple carrot treatment associated or not with 4NQO exposure. SOD-Mn mRNA levels increased with treatment with purple carrot extract as well. In conclusion, our results demonstrated that purple carrot extract was able to protect oral lesions induced by 4NQO in Wistar rats as a result of antioxidant activity, anti-inflammatory potential and antiproliferative and antimutagenic actions.

Protective effect of grape or apple juices in bone tissue of rats exposed to cadmium: role of RUNX-2 and RANK/L expression.

The aim of this study was to investigate if grape or apple juices are able to protect bone tissue of rats exposed to cadmium. For this purpose, histopathological analysis and immunohistochemistry for RUNX-2 and RANK-L were investigated in this setting. A total of 20 adult Wistar rats were distributed into four groups (n = 5), as follows: control group, cadmium group, cadmium and grape juice group, and Cadmium and apple juice group. Control group received a single intraperitoneal (i.p.) water injection. Cadmium group received a single i.p. injection of cadmium chloride (1.2 mg/kg body weight) diluted in water. Cadmium and grape juice and cadmium and apple juice groups received a single i.p. injection of cadmium chloride (1.2 mg/kg body), and after 15 days, the rats were treated with grape or apple juices for 15 days, by gavage. All animals were euthanized 30 days after the beginning of experiment. Histopathological analysis in rat femur revealed extensive bone loss in rats intoxicated with cadmium. Grape or apple juices were able to increase bone formation. Cadmium inhibited RUNX-2 immunoexpression whereas cadmium increased RANK-L immunoexpression in rat bone cells. Grape or apple juices increased RUNX-2 and decreased RANK-L immunoexpression after cadmium intoxication. Taken together, our results demonstrate that grape or apple juices are able to exert therapeutic activity following cadmium intoxication in rat bone tissue as result of stimulatory effect of bone formation by RUNX-2 upregulation and RANK-L downregulation.

The Anti-Inflammatory Potential of Mimosa caesalpiniifolia Following Experimental Colitis: Role of COX-2 and TNF-Alpha Expression.

The aim of this study was to evaluate the preventive and/or protective action of Mimosa caesalpiniifolia (M. caesalpiniifolia) following experimental colitis in rats. The rats were randomized into ten groups (n=10 per group), as follows: G1 - Sham group:; G2 - TNBS group; G3, G4 -colitis and treated with hydroalcoholic extract of M. caesalpiniifolia 250 mg/kg/day after and before/after inducing colitis, respectively; G5, G6 - colitis and treated with hydroalcoholic extract of M. caesalpiniifolia at 125 mg/kg/day after and before/after inducing colitis respectively; G7,G8 - colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively; G9,G10 - colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively. Rats treated with hydroalcoholic extract of M. caesalpiniifolia for both doses showed lower tissue damage in the distal colon. Ethylacetate fraction was effective at the highest dose only when administrated after inducing colitis. A downregulation of COX-2 was detected to rats suffering colitis and treated with M. caesalpiniifolia at high dose. On the other hand, TNF-alpha immunoexpression decreased in groups treated with M. caesalpiniifolia at low dose after inducing colitis. In summary, our results suggest that M. caesalpiniifolia attenuated the lesions of the colon, reduced inflammation, and modulates the expression of COX-2 and TNF-α during chronic colitis induced by TNBS when using for therapeutic purposes on a dose-dependent manner.

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.

Genotoxicity, mutagenicity and cytotoxicity of carotenoids extracted from ionic liquid in multiples organs of Wistar rats.

The ionic liquid or melted salt 1-Butyl-3-methylimidazolium is an alternative process to extract natural pigments, such as carotenoids. Lycopene represents 80-90% of total of carotenoids presents in tomatoes and it has been widely studied due its potent antioxidant action. The aim of this study was to evaluate genotoxicity, mutagenicity and cytotoxicity of carotenoids extracted from ionic liquid using experimental model in vivo. For this purpose, a total of 20 male Wistar rats were distributed into four groups (n=5), as follows: control group; received a corresponding amount of corn oil for 7days by intragastric gavage (i.g.), ionic liquid group, received 10mgkg-1 body weight for 7days by gavage; 10mg carotenoids group, received 10mgkg-1 bw dissolved in corn oil for 7days by gavage and 500mg carotenoids group, received 500mgkg-1 bw dissolved in corn oil for 7days by gavage. Rat liver treated with ionic liquid exhibited moderate histopathological changes randomly distributed in the parenchyma, such as cytoplasmic eosinophilia, apoptotic bodies, inflammatory infiltrate and focal necrosis. DNA damage was found in peripheral blood and liver cells of rats treated with ionic liquid or carotenoids at 500mg. An increase of micronucleated cells and 8-OhDG immunopositive cells were also detected in rats treated with carotenoids at 500mg. In summary, our results demonstrate that recommended dose for human daily intake of carotenoids extracted by ionic liquid did not induce genotoxicity, mutagenicity and cytotoxicity in multiple organs of rats.

Mimosa (Mimosa caesalpiniifolia) prevents oxidative DNA damage induced by cadmium exposure in Wistar rats.

The Mimosa (Mimosa caesalpiniifolia) is a plant native from South America; it is used in the traditional medicine systems for treating bacterial, fungal, parasitic and inflammatory conditions. The aim of this study was to evaluate the antigenotoxic and antioxidant activities induced by mimosa (M. caesalpiniifolia) in multiple rodent organs subjected to intoxication with cadmium chloride. A total of 40 Wistar rats (8 weeks old, 250 g) were distributed into eight groups (n = 5), as follows: Control group (non-treated group, CTRL); Cadmium exposed group (Cd); cadmium exposure and treated with extract at 62.5 mg/kg/day; cadmium exposure and treated with extract at 125 mg/kg/day; cadmium exposure and treated with extract at 250 mg/kg/day; cadmium exposure and treated with ethyl acetate fraction at 62.5 mg/kg/day. For evaluating the toxicogenetic potential of mimosa, two groups were included in the study being treated with extract at 250 mg/kg/day and acetate fraction of mimosa at 62 mg/kg/day, only. Extract of mimosa at concentrations of 62.5 and 125 mg decreased DNA damage in animals intoxicated with cadmium when compared to cadmium group. In a similar manner, treatment with ethyl acetate fraction of mimosa at 62.5 mg concentration in animals previously exposed to cadmium reduced genetic damage in peripheral blood cells. In a similar manner, the treatment with ethyl acetate fraction reduced DNA damage in liver cells. Oxidative DNA damage was reduced to animals exposed to cadmium and treated with 125 mg of extract as well as those intoxicated to cadmium and treated with 62.5 of acetate fraction of mimosa. Taken together, our results indicate that mimosa prevents genotoxicity induced by cadmium exposure in liver and peripheral blood cells of rats as a result of antioxidant activity.

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.

Genotoxicity and cytotoxicity induced by municipal effluent in multiple organs of Wistar rats.

The aim of this study was to evaluate cytotoxicity and genotoxicity in multiple organs of rats induced by municipal effluent released by submarine outfall in city of Santos. A total of 20 male Wistar rats were exposed to effluents by drinking water ad libitum at concentrations of 0, 10, 50, and 100 % for 30 days. Microscopic analysis revealed severe lesions such as necrosis and hemorrhagic areas in liver and kidney from animals exposed to effluent at 50 and 100 % concentration. DNA damage in peripheral blood, liver, and kidney cells were detected by comet assay at higher concentrations of effluent. Moreover, a decrease DNA repair capacity was detected in liver cells. Significant statistical differences (p<0.05) for micronucleated cells from liver were noticed at 50 % concentration of effluent. Taken together, our results demonstrate that municipal effluent is able to induce cytotoxicity and genotoxicity in multiple organs of Wistar rats.

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.

Anti-tumor activity of grape juice concentrate in the rat tongue two-stage initiation-promotion protocol induced by 4-nitroquinoline 1-oxide.

The aim of this study was to evaluate the anti-tumor activity of grape juice concentrate following medium-term oral carcinogenesis assay induced by 4-nitroquinoline 1-oxide (4NQO). 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 grape juice concentrate at 1% dose by gavage for eight consecutive weeks; Group 3 - received 4NQO for 8 weeks at 20 ppm dose in drinking water daily; Group 4 - received 4NQO at 20 ppm dose during 8 weeks in drinking water and treated with grape juice concentrate at 1% dose orally by gavage for first 4 weeks after 4-NQO administration; Group 5 - received 4NQO at 20 ppm dose for 8 weeks in drinking water and treated with grape juice concentrate at 1% dose orally by gavage between the 5th and 8th weeks daily. Histopathological analysis revealed a decrease in hyperplasic and dysplastic lesions in Group 4. Groups 4 and 5 showed decreased COX-2 and TNF-alpha and eNOS gene expression. Grape juice concentrate also increased SOD Cu/Zn and catalase expression. However, Ki-67 immunoexpression was reduced at the promotion step of oral carcinogenesis (G5). Taken together, our results demonstrate that grape juice concentrate modulates rat tongue carcinogenesis as a result of anti-inflammatory activity, antioxidant activity and down-regulation of oral cells proliferation.

Nandrolone decanoate induces genetic damage in multiple organs of rats.

To evaluate the impact potential of nandrolone decanoate on DNA damage in multiple organs of Wistar rats by means of single-cell gel (comet) assay and micronucleus test. A total of 15 animals were distributed into three groups of five animals each as follows: control group = animal not exposed to nandrolone decanoate; experimental group = animals exposed to nandrolone decanoate for 24 h at 5 mg/kg subcutaneously; and experimental group = animals exposed to nandrolone decanoate for 24 h at 15 mg/kg subcutaneously. Significant statistical differences (p < 0.05) were noted in peripheral blood, liver, and heart cells exposed to nandrolone decanoate at the two doses evaluated. A clear dose-response relationship was observed between groups. Kidney cells showed genetic damage at only the highest dose (15 mg/kg) used. However, micronucleus data did not show remarkable differences among groups. In conclusion, the present study indicates that nandrolone decanoate induces genetic damage in rat blood, liver, heart, and kidney cells as shown by single-cell gel (comet) assay results.

Metastasis from oral cancer: an overview.

Oral cancer is a common neoplasm worldwide. Its incidence and mortality have also increased over the past decades. It is characterized by poor prognosis and a low survival rate despite sophisticated surgical and radiotherapeutic modalities. Metastasis of oral cancer is a complex process involving detachment of cells from tumor tissue, regulation of cell motility and invasion, proliferation and evasion through the lymphatic system or blood vessels. In this review, we will focus on the current knowledge in metastasis from oral cancer regarding facts, such as incidence; stage, histopathology and grade of primary tumor; clinical manifestations; diagnosis; and treatment. Certainly, such information will contribute to the understanding of oral cancer pathogenesis.

The role of canonical WNT signaling pathway in oral carcinogenesis: a comprehensive review.

Oral cancer is a common neoplasm worldwide. The incidence and mortality have also increased in recent decades. It is characterized by poor prognosis and a low survival rate despite sophisticated surgical and radiotherapeutic modalities. The WNTs comprise a large family of highly conserved growth factors associated with a number of functions. In this review, we focus largely on the canonical pathway, revealing the recent findings, in oral cancer research, thereby raising our understanding of the mechanisms of this crucial signaling in several cellular activities.