Protective effect of titanium tetrafluoride and silver diamine fluoride on radiation-induced dentin caries in vitro.

This in vitro study evaluated the protective effect of titanium tetrafluoride (TiF4) varnish and silver diamine fluoride (SDF) solution on the radiation-induced dentin caries. Bovine root dentin samples were irradiated (70 Gy) and treated as follows: (6 h): 4% TiF4 varnish; 5.42% NaF varnish; 30% SDF solution; placebo varnish; or untreated (negative control). Microcosm biofilm was produced from human dental biofilm (from patients with head-neck cancer) mixed with McBain saliva for the first 8 h. After 16 h and from day 2 to day 5, McBain saliva (0.2% sucrose) was replaced daily (37 °C, 5% CO2) (biological triplicate). Demineralization was quantified by transverse microradiography (TMR), while biofilm was analyzed by using viability, colony-forming units (CFU) counting and lactic acid production assays. The data were statistically analyzed by ANOVA (p < 0.05). TiF4 and SDF were able to reduce mineral loss compared to placebo and the negative control. TiF4 and SDF significantly reduced the biofilm viability compared to negative control. TiF4 significantly reduced the CFU count of total microorganism, while only SDF affected total streptococci and mutans streptococci counts. The varnishes induced a reduction in lactic acid production compared to the negative control. TiF4 and SDF may be good alternatives to control the development of radiation-induced dentin caries.

Anti-inflammatory effect of Arnica montana in a UVB radiation-induced skin-burn model in mice.

Background: ultraviolet radiation types A and B (UV) (400-315nm and 315-280nm respectively) are the main components present in sunlight known to cause skin injuries. Arnica montana is a plant that has been widely studied for containing anti-inflammatory, healing and analgesic properties capable of preventing or ameliorating lesions. Here, we investigated the therapeutic effect of topical application of Arnica montana after UVB-induced cutaneous injuries in mice.Methods: mice were exposed to UVB radiation (Philips TL40W/12 RS lamp) in a period of 3 hours. After one hour of radiation exposure, the animals were treated with topical application of Arnica montana ointment (250 mg/g) in the ear. At the time of 16 hours after treatment, the parameters of edema, oxidative stress and inflammatory reaction were measured in the ear of mice.Results: our results demonstrated that topical treatment with Arnica montana reduced the UVB-induced inflammatory response as demonstrated by the reduction of ear edema, inhibition of myeloperoxidase activation, decrease of nuclear factor kappa B levels and reduction of proinflammatory cytokines levels, such as interleukin-1beta, interleukin-6, tumour necrosis factor-alpha and interferon-gamma. In addition, Arnica montana ameliorated oxidative damage mediated by UVB radiation, as demonstrated by the reduction of lipid peroxidation, protein oxidation and increase of tissue antioxidant capacity and glutathione levels in the ear.Conclusion: we concluded that Arnica montana ointment is effective in alleviating the auricular inflammatory process and oxidative damage induced by acute UVB radiation, sustaining the traditional use of Arnica montana for the treatment of skin disorders.

Glucocorticoid and progesterone mechanisms in photoreceptor survival.

Death of retinal photoreceptors is the basis of prevalent blinding diseases. Since steroids might have a therapeutic role in retinal degenerations, we compared the protective effects of dexamethasone and progesterone on photoreceptor death induced by mifepristone and light exposure. Therefore, we studied the effective protection doses for each steroid in the two models. In addition, we analyzed changes in the levels of pro- and antiapoptotic molecules, glucocorticoid receptors α and ß (GRα and GRß), and rhodopsin under conditions of successful protection and photoreceptor survival. Mifepristone and light exposure selectively damaged photoreceptors. In light exposed retinas, photoreceptors mainly disappeared in the dorsotemporal region, while mifepristone produced a uniform damage. Dexamethasone and progesterone, at the same dose of 4 mg/kg/day for 2 days, preserved over 88% photoreceptor nuclei in both models. Assessment of cell death regulators showed that, in control retinas, both steroids activated BCL-XL, a prosurvival molecule, and decreased BID, a proapoptotic regulator. After steroid treatment of damaged retinas, BCL-XL, BCL2 and BAX showed characteristic patterns depending on the use of dexamethasone or progesterone on mifepristone or light exposed retinas. By contrast, BID decreased with any injury-steroid combination. Changes in GRα or GRß levels did not correlate with survival but were consistent with a mechanism of ligand induced downregulation of receptor expression. GRß might be upregulated by progesterone. Both dexamethasone and progesterone increased retinal rhodopsin stores, suggesting a link between photoreceptor protection and transduction pathways. Results show that dexamethasone and progesterone induced comparable but not identical protection responses in each model.

P1G10, the Proteolytic Fraction from Vasconcellea cundinamarcensis, Stimulates Tissue Repair after Acute Exposure to Ultraviolet B Radiation.

BACKGROUND: P1G10 is a cysteine proteolytic fraction from Vasconcellea cundinamarcensis latex, obtained by chromatographic separation on Sephadex-G10 and ultrafiltration. This fraction enhances healing in different models of skin lesions, and displays a protective/healing effect against gastric ulcers, where it was suggested an antioxidant role. METHODS: We evaluated here the effect of topical treatment with P1G10, in mice lesions induced by UVB. RESULTS: After single exposure to 2.4 J cm-2 UVB, P1G10 reduced erythema, increased cellularity of hypodermis, enhanced MPO activity and IL1ß, and inhibited COX2 levels. These results point to an anti-inflammatory effect by P1G10. This fraction displayed antioxidant activity by reversing the depletion of glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and reducing the catalase activity increased by UVB. These changes may be related to a reduction in MDA observed in groups treated with P1G10. P1G10 also inhibited MMP-9, caspase-3 and pkat while increasing p53 levels.

Inhibiting constitutive neurogenesis compromises long-term social recognition memory.

Although the functional role for newborn neurons in neural circuits is still matter of investigation, there is no doubt that neurogenesis modulates learning and memory in rodents. In general, boosting neurogenesis before learning, using genetic-target tools or drugs, improves hippocampus-dependent memories. However, inhibiting neurogenesis may yield contradictory results depending on the type of memory evaluated. Here we tested the hypothesis that inhibiting constitutive neurogenesis would compromise social recognition memory (SRM). Male Swiss mice were submitted to three distinct procedures to inhibit neurogenesis: (1) intra-cerebral infusion of Cystosine-ß-D-Arabinofuranoside (AraC); (2) intra-peritoneal injection of temozolomide (TMZ) and (3) cranial gamma irradiation. All three methods decreased cell proliferation and neurogenesis in the dentate gyrus of the dorsal (dDG) and ventral hippocampus (vDG), and the olfactory bulb (OB). However, the percentage inhibition diverged between methods and brain regions. Ara-C, TMZ and gamma irradiation impaired SRM, though only gamma irradiation did not cause side effects on weight gain, locomotor activity and anxiety. Finally, we examined the contribution of cell proliferation in vDG, dDG and OB to SRM. The percent of inhibition in the dDG correlates with SRM, independently of the method utilized. This correlation was observed for granular cell layer of OB and vDG, only when the inhibition was induced by gamma irradiation. Animal's performance was restrained by the inhibition of dDG cell proliferation, suggesting that cell proliferation in the dDG has a greater contribution to SRM. Altogether, our results demonstrate that SRM, similarly to other hippocampus-dependent memories, has its formation impaired by reducing constitutive neurogenesis.

Evaluation of prophylactic and therapeutic effects of sildenafil on acute radiation proctitis in rats.

PURPOSE: To investigate the prophylactic and therapeutical effects of sildenafil in a model of acute radiation proctitis (ARP). METHODS: All experimental procedures of this study was examined by histopathological, immunohistochemical and transmission electron microscopic analysis. RESULTS: Our histopathological evaluations indicated significant increases in lesion severity, cryptic apsis, cryptitis, cryptic distortion, reactive atypia and infiltration depth of the control (proctitis) group. While the prophylaxis group and the treatment group had significantly lower scores. High-dose group showed similar results as prophylaxis group. Histopathological findings of the prophylaxis group was more significant than the treatment group. Immunoreactivities of IL-1ß, FGF-2, TNF- α and HIF-1α increased in the control group especially in the epithelial and cryptic regions. On the contrary, sildenafil application caused significant decreases of inflammatory markers in all treatment groups, specifically better results in the prophylaxis group. CONCLUSION: The sildenafil has anti-inflammatory effects on ARP, as well as protective effects against ARP and the protective effect of sildenafil surpasses its therapeutic effect histopathologically.

Evaluation of prophylactic and therapeutic effects of sildenafil on acute radiation proctitis in rats

Abstract Purpose: To investigate the prophylactic and therapeutical effects of sildenafil in a model of acute radiation proctitis (ARP). Methods: All experimental procedures of this study was examined by histopathological, immunohistochemical and transmission electron microscopic analysis. Results: Our histopathological evaluations indicated significant increases in lesion severity, cryptic apsis, cryptitis, cryptic distortion, reactive atypia and infiltration depth of the control (proctitis) group. While the prophylaxis group and the treatment group had significantly lower scores. High-dose group showed similar results as prophylaxis group. Histopathological findings of the prophylaxis group was more significant than the treatment group. Immunoreactivities of IL-1β, FGF-2, TNF- α and HIF-1α increased in the control group especially in the epithelial and cryptic regions. On the contrary, sildenafil application caused significant decreases of inflammatory markers in all treatment groups, specifically better results in the prophylaxis group. Conclusion: The sildenafil has anti-inflammatory effects on ARP, as well as protective effects against ARP and the protective effect of sildenafil surpasses its therapeutic effect histopathologically.

Anti-inflammatory effects of hyperbaric oxygen on irradiated laryngeal tissues / Efeitos anti-inflamatórios do oxigênio hiperbárico sobre tecidos laríngeos irradiados

Abstract Introduction To manage the complications of irradiation of head and neck tissue is a challenging issue for the otolaryngologist. Definitive treatment of these complications is still controversial. Recently, hyperbaric oxygen therapy is promising option for these complications. Objective In this study, we used biochemical and histopathological methods to investigate the efficacy of hyperbaric oxygen against the inflammatory effects of radiotherapy in blood and laryngeal tissues when radiotherapy and hyperbaric oxygen are administered on the same day. Methods Thirty-two Wistar Albino rats were divided into four groups. The control group was given no treatment, the hyperbaric oxygen group was given only hyperbaric oxygen therapy, the radiotherapy group was given only radiotherapy, and the radiotherapy plus hyperbaric oxygen group was given both treatments on the same day. Results Histopathological and biochemical evaluations of specimens were performed. Serum tumor necrosis factor-α, interleukin-1β, and tissue inflammation levels were significantly higher in the radiotherapy group than in the radiotherapy plus hyperbaric oxygen group, whereas interleukin-10 was higher in the radiotherapy plus hyperbaric oxygen group. Conclusion When radiotherapy and hyperbaric oxygen are administered on the same day, inflammatory cytokines and tissue inflammation can be reduced in an early period of radiation injury.

Resumo Introdução O manejo das complicações da irradiação do tecido da cabeça e pescoço é uma questão desafiadora para o otorrinolaringologista. O tratamento definitivo dessas complicações ainda é controverso. Recentemente, a oxigenoterapia hiperbárica tem sido uma opção promissora para essas complicações. Objetivo Nesse estudo foram usados métodos bioquímicos e histopatológicos para investigar a eficácia do oxigênio hiperbárico contra os efeitos inflamatórios da radioterapia no sangue e nos tecidos laríngeos, quando a radioterapia e oxigênio hiperbárico são administrados no mesmo dia. Métodos Trinta e dois ratos Wistar albinos foram divididos em quatro grupos. O grupo controle nao recebeu tratamento, o grupo de oxigenio hiperbarico recebeu apenas oxigenoterapia hiperbarica, o grupo de radioterapia recebeu apenas radioterapia e o grupo de radioterapia com oxigenio hiperbarico recebeu ambos os tratamentos no mesmo dia. Resultados Foram realizadas avaliaçoes histopatologicas e bioquimicas dos especimes. Os niveis sericos de fator de necrose tumoral-α, interleucina-1β e inflamaçao tecidual foram significativamente maiores no grupo de radioterapia do que no grupo de radioterapia mais oxigenio hiperbarico, enquanto que a interleucina-10 foi maior no grupo de radioterapia mais oxigenio hiperbarico. Conclusão Quando a radioterapia e o oxigênio hiperbárico são administrados no mesmo dia, as citocinas inflamatórias e a inflamação tecidual podem ser reduzidas no período inicial da radiação.

Therapeutic effect of Aloe vera and silver nanoparticles on acid-induced oral ulcer in gamma-irradiated mice.

Radiation combined injury, a life-threatening condition, has higher mortality than simple radiation injury. The aim of the present study was to analyze the efficiency of Aloe vera and silver nanoparticles in improving the healing of ulcerated oral mucosa after irradiation. Thirty male Albino mice were divided into five groups: control, radiation, Aloe vera (AV), silver nanoparticles (NS), and AV+NS. The mice were exposed to whole body 6Gy gamma-radiation. After one hour, 20% acetic acid was injected into the submucosal layer of the lower lip for ulcer induction. The animals received topical treatment with the assigned substances for 5 days. Lip specimens were subjected to hematoxylin and eosin and anti alpha-smooth muscle actin immunohistochemical staining. Results demonstrated occurance of ulcer three days post irradiation in all groups except in the AV+NS group where only epithelial detachment was developed. After seven days, data revealed persistent ulcer in radiation group, and almost normal epithelium in the AV+NS group. A significant reduction of epithelial thickness was detected in all groups at the third day as compared to control. At the seventh day, only the AV+NS group restored the epithelial thickness. Area percent of alpha-smooth muscle actin expression was significantly decreased in radiation group at the third day followed by significant increase at the seventh day. However, all treatment groups showed significant increase in alpha-smooth muscle actin at the third day, which decreased to normal level at the seventh day. Our study demonstrated the efficiency of Aloe vera and silver nanoparticles in enhancing ulcer healing after irradiation.

Effect of Alendronate on Bone Microarchitecture in Irradiated Rats With Osteoporosis: Micro-CT and Histomorphometric Analysis.

PURPOSE: The aim of the present study was to evaluate the effect of alendronate (ALN) on the bone microarchitecture of irradiated rats with estrogen deficiency, using microcomputed tomography (micro-CT) and histomorphometric analysis. MATERIALS AND METHODS: Forty adult Wistar rats were subjected to ovariectomy and randomly divided into the following groups: control (CON), ALN, irradiated (IRR), and ALN/irradiated (ALN/IRR). Approximately 50 days after ovariectomy, the hind limbs of the rats in the IRR and ALN/IRR groups were irradiated with 15 Gy of x-radiation. The rats were euthanized 7 and 30 days after irradiation. The bone microarchitecture was analyzed using micro-CT and histomorphometry. The bone microarchitecture was evaluated using the Mann-Whitney U test, analysis of variance, and the post hoc Tukey test, with statistical significance set at 5%. RESULTS: Irradiation had increased the thickness of the cortical bone at 7 days (P < .05) and also decreased the number of trabeculae per unit length and increased the average distance between the trabeculae (P < .05) at 30 days. ALN inhibited the deleterious effect of x-radiation, preventing the distance between the trabeculae from increasing and the number of trabeculae per unit length from decreasing (P < .05). CONCLUSIONS: The present results have demonstrated that the initial effect of ALN could be positive, because it checked the deleterious action in the bone tissue submitted to x-radiation.

Anti-inflammatory effects of hyperbaric oxygen on irradiated laryngeal tissues.

INTRODUCTION: To manage the complications of irradiation of head and neck tissue is a challenging issue for the otolaryngologist. Definitive treatment of these complications is still controversial. Recently, hyperbaric oxygen therapy is promising option for these complications. OBJECTIVE: In this study, we used biochemical and histopathological methods to investigate the efficacy of hyperbaric oxygen against the inflammatory effects of radiotherapy in blood and laryngeal tissues when radiotherapy and hyperbaric oxygen are administered on the same day. METHODS: Thirty-two Wistar Albino rats were divided into four groups. The control group was given no treatment, the hyperbaric oxygen group was given only hyperbaric oxygen therapy, the radiotherapy group was given only radiotherapy, and the radiotherapy plus hyperbaric oxygen group was given both treatments on the same day. RESULTS: Histopathological and biochemical evaluations of specimens were performed. Serum tumor necrosis factor-α, interleukin-1ß, and tissue inflammation levels were significantly higher in the radiotherapy group than in the radiotherapy plus hyperbaric oxygen group, whereas interleukin-10 was higher in the radiotherapy plus hyperbaric oxygen group. CONCLUSION: When radiotherapy and hyperbaric oxygen are administered on the same day, inflammatory cytokines and tissue inflammation can be reduced in an early period of radiation injury.

Therapeutic effect of Aloe vera and silver nanoparticles on acid-induced oral ulcer in gamma-irradiated mice

Abstract Radiation combined injury, a life-threatening condition, has higher mortality than simple radiation injury. The aim of the present study was to analyze the efficiency of Aloe vera and silver nanoparticles in improving the healing of ulcerated oral mucosa after irradiation. Thirty male Albino mice were divided into five groups: control, radiation, Aloe vera (AV), silver nanoparticles (NS), and AV+NS. The mice were exposed to whole body 6Gy gamma-radiation. After one hour, 20% acetic acid was injected into the submucosal layer of the lower lip for ulcer induction. The animals received topical treatment with the assigned substances for 5 days. Lip specimens were subjected to hematoxylin and eosin and anti alpha-smooth muscle actin immunohistochemical staining. Results demonstrated occurance of ulcer three days post irradiation in all groups except in the AV+NS group where only epithelial detachment was developed. After seven days, data revealed persistent ulcer in radiation group, and almost normal epithelium in the AV+NS group. A significant reduction of epithelial thickness was detected in all groups at the third day as compared to control. At the seventh day, only the AV+NS group restored the epithelial thickness. Area percent of alpha-smooth muscle actin expression was significantly decreased in radiation group at the third day followed by significant increase at the seventh day. However, all treatment groups showed significant increase in alpha-smooth muscle actin at the third day, which decreased to normal level at the seventh day. Our study demonstrated the efficiency of Aloe vera and silver nanoparticles in enhancing ulcer healing after irradiation.

Hangeshashinto (TJ-14) prevents radiation-induced mucositis by suppressing cyclooxygenase-2 expression and chemotaxis of inflammatory cells.

PURPOSE: Radiation-induced oral mucositis is the most common side effect of radiotherapy in head and neck cancer; however, effective modalities for its prevention have not been established. In this study, we evaluated the effectiveness of Hangeshashinto (TJ-14), a Japanese herbal medicine, for preventing radiation-induced mucositis and elucidated its effect on inflammatory responses, including inflammatory cell chemotaxis and cyclooxygenase-2 (COX2) expression, in an animal model. METHODS: Syrian hamsters, 8-9 weeks old, were enrolled in this study. Animals were irradiated with a single 40 Gy dose to the buccal mucosa. Hamsters freely received a treatment diet mixed with 2% TJ-14 or a normal diet daily. The therapeutic effect was determined based on the visual mucositis score, body weight, and histological examination of infiltrated neutrophils and COX2 expression. RESULTS: TJ-14 significantly reduced the severity of mucositis. The percentage with severe mucositis (score ≥3) was 100% in the untreated group and 16.7% in the TJ-14 group (P < 0.05). There was no difference in body weight change between the groups; however, weight gain in the untreated group tended to be suppressed compared to that in the TJ-14 group during the peak period of mucositis. In addition, TJ-14 inhibited the infiltration of neutrophils and COX2 expression in irradiated mucosa (P < 0.05). CONCLUSIONS: TJ-14 reduced the severity of mucositis in an animal model by suppressing the inflammatory response. Because TJ-14 is inexpensive and its safety is established, it is a promising candidate for the standard treatment of radiation-induced mucositis in cancer patients.

Development of a new model of actinic enteritis in rats using a cobalt-60 open source and a protection device as a collimator.

PURPOSE:: To describe a new model of actinic enteritis that does not use radiotherapy machines. METHODS:: Sixteen Wistar rats were divided into four groups, consisting of four animals each: control (group A), two weeks after irradiation (group B), five weeks after irradiation (group C) and eight weeks after irradiation (group D). Animals were given a 10Gy radiation from a Cobalt-60 natural source in a nuclear technology research center. Protections of the surrounding tissues were obtained through the usage of plumb devices with a hole in the center, which served as a collimator. We obtained irradiated and non-irradiated colons from each animal. RESULTS:: In group B we found an important inflammatory response in the irradiated colon, which appeared in a reduced way in group C and was minimal in group D, in which we found a relevant collagen submucosal deposition/fibrosis. In all groups, the non-irradiated colon had a lower pathological damage in comparison with the irradiated colon. CONCLUSION:: We thus described an efficient and feasible technique for obtaining an animal model of actinic enteritis.

Complement C5a receptor knockout has diminished light-induced microglia/macrophage retinal migration.

PURPOSE: The complement system is involved in the pathogenesis of age-related macular degeneration (AMD). Because activated microglia are also associated with AMD, we studied the relationship between complement anaphylatoxin receptors and microglial recruitment. METHODS: We assessed the effect of anaphylatoxin C3a receptor (C3aR) and C5a receptor (C5aR) knockout (KO) on light damage-induced migration of microglia/macrophages into the mouse outer retina via immunofluorescence and real-time quantitative PCR. RESULTS: We found that the mRNA levels of C3, C5, C3aR, C5aR, and two activators of the complement alternative pathway, Cfb and Cfd, were all upregulated after light exposure. Retinal Iba1-positive microglia/macrophages express receptors for C3a and C5a. Light damage increased the number of retinal Iba1-positive cells and the mRNA levels of Iba1. Compared with the wild-type (WT) mice, these increases were attenuated in the C5aR KO mice but not in the C3aR KO mice. CONCLUSIONS: C5aR but not C3aR promoted the recruitment of microglia/macrophages. These divergent properties of complement anaphylatoxins in the light damage model provide a rationale for testing the differential effects of these receptors in additional retinal and neurodegeneration models.

Short- and long-term effects of zinc treatment on lacrimal gland histopathology and tear functions tests in radioiodine-administered rats.

PURPOSE:: To investigate the short-term (1 week) and long-term (8 weeks) protective effects of zinc administration on radioiodine (RAI)-induced lacrimal gland damage of rats. METHODS:: A total of 40 rats were divided into two groups: an RAI group (n=20), which was administrated a single dose of 3 mCi of 131I and 1 mL physiologic saline for 7 days by gastric gavage, and a zinc group (n=20), which received a single dose of 3 mCi of 131I and 1 mL of physiologic saline containing zinc sulfate at a concentration of 10 mg/kg concentration for 7 days by gastric gavage. All rats underwent tear function tests before and 1 week after RAI administration. About 1 week after irradiation, half of the animals in each group were sacrificed and the extraorbital lacrimal glands were removed for histopathological examination. The remaining animals of the groups underwent the same procedures at 8 weeks after irradiation. RESULTS:: In the RAI and zinc groups, the mean tear production was 3.75 ± 1.55 and 3.65 ± 1.53 mm at baseline, 2.10 ± 1.07 and 3.30 ± 1.34 mm at week 1 (p=0.004), and 3.22 ± 1.48 and 3.50 ± 1.78 mm at week 8, respectively; further, the mean corneal fluorescein staining scores were 4.65 ± 2.16 and 4.80 ± 2.21 points at baseline, 7.85 ± 1.90 and 5.45 ± 2.06 points at week 1 (p=0.001), and 5.44 ± 2.13 and 4.90 ± 2.08 at week 8, respectively. The histopathological changes in rat lacrimal glands at weeks 1 and 8 were consistent with the tear function test results. CONCLUSIONS:: Zinc treatment seems to be protective against RAI-induced lacrimal gland damage of rats, particularly in the acute period.

Development of a new model of actinic enteritis in rats using a cobalt-60 open source and a protection device as a collimator

Abstract Purpose: To describe a new model of actinic enteritis that does not use radiotherapy machines. Methods: Sixteen Wistar rats were divided into four groups, consisting of four animals each: control (group A), two weeks after irradiation (group B), five weeks after irradiation (group C) and eight weeks after irradiation (group D). Animals were given a 10Gy radiation from a Cobalt-60 natural source in a nuclear technology research center. Protections of the surrounding tissues were obtained through the usage of plumb devices with a hole in the center, which served as a collimator. We obtained irradiated and non-irradiated colons from each animal. Results: In group B we found an important inflammatory response in the irradiated colon, which appeared in a reduced way in group C and was minimal in group D, in which we found a relevant collagen submucosal deposition/fibrosis. In all groups, the non-irradiated colon had a lower pathological damage in comparison with the irradiated colon. Conclusion: We thus described an efficient and feasible technique for obtaining an animal model of actinic enteritis.

Short- and long-term effects of zinc treatment on lacrimal gland histopathology and tear functions tests in radioiodine-administered rats / Efeitos de curto e longo prazo do tratamento com zinco na histopatologia da glândula lacrimal e funções lacrimais em ratos que receberam iodo radioativo

ABSTRACT Purpose: To investigate the short-term (1 week) and long-term (8 weeks) protective effects of zinc administration on radioiodine (RAI)-induced lacrimal gland damage of rats. Methods: A total of 40 rats were divided into two groups: an RAI group (n=20), which was administrated a single dose of 3 mCi of 131I and 1 mL physiologic saline for 7 days by gastric gavage, and a zinc group (n=20), which received a single dose of 3 mCi of 131I and 1 mL of physiologic saline containing zinc sulfate at a concentration of 10 mg/kg concentration for 7 days by gastric gavage. All rats underwent tear function tests before and 1 week after RAI administration. About 1 week after irradiation, half of the animals in each group were sacrificed and the extraorbital lacrimal glands were removed for histopathological examination. The remaining animals of the groups underwent the same procedures at 8 weeks after irradiation. Results: In the RAI and zinc groups, the mean tear production was 3.75 ± 1.55 and 3.65 ± 1.53 mm at baseline, 2.10 ± 1.07 and 3.30 ± 1.34 mm at week 1 (p=0.004), and 3.22 ± 1.48 and 3.50 ± 1.78 mm at week 8, respectively; further, the mean corneal fluorescein staining scores were 4.65 ± 2.16 and 4.80 ± 2.21 points at baseline, 7.85 ± 1.90 and 5.45 ± 2.06 points at week 1 (p=0.001), and 5.44 ± 2.13 and 4.90 ± 2.08 at week 8, respectively. The histopathological changes in rat lacrimal glands at weeks 1 and 8 were consistent with the tear function test results. Conclusions: Zinc treatment seems to be protective against RAI-induced lacrimal gland damage of rats, particularly in the acute period.

RESUMO Objetivo: Investigar se o tratamento com zinco tem efeito protetor, no curto prazo (1 semana) e longo prazo (8 semanas), sobre os danos induzidos na glândula lacrimal por iodo radiotativo (RAI) em ratos. Métodos: Quarenta ratos foram divididos em dois grupos. No grupo RAI (n=20) foi administrada uma única dose de 3 mCi 131I e 1 cc de solução salina fisiológica durante 7 dias, por gavagem gástrica. O grupo zinco (n=20) recebeu uma dose única de 3 mCi 131I e 1 cc de solução salina fisiológica contendo sulfato de zinco na concentração de 10 mg/kg durante 7 dias por gavagem gástrica. Os testes de função lacrimal foram realizadas para todos os animais antes e após uma semana da administração da RAI. Em seguida, após 1 semana da administração, metade dos animais de cada grupo foi sacrificada e as glândulas lacrimais extraorbitais foram removidas para exame histopatológico. Os animais remanescentes dos grupos foram submetidos aos mesmos procedimentos após 8 semanas a radiação. Resultados: As médias de produção lacrimal foram de 3,75 ± 1,55 e 3,65 ± 1,53 mm na linha de base, 2,10 ± 1,07 e 3,30 ± 1,34 mm na 1a semana (p=0,004), e 3,22 ± 1,48 e 3,50 ± 1,78 mm na 8a semana, para os grupos RAI e zinco, respectivamente. As pontuações médias de coloração fluoresceína foram 4,65 ± 2,16 e 4,80 ± 2,21 no início do estudo, 7,85 ± 1,90 e 5,45 ± 2,06 na primeira semana (p=0,001), 5,44 ± 2,13 e 4,90 ± 2,08 pontos na 8a semana, para os grupos RAI e zinco, respectivamente. As alterações histopatológicas das glândulas lacrimais em 1 e 8 semanas foram consistentes com os testes de função lacrimal resultados. Conclusões: O tratamento de zinco parece ser protetor sobre os danos glândula lacrimal induzidos por RAI em ratos, especialmente no período agudo.

L-carnitine has a protective effect on the colonic mucosa during abdominopelvic radiotherapy in rats.

PURPOSE:: To evaluate histopathologically the radioprotective effect of L-carnitine on the colonic mucosa in rats undergoing abdominopelvic irradiation. METHODS:: Thirty-two rats were randomly assigned to four experimental groups: intraperitoneal administration of normal saline (group 1) or L-carnitine (300 mL/kg; group 2), followed in groups 3 and 4, respectively, by one dose of abdominopelvic radiation (20 Gy) 30 min later. Rats were sacrificed 5 days after radiation, and their descending colons were resected for histopathological evaluation of the presence and severity of damage. RESULTS:: Average damage scores did not differ significantly between groups 1 and 2 (0.13 ± 0.35 and 0.25 ± 0.46, respectively); the group 3 score was highest (10.25 ± 0.71), and the group 4 score (3.63 ± 1.41) was significantly lower than that of group 3 (both p = 0.0001). Pre-radiation L-carnitine administration significantly reduced mucosal thinning, crypt distortion, reactive atypia, inflammation, cryptitis, and reactive lymph-node hyperplasia (all p < 0.01). CONCLUSIONS:: L-carnitine had a radioprotective effect on rat colonic mucosa. L-carnitine use should be explored for patients with gastrointestinal cancer, who have reduced serum L-carnitine levels.