Effect of melatonin on antioxidant capacity, inflammation and apoptotic cell death in lung tissue of diabetic rats

Purpose: To investigate the effects of melatonin on antioxidant capacity, inflammation and apoptotic cell death (through expression of cleaved-caspase 3) in lung tissue samples of diabetic rats. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control group) was made up of healthy rats. Group 2 (diabetes group) received streptozotocin at a dose of 50 mg/kg/day for 5 days.Group 3 (diabetes plus melatonin group) received streptozotocin at a dose of 50 mg/kg/day for 5 days and then they received melatonin at a dose of 20 mg/kg/day between 28th and 35th days of the study. Results: Tissue MDA and MPO levels were found to be significantly higher in diabetes group compared to control group (p< 0.05) whilst administration of melatonin was found to significantly lower this increase down to normal levels (p <0.05). Bronchus associated lymphoid tissue (BALT) was more severe in diabetics whereas administration of melatonin alleviated this hyperplasia. Cleaved caspase 3 activity was severe in hyperplastic BALT in diabetic rats however in lowered down to moderate level when melatonin was administered. Conclusion: The melatonin caused an increase in antioxidant capacity and decreased the expression of cleaved-caspase 3.(AU)

Wound healing of diabetic rats treated with Moringa oleifera extract

Purpose: To evaluate if Moringa oleifera leaf aqueous extract (ME) influences the healing of skin wounds of diabetic rats. Methods: Wistar rats were used (6 rats/group). Group 1 received normal saline (NS) v.o. Group 2 received moringa extract (100mg/kg v.o) for 3 weeks. Groups 3 and 4: Streptozotocin (STZ) induced diabetes. Group 3 received NS; Group 4 received aqueous ME (100mg/kg) v.o.The wounds of groups 1 and 3 rats were topically treated with NS; wounds of groups 2 and 4 treated with 200µL of 10% ME. After anesthesia, all rats had skin square excision wounds 1.5cm2. Wound percent contractions were measured. On 10th day, blood glucose and serum cytokines were measured. Histometry of wounds was studied using ImagePro6.0 software. Results: Glycemia was significantly reduced in ME treated rats. These rats had higher percent contraction of the wounds on 2nd, 5th and 10th days, then controls (p<0.05). Diabetic rats treated with NS had TNF-α, IL-1β and IL-6 expression higher than in rats receiving ME. The histopathological score of ME treated diabetic rats (198±13.7) was significantly higher than treatment with NS (145±10.5). Conclusion: ME extract positively influenced healing of wounds in diabetic rats after systemic and topical treatment.(AU)

Evaluation of programmed cell death processes on the lens epithelium of older dogs with diabetic and hypermature cataracts / Avaliação dos processos de morte celular programada no epitélio da lente de cães idosos com catarata diabética e hipermadura

It is well known that posterior capsule opacification (PCO), one of the most common late postoperative complications of cataract surgery, is mainly caused by proliferation and differentiation of remaining lens epithelial cells (LECs) on the posterior lens capsule. Many authors suggest that alterations induced by the pathophysiology of cataracts, its metabolism and the use of 0.1% trypan blue (TB) must cause some degree of cellular damage on these cells, wicht would help to prevent and/or reduce the incidence of PCO after cataract surgery in humans. Therefore, the aim of this study was to evaluate the expression of cell death markers on LECs of older dogs with diabetic and hypermature cataracts, after capsulorhexis, both using 0.1% TB. Twenty samples collected from 13 dogs of different breeds, with ages varying from 8 to 12 years-old, with diabetic and hypermature cataracts, which had been subjected to phacoemulsification surgery (Phaco) using 0.1% TB for staining were studied. Animals were classified as dogs with diabetic (DC) and hypermature cataracts (HC), and expression of molecular markers for apoptosis and autophagy (caspase-3 and beclin-1) on LECs were obtained by immunofluorescence technique. The expression of caspase-3 and beclin-1 was observed in every studied sample and did not differ between groups. In conclusion, our findings suggest that apoptosis and autophagy processes occur to LECs in older dogs presenting diabetic and hypermature cataracts after Phaco utilizing 0.1% TB. Our results may be helpful to future studies of PCO in post-phacoemulsification surgery patients.(AU)

A opacificação da cápsula posterior da lente do globo ocular é a complicação mais observada após a remoção da lente. Essa patologia é causada principalmente pela proliferação e diferenciação das células do epitélio anterior da lente em sua cápsula posterior. Muitos autores sugerem que alterações induzidas pelo metabolismo e/ou patofisiologia da catarata e o uso do corante de azul de tripan a 0,1% devam causar algum dano a essas células, o que supostamente ajudaria a prevenir e reduzir a incidência de tal complicação em humanos. Este trabalho avaliou a expressão de marcadores de morte celular no epitélio anterior da lente de cães idosos com catarata diabética e hipermadura, após capsulorrexe realizada com o emprego do azul de tripan a 0,1%. Foram estudadas vinte amostras colhidas de treze cães de diferentes raças, com idades variando de oito a doze anos, que apresentavam catarata diabética ou hipermadura e que foram submetidos à facoemulsificação utilizando corante de azul de tripan a 0,1%. Foram designados dois grupos: com catarata diabética (DC) e com catarata hipermadura (HC). A expressão molecular dos marcadores de morte celular por apoptose a autofagia (caspase-3 e beclina-1) no epitélio anterior da lente foi avaliada pela técnica de imunofluorescência. Observou-se que a expressão de caspase-3 e beclina-1 ocorreu em todas as amostras e não foi diferente entre os grupos. Os achados deste estudo sugerem que o processo de morte celular por apoptose e autofagia ocorre no epitélio anterior da lente de cães idosos com catarata diabética e hipermadura submetidos à facoemulsificação com o corante de azul de tripan a 0,1%. Este resultado pode ser útil para estudos futuros da opacidade da cápsula posterior da lente em cães submetidos à facoemulsificação.(AU)

Evaluation of programmed cell death processes on the lens epithelium of older dogs with diabetic and hypermature cataracts / Avaliação dos processos de morte celular programada no epitélio da lente de cães idosos com catarata diabética e hipermadura

It is well known that posterior capsule opacification (PCO), one of the most common late postoperative complications of cataract surgery, is mainly caused by proliferation and differentiation of remaining lens epithelial cells (LECs) on the posterior lens capsule. Many authors suggest that alterations induced by the pathophysiology of cataracts, its metabolism and the use of 0.1% trypan blue (TB) must cause some degree of cellular damage on these cells, wicht would help to prevent and/or reduce the incidence of PCO after cataract surgery in humans. Therefore, the aim of this study was to evaluate the expression of cell death markers on LECs of older dogs with diabetic and hypermature cataracts, after capsulorhexis, both using 0.1% TB. Twenty samples collected from 13 dogs of different breeds, with ages varying from 8 to 12 years-old, with diabetic and hypermature cataracts, which had been subjected to phacoemulsification surgery (Phaco) using 0.1% TB for staining were studied. Animals were classified as dogs with diabetic (DC) and hypermature cataracts (HC), and expression of molecular markers for apoptosis and autophagy (caspase-3 and beclin-1) on LECs were obtained by immunofluorescence technique. The expression of caspase-3 and beclin-1 was observed in every studied sample and did not differ between groups. In conclusion, our findings suggest that apoptosis and autophagy processes occur to LECs in older dogs presenting diabetic and hypermature cataracts after Phaco utilizing 0.1% TB. Our results may be helpful to future studies of PCO in post-phacoemulsification surgery patients.(AU)

A opacificação da cápsula posterior da lente do globo ocular é a complicação mais observada após a remoção da lente. Essa patologia é causada principalmente pela proliferação e diferenciação das células do epitélio anterior da lente em sua cápsula posterior. Muitos autores sugerem que alterações induzidas pelo metabolismo e/ou patofisiologia da catarata e o uso do corante de azul de tripan a 0,1% devam causar algum dano a essas células, o que supostamente ajudaria a prevenir e reduzir a incidência de tal complicação em humanos. Este trabalho avaliou a expressão de marcadores de morte celular no epitélio anterior da lente de cães idosos com catarata diabética e hipermadura, após capsulorrexe realizada com o emprego do azul de tripan a 0,1%. Foram estudadas vinte amostras colhidas de treze cães de diferentes raças, com idades variando de oito a doze anos, que apresentavam catarata diabética ou hipermadura e que foram submetidos à facoemulsificação utilizando corante de azul de tripan a 0,1%. Foram designados dois grupos: com catarata diabética (DC) e com catarata hipermadura (HC). A expressão molecular dos marcadores de morte celular por apoptose a autofagia (caspase-3 e beclina-1) no epitélio anterior da lente foi avaliada pela técnica de imunofluorescência. Observou-se que a expressão de caspase-3 e beclina-1 ocorreu em todas as amostras e não foi diferente entre os grupos. Os achados deste estudo sugerem que o processo de morte celular por apoptose e autofagia ocorre no epitélio anterior da lente de cães idosos com catarata diabética e hipermadura submetidos à facoemulsificação com o corante de azul de tripan a 0,1%. Este resultado pode ser útil para estudos futuros da opacidade da cápsula posterior da lente em cães submetidos à facoemulsificação.(AU)

A curcumin derivative J147 ameliorates diabetic peripheral neuropathy in streptozotocin (STZ)-induced DPN rat models through negative regulation AMPK on TRPA1

Purpose: To investigate the specific molecular mechanisms and effects of curcumin derivative J147 on diabetic peripheral neuropathy (DPN). Methods: We constructed streptozotocin (STZ)-induced DPN rat models to detected mechanical withdrawal threshold (MWT) in vivo using Von Frey filaments. In vitro, we measured cell viability and apoptosis, adenosine 5-monophosphate-activated protein kinase (AMPK) and transient receptor potential A1 (TRPA1) expression using MTT, flow cytometry, qRT-PCR and western blot. Then, TRPA1 expression level and calcium reaction level were assessed in agonist AICAR treated RSC96cells. Results: The results showed that J147reduced MWT in vivo, increased the mRNA and protein level of AMPK, reduced TRPA1 expression and calcium reaction level in AITCR treated RSC96 cells, and had no obvious effect on cell viability and apoptosis. Besides, AMPK negative regulated TRPA1 expression in RSC96 cells. Conclusions: J147 could ameliorate DPN via negative regulation AMPK on TRPA1 in vivo and in vitro. A curcumin derivative J147might be a new therapeutic potential for the treatment of DPN.(AU)

Retina assessment by optical coherence tomography of diabetic dogs / Avaliação da retina de cães diabéticos pela tomografia de coerência óptica

Diabetes mellitus is one of the most common endocrine disorders characterized by relative or absolute lack of insulin; this can lead to several ocular manifestations, among them diabetic retinopathy and cataracts. Diabetic retinopathy (DR) is a microangiopathy that involves retinal precapillary arterioles, postcapillary venules, and large vessels, causing them to be functionally and anatomically incompetent. Hyperglycemia seems to be the most probable cause of damage to the retina due to interference in cellular metabolism and transduction processes. The aim of this study was to evaluate retinal thickness in eight diabetic dogs, four females and four males of different breeds and ages ranging from 6 to 15 years, by optical coherence tomography (OCT) and to compare them with non-diabetic dogs. Assessment provided by OCT in diabetic dogs showed retinal layers thinning and loss of stratification when compared to non-diabetic dogs (198μm versus 219μm respectively), with statistical significance (p=0.008). OCT images may suggest that diabetes mellitus causes retinal neuropathy in dogs, as also seen in diabetic humans.(AU)

Diabete melito é umas das principais endocrinopatias, caracterizada pela deficiência relativa ou absoluta de insulina, que pode resultar em diversas manifestações oculares, sendo as mais frequentes a retinopatia diabética e a catarata. Retinopatia diabética (RD) é uma microangiopatia que afeta primeiramente as arteríolas pré-capilares, capilares, vênulas pós-capilares e vasos de maior calibre, causando incompetência funcional e anatômica dos vasos retinianos. A hiperglicemia parece ser a causa mais provável da lesão retiniana, interferindo nas vias de metabolismo celular e no processo de transdução. Objetivou-se neste estudo avaliar e comparar a espessura retiniana total em oito cães diabéticos, quatro fêmeas e quatro machos, de diversas raças, com idade variando de seis a 15 anos, com auxílio de tomografia de coerência óptica (OCT) e comparar com a de cães não diabéticos. A espessura e arquitetura retiniana realizada pela OCT nos cães diabéticos, demonstrou afinamento das camadas da retina e perda da estratificação em comparação com os cães não diabéticos (198μm versus 219μm, respectivamente), sendo esta redução estatisticamente significante (p=0,008). Baseado nas imagens da OCT pode-se sugerir que a diabete melito, no cão, cause neuropatia retiniana como descrito em humanos diabéticos.(AU)

Retina assessment by optical coherence tomography of diabetic dogs / Avaliação da retina de cães diabéticos pela tomografia de coerência óptica

Diabetes mellitus is one of the most common endocrine disorders characterized by relative or absolute lack of insulin; this can lead to several ocular manifestations, among them diabetic retinopathy and cataracts. Diabetic retinopathy (DR) is a microangiopathy that involves retinal precapillary arterioles, postcapillary venules, and large vessels, causing them to be functionally and anatomically incompetent. Hyperglycemia seems to be the most probable cause of damage to the retina due to interference in cellular metabolism and transduction processes. The aim of this study was to evaluate retinal thickness in eight diabetic dogs, four females and four males of different breeds and ages ranging from 6 to 15 years, by optical coherence tomography (OCT) and to compare them with non-diabetic dogs. Assessment provided by OCT in diabetic dogs showed retinal layers thinning and loss of stratification when compared to non-diabetic dogs (198μm versus 219μm respectively), with statistical significance (p=0.008). OCT images may suggest that diabetes mellitus causes retinal neuropathy in dogs, as also seen in diabetic humans.(AU)

Diabete melito é umas das principais endocrinopatias, caracterizada pela deficiência relativa ou absoluta de insulina, que pode resultar em diversas manifestações oculares, sendo as mais frequentes a retinopatia diabética e a catarata. Retinopatia diabética (RD) é uma microangiopatia que afeta primeiramente as arteríolas pré-capilares, capilares, vênulas pós-capilares e vasos de maior calibre, causando incompetência funcional e anatômica dos vasos retinianos. A hiperglicemia parece ser a causa mais provável da lesão retiniana, interferindo nas vias de metabolismo celular e no processo de transdução. Objetivou-se neste estudo avaliar e comparar a espessura retiniana total em oito cães diabéticos, quatro fêmeas e quatro machos, de diversas raças, com idade variando de seis a 15 anos, com auxílio de tomografia de coerência óptica (OCT) e comparar com a de cães não diabéticos. A espessura e arquitetura retiniana realizada pela OCT nos cães diabéticos, demonstrou afinamento das camadas da retina e perda da estratificação em comparação com os cães não diabéticos (198μm versus 219μm, respectivamente), sendo esta redução estatisticamente significante (p=0,008). Baseado nas imagens da OCT pode-se sugerir que a diabete melito, no cão, cause neuropatia retiniana como descrito em humanos diabéticos.(AU)

Antibacterial activity of 3, 3', 4'-Trihydroxyflavone from Justicia wynaadensis against diabetic wound and urinary tract infection

The present investigation was designed to study the effect of an active compound isolated from Justicia wynaadensis against multi drug resistant organisms (MDRO's) associated with diabetic patients. The drug resistant pathogens implicated in wound and urinary tract infection of diabetic patients were isolated and identified by molecular sequencing. Solvent-solvent fractionation of crude methanol extract produced hexane, chloroform, ethyl acetate and methanol-water fraction, among which chloroform fraction was found to be potent when compared with other three fractions. Further, chloroform fraction was subjected to preparatory HPLC (High-Performance Liquid Chromatography), that produced four sub-fractions; chloroform HPLC fraction 1 (CHF1) through CHF4. Among the sub-fractions, CHF1 inhibited the pathogens effectively in comparison to other three sub-fractions. The purity of CHF1 was found to be >95%. Therefore, CHF1 was further characterized by NMR and FTIR analysis and based on the structure elucidated, the compound was found to be 3,3',4'-Trihydroxyflavone. The effective dose of this bioactive compound ranged from 32 µg/mL to 1.2 mg/mL. Thus, the present study shows that 3,3',4'-Trihydroxyflavone isolated from J. wynaadensis is an interesting biopharmaceutical agent and could be considered as a source of antimicrobial agent for the treatment of various infections and used as a template molecule for future drug development.(AU)

Exogenous neuregulin-1 attenuates STZ-induced diabetic peripheral neuropathic pain in rats

Purpose: To investigate whether modulating NRG1 could attenuate diabetic neuropathic pain and analyze the underlying mechanism. Methods: Male SD rats were randomly divided into control group, diabetic group, NRG1 intervention group. After STZ-induced 2 weeks, NRG1 intervention daily for consecutive 7 days. 4 weeks after NRG1 intervention, both the mechanical withdrawal threshold and the morphological changes of the dorsal root ganglion and sural nerve were observed. Meanwhile, the expression of NGF, IL-1, TNF- in spinal cord were determined. Results: Compared with the diabetic group, NRG1 treatment improved the mechanical withdrawal threshold in diabetic rats, pathological changes of dorsal root ganglion and sural nerve were alleviated by NRG1 treatment with electron microscopy imagine. Moreover, compared with the control group, the expression of NGF was significantly decreased and the production of IL-1, TNF- were markedly induced in diabetic group. Furthermore, NRG1 treatment could normalized the above effect as compared to diabetic group. Conclusion: NRG1 exerted positive effects on the behavioral and pathological changes of rats with STZ-induced diabetic neuropathic pain, the underlying mechanism might be related to the promotion of NGF excretion and the inhibition of inflammatory cytokines excretion.(AU)

Phytotherapy in reducing glycemic index and testicular oxidative stress resulting from induced diabetes: a review / Fitoterapia na redução da glicemia e do estresse oxidativo testicular resultantes do diabetes experimental: uma revisão

Oxidative stress plays a main role in the development of diabetes complications. The impairment of gonadal antioxidant potential and endocrine disturbance in diabetic males causes testicular damage and failure in sperm production. Plants have been widely used to control diabetes due their hypoglycemic and antioxidant potential, contributing towards the recovery of testicular function. Current study comprises a review of the literature on the main medicinal plants used in the recovery of testicular oxidative damage in animals with experimental diabetes. Eighteen plant species in the nineteen studies selected from the search strategy were evaluated. Plant extracts were evaluated according to their effects on blood glucose and insulin levels, antioxidant enzymes and oxidant levels, lipid peroxidation, total protein, testosterone levels, gonadosomatic index, diameter of seminiferous tubules, seminiferous epithelium height and integrity, number of germ cells at stage VII and apoptosis in the seminiferous epithelium, sperm production, motility, viability and morphology. After the analysis of the studies, it was observed that plant species, used alone or in combination, may control testicular oxidative damage triggered by diabetes. The antioxidant potential varies among species, with some plants proving to have a better performance in the recovery of reproduction parameters than others.(AU)

O estresse oxidativo desempenha um dos principais papéis no desenvolvimento das complicações do diabetes. Em machos diabéticos, as alterações ao potencial antioxidante gonadal e os distúrbios endócrinos resultam em danos testiculares e falhas na produção de espermatozoides. Plantas têm sido amplamente utilizadas como um método de controle do diabetes devido aos seus potenciais hipoglicemiante e antioxidante, contribuindo para a recuperação da função testicular. Assim, o objetivo deste estudo é fazer uma revisão da literatura sobre as principais plantas medicinais utilizadas na recuperação de danos oxidativos testiculares em animais induzidos ao diabetes experimental. Nos dezenove estudos selecionados a partir da estratégia de busca, dezoito espécies de plantas foram utilizadas. Os extratos das espécies vegetais foram avaliados de acordo com os seus efeitos nas concentrações de glicose e insulina, níveis das enzimas antioxidantes e dos oxidantes, peroxidação lipídica, quantidade de proteínas totais, níveis de testosterona, índice gonadossomático, diâmetro dos túbulos seminíferos, altura e integridade do epitélio seminífero, número de células germinativas no estágio VII, número de células em apoptose no epitélio seminífero, produção, motilidade, viabilidade e morfologia espermática. Depois das análises aos estudos, foi observado que as espécies vegetais, sozinhas ou em combinação, podem ajudar a controlar os danos oxidativos testiculares desencadeados pelo diabetes. Contudo, o potencial antioxidante varia entre as espécies, algumas tenho uma melhor performance na recuperação dos parâmetros reprodutivos do que outras.(AU)

The effects of photobiomodulation therapy on Staphylococcus aureus infected surgical wounds in diabetic rats. A microbiological, histopathological, and biomechanical study

PURPOSE:To evaluate the effects of photobiomodulation therapy (PBMT) at 685 nm on diabetic wound healing in rats suffering from bacterial infection induced by Staphylococcus aureus (S. aureus).METHODS:Thirty streptozotocin-induced diabetic rats were allocated into two groups: control and PBMT. A 4-cm full-thickness linear-incision was made on the dorsal midline and was contaminated with S. aureus. The wounds in the PBMT group were irradiated daily for 5 consecutive days, starting 3 days after the induction and always in the mornings.RESULTS:The result revealed that PBMT resulted in a significant decrease in S. aureus CFU in the PBMT group in comparison to the control group (P<0.05). The length of wounds, in the 2nd and 3rd weeks, in the PBMT group were significantly shorter compared to the control group (P<0.05). PBMT caused a significant increase in the histological parameters in comparison to the control group (P<0.05). Moreover, PBMT significantly increased the breaking strength of the surgical scars produced in the skin of the PBMT group when compared to the control group (P<0.05).CONCLUSION:Photobiomodulation therapy may be useful in the management of wound infection through a significant bacterial growth inhibition and an acceleration of wound healing process.(AU)

Use of insulin-like growth factor in the healing of open wounds in diabetic and non-diabetic rats

To analyze the effects of application of 1% and 3% insulin-like growth factor I (IGF-1) cream on the process of wound healing in induced skin lesions in diabetic and non-diabetic rats and evaluate its effect on expression of myofibroblasts. METHODS: Ninety-six Wistar adult male rats were divided into six groups, with 16 rats in each group, as follows: group 1: non-diabetic, untreated; group 2: non-diabetic, treated with 1% IGF-1 cream; group 3: non-diabetic, treated with 3% IGF-1 cream; group 4: diabetic, untreated; group 5: diabetic, treated with 1% IGF-1 cream; and group 6: diabetic, treated with 3% IGF-1 cream. In groups 4, 5, and 6, diabetes was induced by intravenous injection of alloxan. After diabetes had been induced, animals were mantained for 3 months. The experimental procedure consisted of the creation of a circular incision of 0.9 mm in diameter using a metal punch. Following this, wounds were treated daily according to the assigned treatment regimen. Groups 2 and 5 were treated with 1% IGF-1 cream, groups 3 and 6 with 3% IGF-1 cream, and groups 1 and 4 and the untreated groups with 0.9% saline solution. From each group, samples from 4 rats were taken at three, seven, 14, and 21 days after the injury. Samples were fixed in 10% formalin to prepare slides for histological analysis. Slides stained with hematoxylin-eosin (H&E) and Masson were observed vascular proliferation, mononuclear cells, polymorphonuclear cells, fibroblast proliferation, re-epithelialization, and collagen fibers. This study analyzed the expression of α-smooth muscle actin using specific antibodies to correlate the temporal expression of α-smooth muscle-specific actin (α-SM actin), a molecular marker for myofibroblast transformation. RESULTS: Macroscopic observation of wounds showed a more rapid re-epithelialization of wounds treated with IGF. Regarding acute inflammatory reactions, the results of the analysis of vascular.(AU)

Urethral dysfunction due to alloxan-induced diabetes. Urodynamic evaluation and action of sildenafil citrate

To evaluate the effect of diabetes mellitus and of sildenafil citrate on female urethral function. Twenty nine female rats were divided into four groups: G1 - (n=9), normal rats; G2 - (n=6), normal rats treated with sildenafil citrate; G3 - (n=9) rats with alloxan-induced diabetes; G4 - (n=5) rats with alloxan-induced diabetes treated with sildenafil citrate. Under anesthesia, urodynamic evaluation was performed by cystometry and urethral pressure simultaneously. A significant increase in urethral pressure was observed during micturition. Sildenafil citrate can partially reduced urethral pressure in diabetic female rats.(AU)

Alloxan diabetes alters the tensile strength, morphological and morphometric parameters of abdominal wall healing in rats

To investigate the effects of alloxan diabetes on the abdominal wall healing of rats undergoing laparotomy. METHODS: Ninety-six male Wistar rats weighing between 200 and 300 grams, divided into two groups: non-diabetic group (G1) and another with untreated diabetes (G2). Three months after diabetes induction, the animals underwent a 5cm-long- laparotomy and 5.0 nylon monofilament suture. After the surgery, 12 animals from each group were euthanized on days 4, 14, 21 and 30 corresponding to the moments M1, M2, M3 and M4. In each moment a fragment of the abdominal wall containing the scar was removed for tensile strength measurement, histological and morphometric study. Clinical and biochemical parameters were also analyzed. RESULTS: G2 animals showed parameters compatible with severe diabetes and decreased plasma levels of insulin. The tensile strength in G2 was significantly smaller in M2 and M4, with a tendency to fall in the other two. Through light microscope, diabetic animals showed more difficulty to increase collagen density and contraction. G2 animals showed high cellularity of fibroblasts in later healing moments, with collagen thinning in M2 and M4. CONCLUSION: The abdominal wound healing in untreated diabetic animals was altered and led to a higher incidence of dehiscence and infections.(AU)

Cenostigma macrophyllum Tul. on the healing of skin wounds in rats with Diabetes mellitus

PURPOSE: To investigate the effect of Cenostigma macrophyllum Tul. in the tissue repair process of skin lesions in rats with induced Diabetes mellitus. METHODS: Sixty-three male Wistar rats were distributed into three groups: control (C), diabetic (D), and diabetic treated with an oil-in-water emulsion of the plant (DPL) subdivided according to time of observation (seven, 14, and 28 days). Diabetes was induced by administration of by injection of streptozotocin (50 mg/kg, after a 12-h fast) into the penile vein and confirmed by glucose levels exceeding 240 mg/dL. Held surgical lesion (2.5 cm in diameter) on the back of the animals. The DPL received topical application of group of the oil-in-water emulsion plant (0.5ml). To evaluate the levels of nitric oxide, was collected 5ml of blood from the abdominal aorta, after his euthanasia. The samples of interest were sent for routine histological processing. RESULTS:A reduction in the percentage of inflammatory cells and increased numbers of fibroblasts in the group DPL, seven days, compared to the other groups. At 14 days, the DPL group also showed a higher concentration of nitric oxide (p<0.01) than in groups C and D. CONCLUSION: The oil-in-water emulsion of C. macrophyllum Tul accelerated wound healing in diabetic rats.(AU)

Zinc sulphate administered by transdermal iontophoresis improves breaking strength of surgical wounds in skin of alloxan-induced diabetic rats

PURPOSE:To investigate the effect of zinc sulphate administered by transdermal iontophoresis (TDI) on mechanical resistance of surgical wounds performed in the skin of diabetic rats. METHODS:One hundred and sixty male Wistar rats weighing approximately 250g were submitted to an incision surgery at the anterior region of abdomen and randomly distributed into four experimental groups with 40 non-diabetic control animals (G1) and 40 untreated diabetic animals (G2), both without any treatment of incisions; 40 non-diabetic animals (G3) and 40 untreated diabetic animals (G4), both with incisions treated with zinc sulphate, administered for a period of four consecutive days after surgery, in sessions of ten minutes duration, using a continuous-current electrostimulator (Zn + TDI). Each experimental group was further divided into four subgroups with ten rats each to be evaluated on the 4th, 7th, 14th, and 21st day after surgery. In each period were analyzed clinical and laboratory from the animals, and measured the breaking strength and hydroxyproline content (OH-P) of the skin scars. RESULTS: Breaking strength (BS) was significantly reduced (p<0.05) in skin scars of untreated diabetic rats (G2) on the 7th, 14th, and 21st postoperative days when compared to non-diabetic control rats (G1). In contrast, BS in skin scars of non-diabetic and untreated diabetic rats (G3, G4) treated with Zn + TDI showed significant increase (p<0.05) in those periods when compared with their respective controls with untreated incisions. The OH-P content of the scars did not show statistically significant variation in all studied groups at four different times evaluated after surgery. CONCLUSIONS: Zinc sulphate administered by transdermal iontophoresis had beneficial effect on the mechanical resistance of scars produced in the skin of diabetic rats.(AU)

Evaluation of nerve regeneration in diabetic rats

PURPOSE: To compare sciatic nerve regeneration between non-diabetic (control) and streptozotocin-induced diabetic Wistar rats. METHODS:Four subgroups were evaluated. CN: Non-diabetic rats submitted to neurorrhaphy (n=9); DN: Diabetic rats submitted to neurorrhaphy (n=9); CG: Non-diabetic rats submitted to nerve grafting (n=10); DG: Diabetic rats submitted to nerve grafting (n=9). The nerve regeneration was evaluated by walking track analysis (sciatic functional index), electrophysiological test, histomorphometric analysis and triceps surae muscle weight. RESULTS:At 60 days post-surgery, functional recovery of DN was similar to that of the non-diabetic rats (CN, CG), but DG didn't achieve the same. Evoked potential amplitudes showed no statistically significant differences among subgroups. Triceps surae muscle was heavier in CN. No statistically significant differences were observed between the control and diabetes subgroups with respect to histomorphometric analysis. CONCLUSION: After 60 days, DN had a functionally similar recovery to that of the control animals, whereas nerve grafting in diabetic rats didn't allow the same. The muscle atrophy was lower in CN. In the rest of evaluations, as electrophysiological and histomorphometric, diabetic rats were not different from control ones.(AU)

Diabetes mellitus triggers oxidative stress in the liver of alloxan-treated rats: a mechanism for diabetic chronic liver disease

PURPOSE: To investigate whether Diabetes mellitus chemically induced by alloxan is capable of changing, in the long term, the oxidative balance in the liver tissue of rats. METHODS: Sixty male Wistar rats, weighing 250-280g, were randomly distributed into two experimental groups: NG - 30 non-diabetic control rats; DG - 30 alloxan- induced diabetic rats without any treatment for the disease. Each group was further divided into three subgroups containing ten rats each, which were sacrificed after one, three and six months of follow-up, respectively. Blood glucose, urinary glucose, glycosylated hemoglobin and insulin were determined in the plasma of all animals at the beginning of the experiment and prior to all sacrifice periods. The concentrations of lipid hydroperoxides (HP) and the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were also measured in the liver tissue of all animals. RESULTS: Rats from the DG group showed high levels of blood glucose, urinary glucose, and glycosylated hemoglobin, with significantly lower plasma insulin levels than those observed in NG rats (p<0.001). Diabetic animals also showed increased concentration of HP free radicals in the liver tissue as compared to those shown by NG animals after one, three and six months of follow-up. In contrast, the antioxidant activity of the enzymes SOD, CAT and GSH-Px was significantly reduced in all follow-up periods (p<0.01). CONCLUSIONS: Diabetes determines oxidative stress in the liver, which is characterized by increased concentration of reactive oxygen species (ROS) in tissue and significant reduction in their antioxidant defenses. Such oxidative unbalance in the liver cells may play a relevant role in the genesis of the diabetic chronic liver disease, including the non-alcoholic fatty liver disease and its occasional progression to steatohepatitis and cirrhosis.(AU)

Experimental diabetes exacerbates skin transplant rejection in rats

PURPOSE: To investigate the effect of chronic experimental diabetes on skin allografts in rats as a simple model that could clarify some basic aspects and mechanisms involved in transplant rejection in diabetes compared to normal animals. METHODS: Skin grafting was performed with fragments of tail skin from sex matched non diabetic Wistar rats engrafted onto the thoracic area of diabetic and non diabetic recipients. Grafts were scored for rejection every other day and were removed on day 14. Skin grafts were graded according to the following itens: no rejection; or rejection including: acute, chronic and humoral and/or cellular rejection. Statistical analysis was performed using JMP 5.1 software with ANOVA test. Diabetes was induced with IV injection of alloxan 40 mg/kg. RESULTS: Inflammatory vascular infiltrate compromising the endothelium with areas of fibrinoid necrosis and thrombosis characteristics of acute humoral rejection and subendothelial lymphocyte infiltrate typical of acute cellular rejection were significantly (p<0.003) higher in diabetic than in non diabetic recipients as the inflammatory infiltrate in the epidermis (p<0.002). CONCLUSION: Skin transplant acute rejection from chronic alloxan diabetic rats to normal tissue was significantly more intense than the acute rejection between normal rats.(AU)

Simvastatin attenuates neutrophil recruitment in one-lung ventilation model in rats

PURPOSE: To investigate the anti-inflammatory effects of simvastatin in rats undergoing one-lung ventilation (OLV) followed by lung re-expansion. METHODS: Male Wistar rats (n=30) were submitted to 1-h OLV followed by 1-h lung re-expansion. Treated group received simvastatin (40 mg/kg for 21 days) previous to OLV protocol. Control group received no treatment or surgical/ventilation interventions. Measurements of pulmonary myeloperoxidase (MPO) activity, pulmonary protein extravasation, and serum levels of cytokines and C-reactive protein (CRP) were performed. RESULTS: OLV significantly increased the MPO activity in the collapsed and continuously ventilated lungs (31% and 52% increase, respectively) compared with control (p<0.05). Treatment with simvastatin significantly reduced the MPO activity in the continuously ventilated lung but had no effect on lung edema after OLV. The serum IL-6 and CRP levels were markedly higher in OLV group, but simvastatin treatment failed to affect the production of these inflammatory markers. Serum levels of IL-1β, TNF-α and IL-10 remained below the detection limit in all groups. CONCLUSIONS: In an experimental one-lung ventilation model pre-operative treatment with simvastatin reduces remote neutrophil infiltration in the continuously ventilated lung. Our findings suggest that simvastatin may be of therapeutic value in OLV-induced pulmonary inflammation deserving clinical investigations.(AU)