Benefits of pentoxifylline for skin flap tissue repair in rats

Purpose To assess the action of pentoxifylline, administered by subcutaneous route, on skin flap tissue repair in rats, and to verify the histological aspects and biomarkers. Methods Thirty-two male Wistar rats were divided into four groups: control (CT) and treated with pentoxifylline (P1, P3 and P5). Modified McFarlane technique flap was used. Ten days later, the animals were euthanized and the areas of viable and necrotic tissue were evaluated. Hematoxylin/eosin staining was used to assess the morphometric characteristics of the number of vessels and epithelial thickness. Picrosirius red was used to assess collagen density. VEGF and TGF-beta1 levels on the skin flap and serum of the animals were measured by the ELISA method. Results The macroscopic evaluation of the skin flap dimensions showed reduced necrotic tissue in the pentoxifylline (p < 0.05) treated groups. There was an increase in angiogenesis and reepithelization, demonstrated by analyses with an increased number of vessels (p 0.05), VEGF and epithelial thickness. Fibrogenic effect showed decreased collagen density and TGF-1 in the skin flap and serum. Conclusion The benefits of pentoxifylline administered by subcutaneous route, at dose 100 mg/kg, which was effective to improve the survival of skin flap by acting on tissue repair components, stimulating angiogenesis and reepithelization, in addition to reducing fibrogenesis.(AU)

Pentoxifylline may restore kanamycin-induced renal damage in rats

Background: Kidney damage can be caused by many factors, such as using certain drugs in high doses or over the long term. The use of one such group of drugs, aminoglycosides, which act as Gram-negative antibacterial therapeutic agents, can lead to nephrotoxicity. It has been hypothesized that aminoglycoside-induced nephrotoxicity might be prevented by using pentoxifylline, which has antioxidant and anti-inflammatory effects and improves microcirculation. The objective of this present research was to determine the protective effects of pentoxifylline on kanamycin-induced kidney damage.Materials, Methods & Results: Thirty-two male Wistar rats were divided into four groups as follows: control, pentoxifylline, kanamycin, and kanamycin + pentoxifylline. The control group received intraperitoneal (IP) injections of 0.5 mL normal saline solution once a day (d) (SID) for 20 d; the pentoxifylline group received IP injections of 50 mg/kg pentoxifylline twice a day (BID) for 20 d, the kanamycin group received subcutaneous (SC) injections of 500 mg/kg kanamycin SID for 20 d, and the kanamycin + pentoxifylline group received both SC injections of 500 mg/kg kanamycin SID and IP injections of 50 mg/kg pentoxifylline BID for 20 d. At the end of 20 d, blood samples were taken from the heart by cardiac puncture under general anesthesia. After euthanizing the rats by cervical dislocation under anesthesia, the kidneys were immediately removed, relative kidney weights were calculated, and routine pathologic evaluations were conducted. Hemogram parameters were measured using a blood cell count apparatus and serum biochemical parameters were measured using an autoanalyzer. Kanamycin also caused (P < 0.05) tubular degeneration and tubular dilatation. Although pentoxifylline significantly reduced the level of kanamycin-induced tubular degeneration (P < 0.05), it did not significantly reduce tubular dilatation.[...]

Pentoxifylline may restore kanamycin-induced renal damage in rats

Background: Kidney damage can be caused by many factors, such as using certain drugs in high doses or over the long term. The use of one such group of drugs, aminoglycosides, which act as Gram-negative antibacterial therapeutic agents, can lead to nephrotoxicity. It has been hypothesized that aminoglycoside-induced nephrotoxicity might be prevented by using pentoxifylline, which has antioxidant and anti-inflammatory effects and improves microcirculation. The objective of this present research was to determine the protective effects of pentoxifylline on kanamycin-induced kidney damage.Materials, Methods & Results: Thirty-two male Wistar rats were divided into four groups as follows: control, pentoxifylline, kanamycin, and kanamycin + pentoxifylline. The control group received intraperitoneal (IP) injections of 0.5 mL normal saline solution once a day (d) (SID) for 20 d; the pentoxifylline group received IP injections of 50 mg/kg pentoxifylline twice a day (BID) for 20 d, the kanamycin group received subcutaneous (SC) injections of 500 mg/kg kanamycin SID for 20 d, and the kanamycin + pentoxifylline group received both SC injections of 500 mg/kg kanamycin SID and IP injections of 50 mg/kg pentoxifylline BID for 20 d. At the end of 20 d, blood samples were taken from the heart by cardiac puncture under general anesthesia. After euthanizing the rats by cervical dislocation under anesthesia, the kidneys were immediately removed, relative kidney weights were calculated, and routine pathologic evaluations were conducted. Hemogram parameters were measured using a blood cell count apparatus and serum biochemical parameters were measured using an autoanalyzer. Kanamycin also caused (P < 0.05) tubular degeneration and tubular dilatation. Although pentoxifylline significantly reduced the level of kanamycin-induced tubular degeneration (P < 0.05), it did not significantly reduce tubular dilatation.[...](AU)

Surgery-induced changes in erythrocyte and plasma lipid peroxidation, enzymatic and non-enzymatic antioxidants of female rats: protective role of heparin and pentoxifylline

Background: Intra abdominal adhesions are a complication that occurs after many abdominal surgical procedures, especially gynecological operations. These complications occur by irritating the peritoneum due to such circumstances as infection or surgical trauma, and are considered a pathological part of the healing process of peritoneal injury. It manifests itself with symptoms such as pain, intestinal or urethral obstruction and abdominal abscesses. Oxidative stress due to adhesions plays an important role on adhesion formation. In addition to many researches done at the point of prevention of adhesion and decreasing stress parameters, in this study, it was planned to determine the effect of Heparin (H) and Pentoxifylline (PTX) on malondialdehyde (MDA) and some antioxidant values.Materials, Methods & Results: This study was performed on rats and thirty-seven female Sprague-Dawley rats were randomized into four groups. The first group was sham (Sh) group (n = 7) and laparotomy was performed and 2 mL of 0.9 % NaCl was applied. For all other rats (n = 30) the small intestine was withdrawn and the uterus was uncovered and the anti mesenteric surfaces of the left uterine horn and left abdominal wall were superficially tilted until slight bleeding was seen. Lesion areas have been covered. Two mL 0.9 % NaCl to control (C) group (n = 10), 500 IU heparin to group H, and 25 mg / kg Pentoxifylline to group PTX (n = 10) have been given and then the abdominal incision was closed. The adhesion score of group Sh was found to be more important than C and PTX groups (P < 0.05). The adhesion score of group C was determined to be more significant than group H (P < 0.05). In group Sh, erythrocyte reduced glutathione (GSH) levels were found to be more significant (P < 0.01) than C, H and PTX groups whereas it was found that group C was more significant than group H (P < 0.01).[...]

Surgery-induced changes in erythrocyte and plasma lipid peroxidation, enzymatic and non-enzymatic antioxidants of female rats: protective role of heparin and pentoxifylline

Background: Intra abdominal adhesions are a complication that occurs after many abdominal surgical procedures, especially gynecological operations. These complications occur by irritating the peritoneum due to such circumstances as infection or surgical trauma, and are considered a pathological part of the healing process of peritoneal injury. It manifests itself with symptoms such as pain, intestinal or urethral obstruction and abdominal abscesses. Oxidative stress due to adhesions plays an important role on adhesion formation. In addition to many researches done at the point of prevention of adhesion and decreasing stress parameters, in this study, it was planned to determine the effect of Heparin (H) and Pentoxifylline (PTX) on malondialdehyde (MDA) and some antioxidant values.Materials, Methods & Results: This study was performed on rats and thirty-seven female Sprague-Dawley rats were randomized into four groups. The first group was sham (Sh) group (n = 7) and laparotomy was performed and 2 mL of 0.9 % NaCl was applied. For all other rats (n = 30) the small intestine was withdrawn and the uterus was uncovered and the anti mesenteric surfaces of the left uterine horn and left abdominal wall were superficially tilted until slight bleeding was seen. Lesion areas have been covered. Two mL 0.9 % NaCl to control (C) group (n = 10), 500 IU heparin to group H, and 25 mg / kg Pentoxifylline to group PTX (n = 10) have been given and then the abdominal incision was closed. The adhesion score of group Sh was found to be more important than C and PTX groups (P < 0.05). The adhesion score of group C was determined to be more significant than group H (P < 0.05). In group Sh, erythrocyte reduced glutathione (GSH) levels were found to be more significant (P < 0.01) than C, H and PTX groups whereas it was found that group C was more significant than group H (P < 0.01).[...](AU)

Three cases of canine dermatomyositis-like disease

Background: Dermatomyositis is an idiopathic, inflammatory/immunemediated disease of the skin, muscles and blood vessels of hereditary nature and unclear pathogenesis. This familial disease has been described in certain breeds, especially collies and Shetland sheep dogs and is of rare occurrence in mongrel dogs. To describe and discuss three clinical cases of dermatomyositis-like disease and provide a brief review of the literature.Cases: Three young mongrel dogs are included in this report. Case 1: Mandarino, a 4-year-old mongrel dog, having a history of skin lesions for at least a year. Showed an underweight patient, skin ulcers, crusts, alopecia, peri-ocular scarring causing severe lagophthalmia and a corneal ulcer. Muscle atrophy was most notable in the head and legs; the dog had difficulty and pain walking. Treatment was initialised with cephalexin 30 mg/kg BID, pentoxifylline 25 mg/kg BID, and prednisone 2.2 mg/kg SID. The patient was presented after two weeks for follow up; the anaemia and skin condition had improved, the weight had increased by 2 kg, dysphagia and locomotor abnormalities were not present. Case 2: Milagros, a mongrel female dog approximately two years of age, rescued from a shelter. Physical examination showed facial alopecia, erythema and scarring of the periocular skin, crusting and scaling in alopecic areas, pinnae tip necrosis and crusting, ear alopecia, tail tip necrosis and crusting. Also present were distal limb alopecia, crusting and ulcers in areas of trauma in the hock and carpal surfaces; some nails presented onychorhexis and onychoschizia. The patient has been treated for 12 months with a good clinical outcome, with pentoxifylline, azathioprine 2.2 mg/kg EOD alternating with prednisone 1 mg/kg EOD. Case 3: Chuchito, an 11-month-old male mongrel rescued dog had been previously hospitalised due to his skin condition.[...]

Three cases of canine dermatomyositis-like disease

Background: Dermatomyositis is an idiopathic, inflammatory/immunemediated disease of the skin, muscles and blood vessels of hereditary nature and unclear pathogenesis. This familial disease has been described in certain breeds, especially collies and Shetland sheep dogs and is of rare occurrence in mongrel dogs. To describe and discuss three clinical cases of dermatomyositis-like disease and provide a brief review of the literature.Cases: Three young mongrel dogs are included in this report. Case 1: Mandarino, a 4-year-old mongrel dog, having a history of skin lesions for at least a year. Showed an underweight patient, skin ulcers, crusts, alopecia, peri-ocular scarring causing severe lagophthalmia and a corneal ulcer. Muscle atrophy was most notable in the head and legs; the dog had difficulty and pain walking. Treatment was initialised with cephalexin 30 mg/kg BID, pentoxifylline 25 mg/kg BID, and prednisone 2.2 mg/kg SID. The patient was presented after two weeks for follow up; the anaemia and skin condition had improved, the weight had increased by 2 kg, dysphagia and locomotor abnormalities were not present. Case 2: Milagros, a mongrel female dog approximately two years of age, rescued from a shelter. Physical examination showed facial alopecia, erythema and scarring of the periocular skin, crusting and scaling in alopecic areas, pinnae tip necrosis and crusting, ear alopecia, tail tip necrosis and crusting. Also present were distal limb alopecia, crusting and ulcers in areas of trauma in the hock and carpal surfaces; some nails presented onychorhexis and onychoschizia. The patient has been treated for 12 months with a good clinical outcome, with pentoxifylline, azathioprine 2.2 mg/kg EOD alternating with prednisone 1 mg/kg EOD. Case 3: Chuchito, an 11-month-old male mongrel rescued dog had been previously hospitalised due to his skin condition.[...](AU)

The role of ischemic preconditioning and pentoxifylline in intestinal ischemia/reperfusion injury of rats

Purpose: To investigate the role of ischemic preconditioning (IPC) and pentoxifylline (PTX) in intestinal mucosa ischemia/reperfusion injury (IR). Methods: Thirty rats were assigned to 5 groups (N=6): (CG): no clamping of the superior mesenteric artery (90 min.); (IR-SS): saline + ischemia (30 min.) + reperfusion (60 min.); (IR-PTX): PTX + ischemia (30min.) + reperfusion (60 min.); (IPC-IR-SS): 5 min. of ischemia + 5 minutes of reperfusion (IPC) + saline + ischemia (30 min.) + reperfusion (60 min.); (IPC-IR-PTX ): 5 min. of ischemia + 5 min. of reperfusion (IPC) + PTX + 30 min. of I + 60 minutes of R. Results: The IR-PTX, IPC-IR-SS and IPC-IR-PTX groups had significantly lower scores of mucosa damage than the IR-SS group. IR-PTX group showed higher scores than the IPC-IR-PTX group, in accordance with the hypothesis of a favorable effect of IPC alone or in association with PTX. Additionally, IPC-IR-SS had a higher damage score than the IPC-IR-PTX. The villi height and crypt depth were similar in all groups. The villi height in the IR-SS was significantly lower. Conclusion: Ischemic preconditioning or pentoxifylline alone protect the intestinal mucosa from ischemia/reperfusion injury. However, they do not have a synergistic effect when applied together.(AU)

The expression of endothelial and inducible nitric oxide synthase and apoptosis in intestinal ischemia and reperfusion injury under the action of ischemic preconditioning and pentoxifylline

Purpose:To investigate the expression of nitric oxide synthase (NOS) and apoptosis associated with ischemic preconditioning (IPC) and pentoxifylline (PTX) in intestinal ischemia (I) and reperfusion (R) injury.Methods:Thirty male rats were assigned to 5 groups: (CG), no clamping of the superior mesenteric artery (90 minutes); (IR-SS) saline + ischemia (30 minutes) + reperfusion (60 minutes); (IR-PTX) PTX + ischemia (30 minutes) + reperfusion (60 minutes); (IPC-IR-SS) 5 minutes of ischemia + 5 minutes of reperfusion (IPC) + saline + I(30 minutes)+R(60 minutes); and (IPC-IR-PTX) IPC + PTX + I(30 minutes)+ R(60 minutes).Results:The application of IPC and PTX showed a significantly lower immunohistochemistry reaction for active caspase-3 (P<0.05) compared to IR+SS. The number of cells immunoreactive to BCL-2 was higher in the IR-PTX group (P>0.05). The NOS-2 expression (qRTPCR) in the IR-PTX group (P<0.05) was higher than the values for the IPC+IR-SS and IPC-IR-PTX groups. The NOS-3 expression was significantly upper in the IPC-IR-PTX group than in the CG (P<0.05), the IR-SS (P<0.05) and the IR-PTX (P<0.05) groups.Conclusions:The BCL-2 and active caspase-3 showed beneficial effects on PTX and IPC. The expression of NOS-2 and NOS-3 in the IPC and IPC-PTX groups showed no synergistic effect.(AU)

Utilização de pentoxifilina e antioxidantes na criopreservação do sêmen bovino: qualidade seminal e estresse oxidativo / Utilization of pentoxifylline and antioxidants in cryopreservation of bovine semen: semen quality and oxidative stress

O presente estudo avaliou a adição da pentoxifilina, tocoferol, ascorbato e suas combinações sobre a proteção da célula espermática bovina contra os efeitos deletérios da criopreservação. Foram utilizados 24 touros Nelores (Bos taurus indicus), criados em sistema semi-intensivo. Foi coletado um ejaculado de cada reprodutor, diluídos em TRIS-citratogema-glicerol e divididos em seis partes. Cada parte foi suplementada da seguinte maneira: sem aditivos (controle), tocoferol (10 mmol/mL), tocoferol (10 mmol/mL) + pentoxifilina (1mg/mL), ascorbato (0,45mg/mL), ascorbato (0,45mg/mL) + pentoxifilina (1mg/mL) ou pentoxifilina (1mg/mL). Após o descongelamento, as amostras foram avaliadas quanto à motilidade e características do movimento, integridade da membrana plasmática e de acrossomo e atividade mitocondrial. Os níveis de peroxidação lipídica espontânea e induzida foram avaliados pela produção de substâncias reativas ao ácido tiobarbitúrico (TBARS). A suplementação com pentoxifilina, tocoferol, ascorbato e suas combinações, não alterou (P>0,05) a atividade mitocondrial, integridade acrossomal, e a concentração de TBARS espontâneo e induzido. A adição de tocoferol + pentoxifilina reduziu a motilidade progressiva quando comparado ao ascorbato e também a integridade da membrana espermática quando comparado ao controle e ao ascorbato (P˂0,05). Já a adição de ascorbato + pentoxifilina foi deletéria sobre linearidade em comparação ao tratamento ascorbato (P˂0,05). A adição de ascorbato, tocoferol e pentoxifilina individualmente ou em combinação, não foi eficiente em diminuir os danos causados pela criopreservação e estresse oxidativo em amostras pós descongelamento de sêmen bovino.

The present study evaluated the addition of pentoxifylline, tocopherol and ascorbate and their combinations on the protection of bovine spermatic cells against the deleterious effects of cryopreservation. A total of 24 Nelore bulls (Bos Taurus indicus) were included in this study, raised in a semi-intensive system. One ejaculation was collected from each bull and diluted in tris-citrate-yolk-glycerol, divided into six portions, and then supplemented with: no additives (control); tocopherol (10 mmol/ml), tocopherol (10 mmol/ml) + pentxoifylline (1 mg/ml), ascorbate (0.45 mg/ml), ascorbate (0.45 mg/ml) + pentoxifylline (1 mg/ml) and pentxoifylline (1 mg/ml). After thawing, the samples were evaluated for motility and characteristics of movement, acrosomal and plasma membrane integrity, and mitochondrial activity. Spontaneous and induced lipid peroxidation levels were evaluated by the production of thiobarbituric acid reactive substances (TBARS). Supplementation with pentoxifylline, tocopherol and ascorbate and their combinations, did not alter mitochondrial activity, acrosomal integrity, or the spontaneous and induced TBARS concentration (P>0.05). The ascorbate, tocopherol and pentoxifylline additions, both individually and in combinations, were inefficient in decreasing the damage caused by cryopreservation and oxidative stress in post-thawed bovine semen samples.

Utilização de pentoxifilina e antioxidantes na criopreservação do sêmen bovino: qualidade seminal e estresse oxidativo / Utilization of pentoxifylline and antioxidants in cryopreservation of bovine semen: semen quality and oxidative stress

O presente estudo avaliou a adição da pentoxifilina, tocoferol, ascorbato e suas combinações sobre a proteção da célula espermática bovina contra os efeitos deletérios da criopreservação. Foram utilizados 24 touros Nelores (Bos taurus indicus), criados em sistema semi-intensivo. Foi coletado um ejaculado de cada reprodutor, diluídos em TRIS-citratogema-glicerol e divididos em seis partes. Cada parte foi suplementada da seguinte maneira: sem aditivos (controle), tocoferol (10 mmol/mL), tocoferol (10 mmol/mL) + pentoxifilina (1mg/mL), ascorbato (0,45mg/mL), ascorbato (0,45mg/mL) + pentoxifilina (1mg/mL) ou pentoxifilina (1mg/mL). Após o descongelamento, as amostras foram avaliadas quanto à motilidade e características do movimento, integridade da membrana plasmática e de acrossomo e atividade mitocondrial. Os níveis de peroxidação lipídica espontânea e induzida foram avaliados pela produção de substâncias reativas ao ácido tiobarbitúrico (TBARS). A suplementação com pentoxifilina, tocoferol, ascorbato e suas combinações, não alterou (P>0,05) a atividade mitocondrial, integridade acrossomal, e a concentração de TBARS espontâneo e induzido. A adição de tocoferol + pentoxifilina reduziu a motilidade progressiva quando comparado ao ascorbato e também a integridade da membrana espermática quando comparado ao controle e ao ascorbato (P˂0,05). Já a adição de ascorbato + pentoxifilina foi deletéria sobre linearidade em comparação ao tratamento ascorbato (P˂0,05). A adição de ascorbato, tocoferol e pentoxifilina individualmente ou em combinação, não foi eficiente em diminuir os danos causados pela criopreservação e estresse oxidativo em amostras pós descongelamento de sêmen bovino.(AU)

The present study evaluated the addition of pentoxifylline, tocopherol and ascorbate and their combinations on the protection of bovine spermatic cells against the deleterious effects of cryopreservation. A total of 24 Nelore bulls (Bos Taurus indicus) were included in this study, raised in a semi-intensive system. One ejaculation was collected from each bull and diluted in tris-citrate-yolk-glycerol, divided into six portions, and then supplemented with: no additives (control); tocopherol (10 mmol/ml), tocopherol (10 mmol/ml) + pentxoifylline (1 mg/ml), ascorbate (0.45 mg/ml), ascorbate (0.45 mg/ml) + pentoxifylline (1 mg/ml) and pentxoifylline (1 mg/ml). After thawing, the samples were evaluated for motility and characteristics of movement, acrosomal and plasma membrane integrity, and mitochondrial activity. Spontaneous and induced lipid peroxidation levels were evaluated by the production of thiobarbituric acid reactive substances (TBARS). Supplementation with pentoxifylline, tocopherol and ascorbate and their combinations, did not alter mitochondrial activity, acrosomal integrity, or the spontaneous and induced TBARS concentration (P>0.05). The ascorbate, tocopherol and pentoxifylline additions, both individually and in combinations, were inefficient in decreasing the damage caused by cryopreservation and oxidative stress in post-thawed bovine semen samples.(AU)

Direct intraperitoneal resuscitation with lidocaine, methylene blue and pentoxiphylline combination does not decreases inflammation after intestinal ischemia-reperfusion injury in rats

PURPOSE:To evaluate the effects of an intraperitoneal solution of methylene blue (MB), lidocaine and pentoxyphylline (PTX) on intestinal ischemic and reperfusion injuryMETHODS:Superior mesenteric artery was isolated and clamped in 36 adult male Sprague Dawley rats. After 60 minutes, clamp was removed and a group received intraperitoneally UNITO solution (PTX 25mg/kg + lidocaine 5mg/kg + MB 2mg/kg), while the other group was treated with warm 0.9% NaCl solution. Rats were euthanized 45 min after drug administration. Lung and bowel were collected for histological evaluation (using Park's score) and determination of myeloperoxidase (MPO) and malondialdehyde (MDA) levels.RESULTS:Control samples showed lymphoplasmocytic infiltrate and crypt necrosis of villi. MPO and MDA measurements shown no differences between treated and control groups.CONCLUSION:The combination of lidocaine, methylene blue and pentoxyphylline administered intraperitoneally at the studied dose, did not decreased histological lesion scores and biochemical markers levels in intestinal ischemia/reperfusion injury.(AU)

Pentoxifylline and prostaglandin E1 action on ischemia and reperfusion of small intestine tissue in rats. An immunohistochemical study1

PURPOSE: To investigate the action of pentoxifylline (PTX) and prostaglandin E1 (PGE1) on ischemia and reperfusion of small intestine tissue in rats, using immunohistochemical analysis. METHODS: Thirty-five Wistar rats were distributed as follows: group A (n=10): subjected to intestinal ischemia and reperfusion for 60 min, with no drugs; group B (n=10): PTX given during tissue ischemia and reperfusion; group C (n=10): PGE1 given during tissue ischemia and reperfusion; group D (n=5): sham. A segment of the small intestine was excised from each euthanized animal and subjected to immunohistochemical examination. RESULTS: Mean number of cells expressing anti-FAS ligand in the crypts was highest in Group A (78.9 ± 17.3), followed by groups B (16.7 ± 2.8), C (11.3 ± 1.8), and D (2.5 ± 0.9), with very significant differences between groups (p<0.0001). CONCLUSIONS: The use of pentoxifylline or prostaglandin E1 proved beneficial during tissue reperfusion. The immunohistochemical results demonstrated a decrease in apoptotic cells, while protecting other intestinal epithelium cells against death after reperfusion, allowing these cells to renew the epithelial tissue.(AU)

Histological modification in TRAM flap in rats treated with pentoxifylline

To investigate the blood vessels' concentration in TRAM flap's rat model, in the presence of pentoxifylline. 32 male, Wistar-EPM rats were divided into two groups. Control group (C): 0.5 ml of saline, intraperitoneally, once a day, for seven days before flap elevation; PTX group (P): pentoxifylline (20mg/kg/day), intraperitoneally, for seven days before flap elevation. After that, they were submitted to a caudal unipedicle TRAM flap. On the fifth postoperative day, percentages of flap necrosis were determined via the "paper template" method and Tram flap's zone IV skin biopsies were taken for histological analysis. The mean percentage of flap necrosis in group C was 58.7 % and in group P, 31.1 (Wilcoxon test; p = 0.003). Mean capillary vessels number in zone IV's skin in C group was 33.4 and in P group was 71.9 (p=0.008). Pentoxifylline was effective reducing the necrosis in the caudal unipedicle TRAM flap in the rat as well as increasing the number of capillaries in an ischemic zone (zone IV).(AU)

Pentoxifylline associated to hypertonic saline solution attenuates inflammatory process and apoptosis after intestinal ischemia/reperfusion in rats

PURPOSE:To evaluate intestinal inflammatory and apoptotic processes after intestinal ischemia/reperfusion injury, modulated by pentoxifylline and hypertonic saline.METHODS:It was allocated into four groups (n=6), 24 male Wistar rats (200 to 250g) and submitted to intestinal ischemia for 40 min and reperfusion for 80 min: IR (did not receive any treatment); HS group (Hypertonic Saline, 4ml/kg-IV); PTX group (Pentoxifylline, 30mg/kg-IV); HS+PTX group (Hypertonic Saline and Pentoxifylline). All animals were heparinized (100U/kg). At the end of reperfusion, ileal fragments were removed and stained on hematoxylin-eosin and histochemical studies for COX-2, Bcl-2 and cleaved caspase-3.RESULTS:The values of sO2 were higher on treated groups at 40 minutes of reperfusion (p=0.0081) and 80 minutes of reperfusion (p=0.0072). Serum lactate values were lower on treated groups after 40 minutes of reperfusion (p=0.0003) and 80 minutes of reperfusion (p=0.0098). Morphologic tissue injuries showed higher grades on IR group versus other groups: HS (p=0.0006), PTX (p=0.0433) and HS+PTX (p=0.0040). The histochemical study showed lesser expression of COX-2 (p=0.0015) and Bcl-2 (p=0.0012) on HS+PTX group. A lower expression of cleaved caspase-3 was demonstrated in PTX (p=0.0090; PTXvsIR).CONCLUSION:The combined use of pentoxifylline and hypertonic saline offers best results on inflammatory and apoptotic inhibitory aspects after intestinal ischemia/reperfusion.(AU)

A comparative study of pentoxifylline effects in adult and aged rats submitted to lung dysfunction by thermal injury

PURPOSE: To investigate the protective effects of pentoxifylline against lung injury observed after dorsal scald in aged animals. METHODS: Adult (eight months old) and aged (20 months old) rats were subjected to thermal injury or sham procedure. The six hours post-trauma animals received pentoxifylline and after 24 hours were euthanatized and lung tissue samples collectedted. The bronchoalveolar lavage fluid was evaluated for total protein content and tumor necrosis factor-alpha cytokine. Malondialdehyde and myeloperoxidase activety in the lung homogenate were measured and a histological lung examination was undertaken. RESULTS: Burn injury induced oxidative stress in lung homogenate was higher in elderly-burned rats compared to adult-burned rats (p<0.001). Total protein and cytokine in bronchoalveolar lavage increased in the elderly-burned group when compared to the adult-burned group (p<0.001). All parameters decreased in bolth groups treated with pentoxifylline (p<0.05). CONCLUSIONS: The injury was augmented in elderly rats when compared to adult rats. Damage was reduced with the use of pentoxifylline, however further studies are needed to evaluate the dose-response of the drug.(AU)

Effect of pentoxifylline on the regeneration of rat testicular germ cells after heat shock

High temperature is an important factor for reproduction and can induce testicular degeneration. Pentoxifylline is a methylxanthine phosphodiesterase inhibitor with anti - inflammatory and anti - apoptotic properties. Considering the protective propert ies of pentoxifylline and the harmful effects of heat, the present study aimed to use pentoxifylline to reduce the damage induced by heat to the testis. Adult mal e Wistar rats were exposed to testicular heat shock (43ºC for 15 min) , treated with 50 or 100 mg/ k g of pentoxifylline and evaluated at 3, 7, 15, 30 and 60 days after heat shock. Pentoxifylline treatment did not change testicular weight, histomorphometrical parameters or plasma testosterone concentration. However, pentoxifylline inhibited germ cell apoptosis and reduced the severity of pathological lesions at 30 and 60 days after testicular heat shock. In conclusion, pentoxifylline treatment seem ed to inhibit pro - inflammatory and apoptotic mechanisms triggered by testicular heat shock, improving sper matogenesis regeneration.

Effect of pentoxifylline on the regeneration of rat testicular germ cells after heat shock

High temperature is an important factor for reproduction and can induce testicular degeneration. Pentoxifylline is a methylxanthine phosphodiesterase inhibitor with anti - inflammatory and anti - apoptotic properties. Considering the protective propert ies of pentoxifylline and the harmful effects of heat, the present study aimed to use pentoxifylline to reduce the damage induced by heat to the testis. Adult mal e Wistar rats were exposed to testicular heat shock (43ºC for 15 min) , treated with 50 or 100 mg/ k g of pentoxifylline and evaluated at 3, 7, 15, 30 and 60 days after heat shock. Pentoxifylline treatment did not change testicular weight, histomorphometrical parameters or plasma testosterone concentration. However, pentoxifylline inhibited germ cell apoptosis and reduced the severity of pathological lesions at 30 and 60 days after testicular heat shock. In conclusion, pentoxifylline treatment seem ed to inhibit pro - inflammatory and apoptotic mechanisms triggered by testicular heat shock, improving sper matogenesis regeneration.(AU)

Is there a therapeutic window for pentoxifylline after the onset of acute pancreatitis / Existe uma janela terapêutica para a pentoxifilina após o início da pancreatite aguda?

PURPOSE: To investigate the effects of pentoxifylline (PTX) in experimental acute pancreatitis (AP) starting drug administration after the induction of the disease. METHODS: One hundred male Wistar rats were submitted to taurocholate-induced AP and divided into three groups: Group Sham: sham-operated rats, Group Saline: AP plus saline solution, and Group PTX: AP plus PTX. Saline solution and PTX were administered 1 hour after induction of AP. At 3 hours after AP induction, peritoneal levels of tumor necrosis factor (TNF)-α, and serum levels of interleukin (IL)-6 and IL-10 levels were assayed by Enzyme-Linked Immunosorbent Assay (ELISA). Determinations of lung myeloperoxidase activity (MPO), histological analysis of lung and pancreas, and mortality study were performed. RESULTS: PTX administration 1 hour after induction of AP caused a significant decrease in peritoneal levels of TNF-α and in serum levels of IL-6 and IL-10 when compared to the saline group. There were no differences in lung MPO activity between the two groups with AP. A decrease in mortality was observed in the PTX treatment compared to the saline group. CONCLUSIONS: Administration of PTX after the onset of AP decreased the systemic levels of proinflammatory cytokines, raising the possibility that there is an early therapeutic window for PTX after the initiation of AP.(AU)

OBJETIVO: Investigar os efeitos da pentoxifilina (PTX) na pancreatite aguda (PA) experimental administrando a droga após a indução da doença. MÉTODOS: Cem ratos machos Wistar foram submetidos à indução da PA através da infusão de taurocolato de sódio e divididos em três grupos: Grupo Sham: sham-operated ratos, Grupo Salina: AP e solução salina, e Grupo PTX: AP e PTX. Solução salina e PTX foram administradas 1 hora após a indução da PA. Três horas após indução da PA os níveis de fator de necrose tumoral (TNF)-α no líquido peritoneal e os níveis séricos de interleucina (IL)-6 e IL-10 foram analisados pelo método de Enzima Imunoensaio (ELISA). A atividade da mieloperoxidase (MPO) foi analisada no pulmão e foram realizadas análises histológicas do pulmão e pâncreas, além do estudo da mortalidade. RESULTADOS: A administração de PTX 1 hora após a indução da PA reduziu significativamente os níveis de TNF-α peritoneal e os níveis séricos de IL-6 e IL-10 quando comparado ao grupo salina. Redução na mortalidade foi observado após o tratamento com PTX comparado ao grupo salina. CONCLUSÃO: A administração de PTX após a indução da PA diminuiu os níveis sistêmicos de citocinas pró-inflamatórias, sugerindo a possibilidade de que existe uma janela terapêutica para PTX após o início do PA.(AU)

Pretreatment with pentoxifylline attenuates lung injury induced by intestinal ischemia/reperfusion in rats / Pré-tratamento com pentoxifilina atenua a lesão pulmonar induzida por isquemia/reperfusão intestinal em ratos

PURPOSE: To investigate the protective effect of pentoxifylline against the lung injury observed after intestinal ischemia (I) followed by a period of reperfusion (R). METHODS: Twenty-eight male Wistar rats were equally divided into 4 experimental groups and operated under ketamine-xylazine anesthesia. (1) Sham: falsely-operated animals; (2) SS+IR: intestinal ischemia was accomplished by clipping the superior mesenteric artery during 60 minutes, with an administration of a standard volume of saline solution (SS) 5 min before the end of the ischemia period; the clip was then releases or a 120-min period of reperfusion; (3) I+PTX+R: ischemia as above, PTX was administered (25 mg/kg) and the gut reperfused as above; (4) PTX+I+PTX+R: Five minutes before arterial occlusion PTX was administered; the superior mesenteric artery was then clipped for 60 minutes. After 55-min ischemia, an additional dosis of PTX was administered; the clip was removed for reperfusion as above. At the 60th min of reperfusion a third dosis of PTX was administered. RESULTS: PTX markedly attenuated lung injury as manifested by significant decreases (all P<0.001 as compared with the SS+IR group) of pulmonary wet/dry tissue weight ratio, total protein content, myeloperoxidase activity and tumor necrosis factor-alpha. Moreover, it was apparent that in the group PTX+I+PTX+R the improvements have been even more significant. CONCLUSION: PTX exerted a protective effect on the lung from the injuries caused by intestinal ischemia/reperfusion.(AU)

OBJETIVO: Avaliar os efeitos protetores da pentoxifilina (PTX) na lesão pulmonar observada após isquemia (I) seguida de reperfusão (R) intestinal. MÉTODOS: Vinte e oito ratos machos foram divididos aleatoriamente em quatro grupos experimentais e operados sobre anestesia quetamina-xilazina. (1) Sham: animais falsamente operados; (2) SS+IR: isquemia intestinal realizada pelo clampeamento da artéria mesentérica superior durante 60 minutos, com a administração de solução salina (SS) 5 minutos antes do período de isquemia, após a retirada do clamp houve a reperfusão por mais 120 minutos; (3) I+PTX+R: isquemia como mencionado anteriormente seguida da administração de PTX (25 mg/Kg) 5 minutos antes do final da isquemia (60 minutos) seguida de reperfusão por mais 120 minutos; (4) PTX+I+PTX+R: 5 minutos antes da isquemia foi administrado PTX, após 55 minutos de isquemia foi administrado outra dose de PTX e a reperfusão mantida por mais 120 minutos, sendo que aos 60 minutos da reperfusão outra dose de PTX foi administrada. RESULTADOS: A pentoxifilina reduziu os marcadores de lesão pulmonar (proteínas totais, malondialdeído, atividade da mieloperoxidase e fator de necrose tumoral) quando comparada com o grupo não tratado (P<0.001), contudo esta redução foi mais significante no grupo PTX+I+PTX+R. CONCLUSÃO: A pentoxifilina exerce efeito protetor no pulmão no trauma causado por isquemia/reperfusão intestinal.(AU)