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1.
Int. j. morphol ; 41(5): 1537-1549, oct. 2023. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1521025

RESUMO

SUMMARY: Cisplatin (Cis) is an important chemotherapeutic agent used in cancer treatment. Males exposed to Cis were reported to exhibit testicular toxicity. Cis-induced testicular toxicity is mediated by oxidative stress, inflammation, testosterone inhibition and apoptosis. Accordingly, this study was conducted to evaluate the potential protective roles of infliximab (IFX), which is an anti- TNF-a agent, and of white tea (Camellia sinensis), which is known to possess antioxidant, anti-apoptotic, and anti-inflammatory effects, against Cis-induced testicular toxicity in rats. Rats were randomly assigned into five groups as follows: control group, Cisplatin (7 mg/kg) treatment group, Cisplatin (7 mg/kg) + infliximab (7 mg/kg) treatment group, cisplatin + white tea (WT) treatment group, and Cisplatin+ WT+IFX combined treatment group. In the present study, Cis exposure reduced the sperm count. It also increased testicular oxidative stress as well as the levels of inflammatory and apoptotic markers. Histopathological assays supported the biochemical findings. Treatment with IFX and/or WT restored testicular histology, preserved spermatogenesis, suppressed oxidative stress and apoptosis, and significantly ameliorated Cis-induced damage. It was concluded that white tea and infliximab could potentially serve as therapeutic options for the protection of testicular tissue against the harmful effects of Cis.


El cisplatino (Cis) es un importante agente quimioterapéutico utilizado en el tratamiento del cáncer. Se informó que los hombres expuestos a Cis exhibieron toxicidad testicular. La toxicidad testicular inducida por Cis está mediada por el estrés oxidativo, la inflamación, la inhibición de la testosterona y la apoptosis. En consecuencia, este estudio se realizó para evaluar las posibles funciones protectoras de infliximab (IFX), un agente anti-TNF-α, y del té blanco (Camellia sinensis), conocido por sus propiedades antioxidantes, antiapoptóticas y anti-TNF-α -efectos inflamatorios, contra la toxicidad testicular inducida por Cis en ratas. Cinco grupos de ratas se asignaron al azar de la siguiente manera: grupo control, grupo de tratamiento con cisplatino (7 mg/ kg), grupo de tratamiento con cisplatino (7 mg/kg) + infliximab (7 mg/kg), grupo de tratamiento con cisplatino + té blanco (WT), y grupo de tratamiento combinado Cisplatino+ WT+IFX. En el presente estudio, la exposición a Cis redujo el conteo de espermatozoides. También aumentó el estrés oxidativo testicular, así como los niveles de marcadores inflamatorios y apoptóticos. Los ensayos histopatológicos respaldaron los hallazgos bioquímicos. El tratamiento con IFX y/o WT restauró la histología testicular, preservó la espermatogénesis, suprimió el estrés oxidativo y la apoptosis, y mejoró significativamente el daño inducido por Cis. Se concluyó que el té blanco y el infliximab podrían potencialmente servir como opciones terapéuticas para la protección del tejido testicular contra los efectos nocivos de Cis.


Assuntos
Animais , Masculino , Ratos , Chá/química , Testículo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Cisplatino/toxicidade , Camellia sinensis/química , Infliximab/farmacologia , Contagem de Espermatozoides , Testículo/patologia , Imuno-Histoquímica , Extratos Vegetais/química , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ratos Sprague-Dawley , Apoptose , Estresse Oxidativo , Glutationa/análise , Inflamação , Malondialdeído/análise
2.
Radiat Environ Biophys ; 62(3): 395-402, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37410120

RESUMO

Although radiotherapy is widely employed in the treatment of various malignancies in oncology patients, its use is limited by the toxic effects it causes in surrounding tissues, including the gastrointestinal system. Korean Red Ginseng (KRG) is a traditional drug reported to possess antioxidant and restorative properties in various studies. The purpose of the present study was to investigate the protective effects of KRG against radiation-associated small intestinal damage. Twenty-four male Sprague Dawley rats were randomly assigned into three groups. No procedure was performed on Group 1 (control) during the experiment, while Group 2 (x-irradiation) was exposed to radiation only. Group 3 (x-irradiation + ginseng) received ginseng via the intraperitoneal route for a week prior to x-irradiation. The rats were killed 24 h after radiation. Small intestinal tissues were evaluated using histochemical and biochemical methods. An increase in malondialdehyde (MDA) levels and a decrease in glutathione (GSH) were observed in the x-irradiation group compared to the control group. KRG caused a decrease in MDA and caspase-3 activity and an increase in GSH. Our findings show that it can prevent damage and apoptotic cell death caused by x-irradiation in intestinal tissue and can therefore play a protective role against intestinal injury in patients receiving radiotherapy.


Assuntos
Panax , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Panax/química , Panax/metabolismo , Intestinos , Antioxidantes/farmacologia , Glutationa/metabolismo
3.
Hum Exp Toxicol ; 41: 9603271221143029, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36455263

RESUMO

This study aimed to elucidate the effects of amifostine (ethyol) (AM), a synthetic radioprotector, and red ginseng (RG), a natural radioprotective agent, against the toxic effect of ionizing radiation (IR) on kidney tissues through changes in biochemical and histopathological parameters in addition to contributions to the use of amifostine and RG in clinical studies. Five groups were established: Group I (control, receiving only saline by gavage), Group II (IR only), and Group III (IR+AM, 200 mg/kg intraperitoneally (i.p.). Group IV (IR + RG, 200 mg/kg orally once a day for 4 weeks), and Group V (IR+RG+AM, 200 mg/kg orally once/day for 4 weeks before IR and 200 mg/kg AM administered (i.p.) 30 min before IR). All groups, except for the control group, were subject to 6-Gy whole-body IR in a single fraction. 24 h after irradiation, all animals were sacrificed under anesthesia. IR enhanced MDA, 8-OHdG, and caspase-3 expression while decreasing renal tissue GSH levels (p < .05). Significant numbers of necrotic tubules together with diffuse vacuolization in proximal and distal tubule epithelial cells were also observed. The examination also revealed substantial brush boundary loss in proximal tubules as well as relatively unusual glomerular structures. While GSH levels significantly increased in the AM, RG, and AM+RG groups, a decrease in KHDS, MDA, 8-OHdG, and caspase-3 expression was observed, compared to the group subject to IR only (p < .05). Therefore, reactive oxygen species-scavenging antioxidants may represent a promising treatment for avoiding kidney damage in patients receiving radiation.


Assuntos
Amifostina , Panax , Animais , Amifostina/farmacologia , Amifostina/uso terapêutico , Caspase 3 , Rim , Radiação Ionizante , 8-Hidroxi-2'-Desoxiguanosina
4.
Eur Cytokine Netw ; 32(2): 31-38, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34369381

RESUMO

BACKGROUND: Obesity and dyslipidemia due to estrogen deficiency are among the important health problems in menopausal women. Increasing evidence reports the anti-obesity and anti-hyperlipidemic properties of tea polyphenols. However, the effect of white tea (WT) with high polyphenol content on overweight and lipid profile is uncertain. Here, we aimed to examine the effects of long-term WT consumption on serum leptin, tumor necrosis factor- alpha (TNF-α) and uncoupling protein 1 (UCP1) mRNA gene expression in ovariectomized (OVX) rats. METHODS: Adult rats were divided into four groups (n = 8): (i) sham, (ii) OVX, (iii) WT and (iv) OVX + WT. WT was given at a dose of 0.5% w/v for 12 weeks. In the study, body weight, serum leptin, TNF, estradiol (E2) levels, lipid profile and UCP1 mRNA gene expression in brown adipose tissue (BAT) were evaluated. RESULTS: There was a significant increase in body weight of OVX rats, which was decreased following WT consumption. While leptin and E2 levels decreased in the OVX group, TNF levels increased. There was no difference between the NF-kB levels of the groups. In addition, BAT UCP1 mRNA expression was significantly decreased in OVX groups, while WT treatment stimulated UCP1 activity. CONCLUSION: We explain the stimulatory effect of WT on weight loss mainly by the induction of UCP1 gene-mediated thermogenesis and suppression of inflammation. Therefore, we suggest that prolonged WT consumption may have beneficial effects in limiting excess weight gain caused by estrogen deficiency.


Assuntos
Biomarcadores , Comportamento de Ingestão de Líquido , Leptina/sangue , Chá , Fator de Necrose Tumoral alfa/sangue , Proteína Desacopladora 1/sangue , Animais , Peso Corporal , Feminino , Expressão Gênica , Avaliação do Impacto na Saúde , Metabolismo dos Lipídeos , Ovariectomia , Ratos , Chá/química , Fatores de Tempo
5.
Braz J Cardiovasc Surg ; 35(4): 512-520, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32864932

RESUMO

INTRODUCTION: Ischemia-associated mortality caused by aortic cross-clamps, as in ruptured abdominal aorta aneurysm surgeries, and reperfusion following their removal represent some of the main emergency conditions in cardiovascular surgery. The purpose of our study was to examine the potential protective effect of tea grape against aortic occlusion-induced lung injury using biochemical, histopathological, immunohistochemical, and quantitative analyses. METHODS: Thirty-two male Sprague-Dawley rats were randomly assigned into four groups: control (healthy), glycerol + ischemia/reperfusion (I/R) (sham), I/R, and I/R + tea grape. RESULTS: Following aortic occlusion, we observed apoptotic pneumocytes, thickening in the alveolar wall, edematous areas in interstitial regions, and vascular congestion. We also observed an increase in pulmonary malondialdehyde (MDA) levels and decrease in pulmonary glutathione (GSH). However, tea grape reduced apoptotic pneumocytes, edema, vascular congestion, and MDA levels, while increased GSH levels in lung tissue. CONCLUSION: Our findings suggest that tea grape is effective against aortic occlusion-induced lung injury by reducing oxidative stress and apoptosis.


Assuntos
Lesão Pulmonar , Traumatismo por Reperfusão , Vitis , Animais , Aorta Abdominal/cirurgia , Pulmão , Lesão Pulmonar/etiologia , Lesão Pulmonar/prevenção & controle , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/prevenção & controle , Chá
6.
Rev. bras. cir. cardiovasc ; 35(4): 512-520, July-Aug. 2020. tab, graf
Artigo em Inglês | LILACS, SES-SP | ID: biblio-1137306

RESUMO

Abstract Introduction: Ischemia-associated mortality caused by aortic cross-clamps, as in ruptured abdominal aorta aneurysm surgeries, and reperfusion following their removal represent some of the main emergency conditions in cardiovascular surgery. The purpose of our study was to examine the potential protective effect of tea grape against aortic occlusion-induced lung injury using biochemical, histopathological, immunohistochemical, and quantitative analyses. Methods: Thirty-two male Sprague-Dawley rats were randomly assigned into four groups: control (healthy), glycerol + ischemia/reperfusion (I/R) (sham), I/R, and I/R + tea grape. Results: Following aortic occlusion, we observed apoptotic pneumocytes, thickening in the alveolar wall, edematous areas in interstitial regions, and vascular congestion. We also observed an increase in pulmonary malondialdehyde (MDA) levels and decrease in pulmonary glutathione (GSH). However, tea grape reduced apoptotic pneumocytes, edema, vascular congestion, and MDA levels, while increased GSH levels in lung tissue. Conclusion: Our findings suggest that tea grape is effective against aortic occlusion-induced lung injury by reducing oxidative stress and apoptosis.


Assuntos
Animais , Masculino , Ratos , Traumatismo por Reperfusão/prevenção & controle , Vitis , Lesão Pulmonar/etiologia , Lesão Pulmonar/prevenção & controle , Aorta Abdominal/cirurgia , Chá , Ratos Sprague-Dawley , Pulmão
7.
Cells Tissues Organs ; 209(1): 64-74, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32564021

RESUMO

Osteoporosis is an important skeletal disease characterized by bone weakness and high risk of fracture in postmenopausal women. Tea consumption is known to play an important role in the prevention or alleviation of osteoporosis. However, the therapeutic effects of aqueous extracts of white tea (WT) have not been evaluated in osteoporosis rat models. The aim of this study was to investigate the potential anti-osteoporotic role of WT in ovariectomized (OVX) rats. WT was given orally at 0.5% w/v doses for 12 weeks in OVX rats. Biochemical parameters in blood samples, bone tartrate-resistant acid phosphatase (TRAP), C-terminal telopeptide of type 1 collagen (CTX) and estradiol levels were evaluated. Bone mineral density and bone mineral content values were measured in the left femur. In addition to histopathological examination, osteolcalcin, osteopontin and TUNEL levels were determined. OVX group data demonstrated that bone loss occurred by thinning of the metaphyseal growth plates of the femur. Similarly, the levels of TRAP and CTX, markers of osteoclastic activity, were found to be high concurrently with a decrease in femoral bone mineral density. In addition, increased osteolcalcin and osteopontin levels were present in the metaphyseal growth zones. On the other hand, while TRAP and CTX levels were suppressed in the OVX-WT group, bone mineral content increased. In ad-dition, TUNEL, osteocalcin and osteopontin positivity decreased in the right femoral metaphysis growth zones, proliferating zone and resting zone cells. These results showed that chronic WT consumption has a protective effect by reducing bone resorption in OVX-induced osteoporotic rats.


Assuntos
Complexo Mediador/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Ovariectomia/efeitos adversos , Chá/química , Animais , Modelos Animais de Doenças , Feminino , Humanos , Ratos , Ratos Sprague-Dawley
8.
Ear Nose Throat J ; 98(6): E64-E69, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31032661

RESUMO

Radiotherapy is a method of treatment used on malignant head and neck tumors; however, it may lead to adverse effects by influencing other tissues because its effects are not specific to tumor tissues. These adverse effects limit the effectiveness of the treatment and sometimes lead to termination of the treatment. This study aims to histopathologically and biochemically investigate the protective effect of whortleberry against the cellular degeneration and oxidative stress that take place in salivary glands due to radiotherapy. The rats were divided into 6 groups. One group was given radiotherapy only, one group was given radiotherapy and 100 mg/kg of whortleberry, and one group was given radiotherapy and 200 mg/kg of whortleberry. The remaining 3 groups were designated as whortleberry, sham, and control groups. At the end of the study, samples collected were histopathologically and biochemically analyzed. In the group given radiotherapy only, acinar areas were reduced histopathologically, whereas ductal areas increased (P < .01). Oxidative stress increased only in the group given radiotherapy, whereas the oxidative stress levels in the other groups were close to those in the control groups. In conclusion, whortleberry reduces cellular degeneration and oxidative stress that take place in salivary glands due to radiotherapy.


Assuntos
Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Extratos Vegetais/farmacologia , Glândula Submandibular/efeitos dos fármacos , Glândula Submandibular/efeitos da radiação , Vaccinium myrtillus , Animais , Masculino , Pescoço , Radiação Ionizante , Radioterapia Conformacional , Ratos , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/metabolismo , Glândulas Salivares/efeitos da radiação , Glândula Submandibular/metabolismo
9.
Biomed Pharmacother ; 112: 108604, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30798139

RESUMO

OBJECTIVE: Nephrotoxicity is the most important side effect of the antineoplastic drug cisplatin, thereby restricting its use. The aim of this study was to investigate the protective effects of white tea infusions (WT) against renal damage induced by cisplatin (CP) in rats by biochemical and histopathological means. MATERIALS AND METHODS: This study used 24 female Sprague Dawley rats at 12-14 weeks of age and weighing 250-300 g. Rats were divided into three groups: Control, CP and CP + WT groups. CP was injected 7 mg/kg i.p as a single dose/rat in the CP group. White tea was given at a dose of 0.5% (w/v) for 4 weeks. At the end of the experiment, blood urea nitrogen (BUN), creatinine, uric acid, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nuclear factor kappa B (NF-κB) along with caspase-3 in the kidney were evaluated in study. RESULTS: BUN, creatinine, TNF-α, NF-κB and IL-6 levels of the CP group showed a statisically significant increase in comparison to the control group. TNF-α, NF-κB and IL-6 levels showed a statistically significant decrease in the CP + WT group with respect to the CP group. Caspase-3 levels in tubular epithelial cells decreased in CP + WT group compared with CP group (p = 0.02). CONCLUSION: White tea infusions reduced significantly the nephrotoxicity of CP. The anti-nephrotoxic feature of the infusion may be attributed primarily to its anti-inflammatory and anti-apoptotic characteristics.


Assuntos
Injúria Renal Aguda/sangue , Injúria Renal Aguda/dietoterapia , Cisplatino/toxicidade , NF-kappa B/sangue , Chá , Fator de Necrose Tumoral alfa/sangue , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Animais , Antineoplásicos/toxicidade , Biomarcadores/sangue , Feminino , Ratos , Ratos Sprague-Dawley
10.
Braz. j. otorhinolaryngol. (Impr.) ; 85(1): 55-62, Jan.-Feb. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-984047

RESUMO

Abstract Introduction: Cisplatin is one of the main chemotherapeutic agents used for the treatment of many types of cancer. However, ototoxicity, one of the most serious side effects of cisplatin, restricts its usage. Objective: We aimed to investigate the protective effects of whortleberry extract against cisplatin-induced ototoxicity by evaluating hearing and histopathological cochlear damage and by measuring the biochemical parameters affected byoxidative stress. Methods: Forty-eight male rats were included in the study after performing Distortion Product Otoacoustic Emission test to confirm that their hearing levels were normal. The rats were randomly divided into six groups: the control group, the sham group, and, which received only whortleberry extract, only cisplatin, cisplatin + 100 mg whortleberry extract, cisplatin + 200 mg whortleberry extract, respectively. Audiologic investigation was performed by performing the Distortion Product Otoacoustic Emission test at the beginning and at the eighth day of the study. Cardiac blood samples were collected for biochemical analysis, and the rats were sacrificed to obtain cochlear histopathological specimens on the eighth day. Results: The results revealed that whortleberry protects hearing against cisplatin-induced ototoxicity independent of the dose. However, high doses of whortleberry extract are needed to prevent histopathological degeneration and oxidative stress. Conclusion: The results obtained in this study show that whortleberry extract has a protective effect against cisplatin-induced ototoxicity.


Resumo Introdução: A cisplatina é um dos principais agentes quimioterápicos utilizados para o tratamento de muitos tipos de câncer. No entanto, a ototoxicidade, um dos efeitos colaterais mais graves da cisplatina, restringe seu uso. Objetivo: Nosso objetivo foi investigar os efeitos protetores do extrato de uva-do-monte contra a ototoxicidade induzida por cisplatina, avaliar o dano auditivo e histopatológico coclear e medir os parâmetros bioquímicos afetados pelo estresse oxidativo. Método: Foram incluídos no estudo 48 ratos machos após teste de emissão otoacústica evocada por produto de distorção para confirmar que seus níveis de audição eram normais. Os ratos foram divididos aleatoriamente em seis grupos: o grupo controle, o grupo simulado, o que recebeu apenas extrato de uva-do-monte, o que recebeu apenas cisplatina, o que recebeu cisplatina + 100 mg de extrato de uva-do-monte e o que recebeu cisplatina + 200 mg de extrato de uva-do-monte, respectivamente. A investigação audiológica foi feita através do teste de emissão otoacústica de produto de distorção no início e no oitavo dia do estudo. As amostras de sangue cardíaco foram coletadas para análise bioquímica e os ratos foram sacrificados para obtenção de espécimes histopatológicos cocleares no oitavo dia. Resultados: Os resultados revelaram que o extrato de uva-do-monte protege a audição contra a ototoxicidade induzida por cisplatina, independentemente da dose. No entanto, são necessárias doses elevadas do extrato para evitar a degeneração histopatológica e o estresse oxidativo. Conclusão: Os resultados obtidos neste estudo mostram que o extrato de uva-do-monte tem um efeito protetor contra a ototoxicidade induzida por cisplatina.


Assuntos
Animais , Masculino , Cisplatino/toxicidade , Cóclea/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Audição/efeitos dos fármacos , Antocianinas/uso terapêutico , Antineoplásicos/toxicidade , Valores de Referência , Estimulação Acústica , Distribuição Aleatória , Reprodutibilidade dos Testes , Resultado do Tratamento , Ratos Wistar , Emissões Otoacústicas Espontâneas/efeitos dos fármacos , Cóclea/patologia , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/uso terapêutico
11.
Braz J Otorhinolaryngol ; 85(1): 55-62, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29174583

RESUMO

INTRODUCTION: Cisplatin is one of the main chemotherapeutic agents used for the treatment of many types of cancer. However, ototoxicity, one of the most serious side effects of cisplatin, restricts its usage. OBJECTIVE: We aimed to investigate the protective effects of whortleberry extract against cisplatin-induced ototoxicity by evaluating hearing and histopathological cochlear damage and by measuring the biochemical parameters affected byoxidative stress. METHODS: Forty-eight male rats were included in the study after performing Distortion Product Otoacoustic Emission test to confirm that their hearing levels were normal. The rats were randomly divided into six groups: the control group, the sham group, and, which received only whortleberry extract, only cisplatin, cisplatin+100mg whortleberry extract, cisplatin+200mg whortleberry extract, respectively. Audiologic investigation was performed by performing the Distortion Product Otoacoustic Emission test at the beginning and at the eighth day of the study. Cardiac blood samples were collected for biochemical analysis, and the rats were sacrificed to obtain cochlear histopathological specimens on the eighth day. RESULTS: The results revealed that whortleberry protects hearing against cisplatin-induced ototoxicity independent of the dose. However, high doses of whortleberry extract are needed to prevent histopathological degeneration and oxidative stress. CONCLUSION: The results obtained in this study show that whortleberry extract has a protective effect against cisplatin-induced ototoxicity.


Assuntos
Antocianinas/uso terapêutico , Antineoplásicos/toxicidade , Cisplatino/toxicidade , Cóclea/efeitos dos fármacos , Audição/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Estimulação Acústica , Animais , Antioxidantes/uso terapêutico , Cóclea/patologia , Masculino , Emissões Otoacústicas Espontâneas/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais , Distribuição Aleatória , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Razão Sinal-Ruído , Resultado do Tratamento , Vaccinium myrtillus
12.
Ren Fail ; 40(1): 466-474, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30130136

RESUMO

PURPOSE: This study investigated the antioxidant effects of whortleberry against cisplatin-induced nephrotoxicity in rats. MATERIAL AND METHODS: This study included 48 female Sprague-Dawley rats weighing 263.68 ± 8.29 g. The rats were divided into the following six groups, with eight rats in each group: control, ethanol control, whortleberry control, cisplatin control, 16 mg/kg cisplatin +100 mg/kg whortleberry, and 16 mg/kg cisplatin +200 mg/kg whortleberry groups. Biochemical analysis was performed by measuring total oxidant status and total antioxidant status, histopathological analysis was performed by calculating proximal and distal tubule areas (µm2), and immunohistochemical analysis was performed by determining anti-Caspase-3 immunostaining. Differences among the groups were examined using one-way analysis of variance, and p < .05 was considered statistically significant. RESULTS: Cisplatin treatment decreased the total antioxidant status and increased the total oxidant status and Caspase-3 level. Moreover, it resulted in the dilatation, vacuolization and loss of tubular epithelial cells; and glomerular degeneration and edema in the kidney tissues (p < .05). Treatment with 100 and 200 mg whortleberries increased the total antioxidant status; decreased the total oxidant status and Caspase-3 level and ameliorated distal and proximal tubule degeneration, glomerular degeneration and edema in the kidney tissues (p < .05). CONCLUSIONS: Our results indicate that the antioxidant effects of the whortleberry decrease cisplatin-associated nephrotoxicity.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Cisplatino/toxicidade , Extratos Vegetais/farmacologia , Vaccinium myrtillus/química , Injúria Renal Aguda/patologia , Animais , Antineoplásicos/toxicidade , Antioxidantes/metabolismo , Feminino , Rim/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
13.
Naunyn Schmiedebergs Arch Pharmacol ; 391(9): 915-931, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29860655

RESUMO

Despite the enormous advances made in the field of oncology, no solution to the side effect of nephrotoxicity caused by cisplatin used as an antineoplastic agent for approximately 40 years has yet been discovered. This study investigated the effects of cisplatin on the kidney, the damage mechanism involved, and the potential capacity of agents such as amifostine, curcumin, and melatonin to elicit a future therapeutic protocol in cisplatin-induced nephrotoxicity at the ultrastructural and molecular levels. Our study consisted of five groups: control (saline solution only; group 1), cisplatin (cisplatin only; group 2), cisplatin + amifostine (group 3), cisplatin + curcumin (group 4), and cisplatin + melatonin (group 5). Rats in all groups except the control group were administered a single intraperitoneal dose of 7.5 mg/kg cisplatin. All animals were sacrificed under anesthesia on the sixth day after cisplatin administration. Cisplatin increased serum urea and serum creatinine levels and caused an increase in tubular necrosis scores (TNS), HPS, NF-κB/p65, 8-OHdG, and caspase-3 expressions (p < 0.05). Additionally, we observed basal membrane thickening in glomerules, intense electron deposition in the subendothelial region, and atypical folds in podocyte pedicels. Amifostine, curcumin, and melatonin reduced the increases in serum urea and serum creatinine levels following cisplatin administration and reduced the levels of TNS, HPS, NF-κB/p65, 8-OHdG, and caspase-3 expressions (p < 0.05). ROS-scavenging antioxidants may be a promising means of preventing acute kidney disease in patients using cisplatin in the treatment of malignant tumors.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Amifostina/uso terapêutico , Antioxidantes/uso terapêutico , Curcumina/uso terapêutico , Melatonina/uso terapêutico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Animais , Antineoplásicos , Cisplatino , Masculino , Ratos Sprague-Dawley
14.
Artigo em Inglês | MEDLINE | ID: mdl-29018487

RESUMO

We explored the effects of topical curcumin on the healing of nasal mucosal wounds. A total of 32 Sprague-Dawley Albino rats were randomized in equal numbers into four groups, and unilateral nasal wounds were created using an interdental brush. Group 1 (the sham-control group) contained untreated rats with traumatized right-side nasal cavities; Group 2 and 3 rats were similarly traumatized and treated with topical curcumin (5 and 10 mg/mL) dissolved in dimethyl sulfoxide daily for 7 days after trauma; Group 4 rats were treated with topical dimethyl sulfoxide only. All rats were decapitated on day 15 and the healing sites evaluated by blinded observers in terms of the presence of cellular hyperplasia, goblet cell hypertrophy and degeneration, leucocytic infiltration, ciliary loss and degeneration, edema, and vascular dilation. On histopathological evaluation, all of cellular hyperplasia, leukocytic infiltration, and edema were significantly reduced in Group 3 compared with Group 1 (p = 0.001, p = 0.004, and p = 0.008, resp.). Thus, curcumin reduced the inflammatory response and significantly accelerated wound healing.

15.
Arch Bronconeumol ; 51(11): 551-7, 2015 Nov.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-26071367

RESUMO

INTRODUCTION: Methotrexate (MTX) is used to treat cancers, several forms of arthritis and other rheumatic conditions, although MTX may cause pulmonary toxicity related to the production of free oxygen radicals, various cytokines. Infliximab (IB) with its potent effect on tumor necrosis factor-alpha (TNF-α) inhibition also inhibits the release of endothelin-1 (ET-1). We aimed to investigate whether IB reduces pulmonary damage induced by an overdose of MTX. METHOD: The rats were divided into 3 groups of 8 animals. The control group was given only saline. One dose of 20mg/kg MTX intraperitoneal was administered in the MTX group. IB 7 mg/kg was given to the MTX+IB (MI) group. Three days after IB was administered, 20mg/kg MTX was given. Five days after MTX was administered, all rats were sacrificed. RESULTS: The TNF-α, ET-1, malondialdehyde (MDA), myeloperoxidase (MPO) and caspase-3 levels in MTX group were significantly higher than in control groups of TNF-α (P=.001), ET-1 (P=.001), MDA (P=.001), MPO (P=.001) and caspase-3 levels (P=.001) and MI groups of TNF-α (P=.009), ET-1 (P=.001), MDA (P=.047), MPO (P=.007) and caspase-3 levels (P=.003). The MI group had less histopathological damage in lung tissue than the MTX group. CONCLUSION: Overdose of MTX leads to cytokine release and the formation of reactive oxygen species in addition to increased ET-1 secretion release that causes lung damage. IB, as a potent proinflammatory agent, TNF-α blocker, can decrease ET-1 release and oxidative stress, it may show significant protective effects in lung tissue against damage caused by MTX overdose.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Anti-Inflamatórios/uso terapêutico , Infliximab/uso terapêutico , Metotrexato/efeitos adversos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/análise , Avaliação Pré-Clínica de Medicamentos , Endotelina-1/análise , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/análise , Infiltração de Neutrófilos , Peroxidase/análise , Alvéolos Pulmonares/patologia , Distribuição Aleatória , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/antagonistas & inibidores
16.
Eur J Cardiothorac Surg ; 44(5): e332-40, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23946499

RESUMO

OBJECTIVES: Hyperbaric oxygen (HBO) has been shown to be effective in preventing neurological injuries in animal models of ischaemia, whereas iloprost (IL) prevents ischaemia-related mitochondrial dysfunction and reduces infarction size after focal cerebral ischaemia in animal models. The aim of the present study was to investigate the effect of combined HBO and IL treatment on spinal cord ischaemia-reperfusion (IR) injury by neurological, histopathological and biochemical methods in an experimental study. METHODS: Eighty New Zealand white male rabbits were randomly allocated into one of five study groups. The HBO group received a single session of HBO treatment and the IL group received an infusion of 25 ng/kg/min IL; the HBO + IL group received both HBO and IL and the control group received only 0.9% saline; the fifth group was the sham group. Levels of S100ß protein, neuron-specific enolase (NSE) and nitric oxide (NO) were measured at onset, at the end of ischaemia period and at the 24th and 48th hour of reperfusion. Physical activity was assessed using Tarlov criteria 24, and the spinal cords of the sacrificed rabbits were evaluated histopathologically. Additionally, tissue malondialdehyde (MDA) and antioxidant enzyme activities [total superoxide dismutase (SOD); catalase (CAT) and glutathione peroxidase (GSH-Px) were assessed. RESULTS: Neurological scores in the HBO, IL and HBO + IL groups were statistically significantly better compared with the control group at the 24th (P = 0.001 for all) and 48th hour (P = 0.001 for all). Histopathological scores in the HBO, IL and HBO + IL groups were also significantly better compared with the control group (P = 0.003, 0.001 and 0.001, respectively). Whereas MDA, NSE, S100ß protein and NO concentrations were significantly lower, CAT and GSH-PX levels were significantly higher in either sham or treatment groups compared with the control group. CONCLUSIONS: Since we demonstrated beneficial effects on spinal cord IR injury, we think that both HBO and IL, either alone or in combination, may be reasonable in the treatment of IR injury. Furthermore, there did not appear to be synergistic effects with combined treatment. More research is needed for practical application in humans, following thoracoabdominal aortic surgery.


Assuntos
Oxigenoterapia Hiperbárica/métodos , Iloprosta/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Isquemia do Cordão Espinal/terapia , Vasodilatadores/uso terapêutico , Animais , Células do Corno Anterior/patologia , Antioxidantes/metabolismo , Hemodinâmica , Masculino , Óxido Nítrico/sangue , Coelhos , Distribuição Aleatória , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/patologia , Resultado do Tratamento
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