RESUMO
A 70-year-old woman who took a dietary supplement, Kin-toki Shoga(®) made from ginger for peripheral psychroesthesia and numbness, experienced an epigastric sense of incongruity and appetite loss and passed brown urine for 2 months. Although she had stopped taking the supplement, her symptoms had not improved. She was admitted to our hospital because of jaundice and liver dysfunction. After an investigation of causes, she was diagnosed with drug-induced liver injury caused by Kin-toki Shoga(®). Liver dysfunction gradually improved with conservative treatment. She was discharged on the 25th day of illness. Liver biopsy findings were compatible with drug-induced liver injury.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Suplementos Nutricionais/efeitos adversos , Zingiber officinale/efeitos adversos , Idoso , Biópsia , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico por imagem , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/terapia , Feminino , Humanos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
OBJECTIVES: Low-dose estrogen-progestin (LEP) agents are often used for relieving endometriosis-associated chronic pelvic pain, but a direct effect of LEP on endometriotic lesions remains to be demonstrated. The objective of this study is to investigate the antiproliferative and apoptotic effects of the synthetic progestin norethisterone (NET) against human endometriotic stromal cells (ESCs). STUDY DESIGN: Ovarian endometrioma specimens were obtained at laparoscopy from 19 patients with endometriosis, and ESCs were isolated. The antiproliferative effect of compounds against cultured ESCs was evaluated by measuring the inhibition of [(3)H]thymidine incorporation. The ability of compounds to induce apoptosis in the cultured cells was evaluated by the measurement of caspase 3/7 activity and by nuclear staining. The cytotoxicity of compounds was evaluated by measuring the leakage of lactate dehydrogenase (LDH) into the supernatant of the cell culture. RESULTS: NET and progesterone (P4) at concentrations of greater than 10nM significantly inhibited [(3)H]thymidine incorporation in a dose-dependent manner. Co-treatment with 17ß-estradiol at 0.1 ng/mL did not affect the inhibition of [(3)H]thymidine incorporation by NET. At concentrations greater than 100 nM, NET significantly increased caspase 3/7 activity and the numbers of apoptotic cells, whereas P4 did not. Treatment of ESCs for 24h with NET or P4 at concentrations of up to 1000 nM did not cause LDH leakage. CONCLUSIONS: NET inhibits the proliferation of ESCs and induces their apoptosis. These results suggest a possible direct effect of NET on endometriotic lesions in patients with endometriosis.
Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Anticoncepcionais Orais Sintéticos/uso terapêutico , Endometriose/tratamento farmacológico , Noretindrona/uso terapêutico , Adulto , Caspase 3/metabolismo , Caspase 7/metabolismo , Células Cultivadas , Anticoncepcionais Orais Sintéticos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Endométrio/citologia , Endométrio/efeitos dos fármacos , Endométrio/enzimologia , Feminino , Humanos , Noretindrona/farmacologia , Progesterona , Células Estromais/efeitos dos fármacos , Testes de Toxicidade , Adulto JovemRESUMO
AIMS: Ischemia-reperfusion injury is an important factor in the development of lower urinary tract symptoms (LUTS) that is partly mediated by the generation of free radicals. We investigate the effect of the phytotherapeutic agent Eviprostat, a treatment for benign prostatic hyperplasia (BPH) that has antioxidant and anti-inflammatory activity, on urinary bladder blood flow (BBF), and function in a rat model of bladder overdistension and emptying (OE). METHODS: For 8 days before surgery, OE rats received daily oral Eviprostat (36 mg/kg/day) or vehicle, while sham-operated animals received vehicle. The bladder was distended by infusion of saline over a period of 2 hr (overdistension) and then emptied. After 24 hr, BBF was measured with a laser speckle blood flow imager. The oxidative-stress marker malondialdehyde (MDA), proinflammatory cytokines, and myeloperoxidase were determined in the isolated bladder, and histological analysis was performed. Functional contractile responses of bladder strips to electrical field stimulation, carbachol, and KCl were measured. RESULTS: Twenty-four hours after bladder OE, a significant decrease in BBF and significant increases in bladder weight, malondialdehyde, proinflammatory cytokines, and myeloperoxidase were observed. Eviprostat almost completely prevented these changes. Histological analysis of the bladder of OE rats showed hemorrhage, accumulation of leukocytes, desquamation of epithelium, and edema, and Eviprostat suppressed these changes. The reduction in functional contractile forces in the bladder of OE rats was also prevented by Eviprostat. CONCLUSION: Eviprostat-mediated suppression of increased bladder oxidative stress and inflammation caused by bladder OE may contribute to the improvement of BBF and bladder function by Eviprostat.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Etamsilato/farmacologia , Extratos Vegetais/farmacologia , Obstrução do Colo da Bexiga Urinária/tratamento farmacológico , Bexiga Urinária/efeitos dos fármacos , Animais , Velocidade do Fluxo Sanguíneo , Citocinas/metabolismo , Modelos Animais de Doenças , Combinação de Medicamentos , Feminino , Mediadores da Inflamação/metabolismo , Fluxometria por Laser-Doppler , Malondialdeído/metabolismo , Contração Muscular/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Fitoterapia , Plantas Medicinais , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional , Fatores de Tempo , Bexiga Urinária/irrigação sanguínea , Bexiga Urinária/inervação , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Bexiga Urinária/fisiopatologia , Obstrução do Colo da Bexiga Urinária/metabolismo , Obstrução do Colo da Bexiga Urinária/patologia , Obstrução do Colo da Bexiga Urinária/fisiopatologiaRESUMO
OBJECTIVES: To clarify the mechanism by which chronic bladder ischemia causes bladder functional changes, and to investigate the involvement of oxidative stress and pro-inflammatory cytokines, and the effects of the phytotherapeutic drug, Eviprostat, on these biochemical marker levels and bladder function. METHODS: Male Sprague-Dawley rats aged 15 weeks were divided into three groups. Arterial injury was experimentally induced by balloon endothelial injury of the iliac arteries, and a 2% cholesterol diet was given for 8 weeks. Rats in the arterial-injury group were given daily oral vehicle or Eviprostat, whereas sham-operated animals on a regular diet (0.09% cholesterol) were given vehicle for the last 2 weeks. Eight weeks after surgery, the levels of bladder pro-inflammatory cytokines, as well as bladder and urinary oxidative-stress markers, were determined. Cystometrograms were carried out without anesthesia or restraint. RESULTS: Bladder and urinary oxidative-stress markers, and bladder pro-inflammatory cytokine levels were significantly increased in the arterial-injury group, and Eviprostat markedly suppressed these increase. The cystometrograms showed that arterial injury decreased the intermicturition interval without affecting the micturition pressure. This decrease was reversed by Eviprostat treatment. CONCLUSIONS: Oxidative stress and pro-inflammatory cytokines might be involved in the development of overactive bladder by atherosclerosis-induced chronic bladder ischemia. Eviprostat might provide an attractive treatment option for individuals with bladder dysfunction due to chronic bladder ischemia because of its anti-oxidant and anti-inflammatory properties.
Assuntos
Etamsilato/farmacologia , Etamsilato/uso terapêutico , Isquemia/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária/irrigação sanguínea , 8-Hidroxi-2'-Desoxiguanosina , Animais , Aterosclerose/complicações , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Combinação de Medicamentos , Interleucina-8/metabolismo , Isquemia/etiologia , Masculino , Malondialdeído/metabolismo , Modelos Animais , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , Bexiga Urinária/metabolismo , Bexiga Urinária/fisiopatologia , Bexiga Urinária Hiperativa/metabolismo , Micção/efeitos dos fármacos , Urodinâmica/efeitos dos fármacosRESUMO
BACKGROUND: Anti-inflammatory medications have been used for the treatment of chronic prostatitis. The phytotherapeutic agent Eviprostat, a popular treatment for benign prostatic hyperplasia in Japan and Germany, has antioxidant and anti-inflammatory activity. We investigated the effects of the phytotherapeutic agent Eviprostat on prostate inflammation induced in castrated rats by the injection of 17beta-estradiol. METHODS: Ten-month-old male Wistar rats were divided into five groups. Nonbacterial prostatitis was experimentally induced in groups 2-5 by castration followed by daily subcutaneous injection of 17beta-estradiol for 30 days. The rats were orally administered 0.1% Tween-80 (group 2), low-dose Eviprostat (group 3), high-dose Eviprostat (group 4), or cernitin pollen extract (group 5) for the last 2 weeks of 17beta-estradiol administration. Sham-operated rats (group 1) were orally administered 0.1% Tween-80. On the 31st day after surgery, the weight of the prostate and the levels of prostatic proinflammatory cytokines as well as the oxidative-stress marker malondialdehyde were determined and histological alterations noted. RESULTS: Experimentally induced nonbacterial prostatitis led to a significant decrease in prostate weight and increases in malondialdehyde and proinflammatory cytokine levels. Eviprostat significantly suppressed the increases in malondialdehyde and cytokine levels without affecting prostate weight. Histologically, nonbacterial prostatitis was evident in the lateral lobe of the prostate, and Eviprostat treatment significantly suppressed the severity of the lesion. CONCLUSIONS: Eviprostat, which has effective antioxidant and anti-inflammatory activities in the prostate, may be useful for the clinical treatment of chronic prostatitis. These activities of Eviprostat may also contribute to the amelioration of prostate inflammation in BPH patients. Prostate 69: 1404-1410, 2009. (c) 2009 Wiley-Liss, Inc.
Assuntos
Etamsilato/farmacologia , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Hiperplasia Prostática/tratamento farmacológico , Prostatite/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Modelos Animais de Doenças , Combinação de Medicamentos , Estradiol/toxicidade , Masculino , Orquiectomia , Tamanho do Órgão , Estresse Oxidativo/efeitos dos fármacos , Próstata/efeitos dos fármacos , Próstata/patologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/patologia , Prostatite/induzido quimicamente , Prostatite/patologia , Ratos , Ratos WistarRESUMO
PURPOSE: Ischemia/reperfusion injury is a major etiological factor in the progression of bladder dysfunction after partial bladder outlet obstruction and it is partly mediated by the generation of free radicals. The phytotherapeutic agent Eviprostat, a popular treatment for benign prostatic hyperplasia in Japan and Germany, has antioxidant and anti-inflammatory activity. We investigated the effect of Eviprostat on oxidative stress and inflammation in bladder dysfunction in a bladder outlet obstruction rat model. MATERIALS AND METHODS: Bladder outlet obstruction was surgically induced in male rats by placing a rubber ring around the urethra. Rats with bladder outlet obstruction were administered daily oral Eviprostat or vehicle, while sham operated animals were treated with vehicle. On day 6 after surgery bladder weight, oxidative stress markers and proinflammatory cytokine levels as a measure of bladder inflammation, were determined and histological alterations noted. Functional contractility studies were performed with longitudinal bladder strips. RESULTS: Bladder outlet obstruction led to a significant increase in bladder weight, oxidative stress markers and proinflammatory cytokine levels. Eviprostat significantly suppressed these increases without affecting bladder weight. Histological analysis showed increased detrusor muscle hypertrophy and increased numbers of collagen fibers with accompanying inflammatory infiltration in the bladder of vehicle treated bladder outlet obstruction animals. Eviprostat treatment was associated with suppression of these changes. Decreased responses of obstructed bladder strips to electrical stimulation and KCl were ameliorated by Eviprostat treatment. CONCLUSIONS: Eviprostat mediated decrease of the increased oxidative stress and bladder inflammation caused by bladder outlet obstruction may contribute to the protection of bladder function.