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柑橘胚性愈伤组织中四倍体变异细胞的凋亡研究
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3秒自动关闭窗口PMCID: PMC2704667Reduction of Amphotericin B-Induced Renal Tubular Apoptosis by N-Acetylcysteine ,1,* ,1 ,2 ,3 ,1 ,1 and
1*Corresponding author. Mailing address: Marmara University Hospital, Department of Infectious Diseases, Tophanelioglu caddesi, Altunizade, Istanbul, Turkey. Phone and fax: 90 216 3274142. E-mail:
This article has been
other articles in PMC.The reduction of amphotericin B (AmB)-induced renal tubular apoptosis and nephrotoxicity by N-acetylcysteine (NAC) in a murine model was evaluated. Four groups of rats were treated with AmB for 5 days, and each group concomitantly received two doses of 30, 60, or 120 mg of NAC/kg of body weight/day or sterile water for 5 days. Groups that received concomitant NAC at any dose had significantly decreased levels of apoptosis compared to that in animals receiving AmB only (48.8% versus 27.4, 23.6, or 23.5%, P < 0.001).Photomicrographs of renal tubular cells (at a magnification of ×400). Apoptotic cells were detected immunohistochemically by in situ end labeling of DNA strand breaks (TUNEL assay). All dark-stained cells (white arrows) are apoptotic. (Left) Tubular ...Average AIs for animal groupsaThe use of NAC for the prevention of the radiocontrast agent-induced nephrotoxicity led us to evaluate the efficacy of NAC in the prevention of AmB-induced apoptosis and renal injury (, ). NAC is usually administered orally at 600 mg twice daily on the day before and the day of administration of the contrast agent. However, in some studies, the intravenous form of the drug has been used in doses as high as 50 mg/kg (, ). The mechanism of contrast agent-induced nephropathy has not been completely elucidated, but this result is attributed to a combination of renal ischemia, tubular epithelial cell toxicity, oxidative tissue damage, and apoptosis, effects that are very similar to those of AmB (, , , , ).In our study, we demonstrated that NAC reduced AmB-induced renal tubular apoptosis. Varlam et al. showed that rhIGF-1 decreases the incidence of renal tubular apoptosis (from 43% to 2%) in animals treated with AmB at 5 mg/kg/day and significantly reduces the frequency of apoptosis (from 52% to 18%) in animals receiving AmB at 10 mg/kg/day. In our study, AmB treatment resulted in a mean AI of 48.8% and the concomitant use of NAC decreased the AI to 23.5 to 27.4%. Nitescu et al. showed that treatment with 200 mg/kg NAC decreases the GFR and reduces plasma creatinine levels, hyperkalemia, and systemic oxidative stress in rats subjected to renal ischemic injury (). In another study, prophylactic NAC prevented decreases in the GFR associated with high doses of AmB (). Although we could show that NAC significantly reduced the AmB-induced tubular apoptosis, we did not evaluate the electrolytes in serum or urine samples or the serum creatinine levels because of technical unavailability. However, Varlam et al. demonstrated that rhIGF-1 improves the ability of the kidney to concentrate urine and prevents hypokalemia and dehydration.In summary, we demonstrated that renal tubular apoptosis caused by AmB could be reduced by the concomitant use of the antioxidant NAC. Our findings are promising for the clinical use of NAC for the reduction of AmB-induced nephrotoxicity. Further clinical studies are warranted.This project was supported by a grant from the Scientific and Technological Research Council of Turkey (TUBITAK).Published ahead of print on 4 May 2009.1. Appenroth, D., K. Winnefeld, H. Schroter, and M. Rost. 1993. Beneficial effect of acetylcysteine on cisplatin nephrotoxicity in rats. J. Appl. Toxicol. 13:189-192.
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[]Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)&Apoptosis of Keratinocytes and Psoriasis--《Chinese Journal of Dermatology》1997年04期
Apoptosis of Keratinocytes and Psoriasis
Xu Limin, Chen Xuerong, Yin Jinzhu. Department of Dermatology, The Third Teaching Hospital, Beijing Medical University, Beijing 100083
In order to study the status of cell apoptosis in psoriatic epidermis, we have investigated the changes of the lesions in various stages in patients with psoriasis vulgaris by using terminal deoxynueleotidyl transferase-mediation dUTP-biotin nick end labelling (TUNEL). The results showed that the highest frequency of apoptotic keratinocytes was observed in the early scaling papular lesions, and the frequency was reduced in the progressive maculo-papular lesions and the coalescent plaques successively. The frequency of hyperproliferation of epidermis was in the reverse order in comparison with the above results. These results suggest that increased apoptosis of keratinocytes is the initial change of psoriatic epidermis, then hyperproliferation of keratinoeytes follows.
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