• Clinical and Experimental Reproductive Medicine
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• 제50권1호
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• pp.34-43
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• 2023

Objective: The aim of this study was to investigate the effect of royal jelly (RJ), a powerful natural antioxidant, on cyclophosphamide-induced ovarian damage. Methods: Thirty-two Wistar albino rats were divided into four groups. Oral treatment was administered to all rats for 16 days after a single intraperitoneal injection. The control group received intraperitoneal and oral saline; the RJ group received intraperitoneal saline and 100 mg/kg/day oral RJ; the cyclophosphamide group received intraperitoneal 100 mg/kg cyclophosphamide and oral saline; and the treatment group received intraperitoneal 100 mg/kg cyclophosphamide and 100 mg/kg/day oral RJ. The groups were compared in terms of ovarian reserve tests and histopathological changes in the ovary and uterus. Results: All follicle counts were higher in the treatment group than in the cyclophosphamide group. The increase in the number of preantral follicles (p=0.001) and the decrease in the number of atretic follicles (p=0.004) were statistically significant. RJ treatment significantly improved follicular degeneration and cortical fibrosis in the ovary and epithelial and gland degeneration in the uterus due to cyclophosphamide toxicity. Conclusion: According to these results, RJ reduces cyclophosphamide-related ovarian and endometrial damage in rats. For this reason, it should be further investigated to determine its effects on reproductive function.

• Toxicological Research
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• 제19권3호
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• pp.181-187
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• 2003

Effects of repeated treatment with butylated hydroxyanisole (BHA) on the induction of glutathione S-transferases (GSTs) and teratogenicity of cyclophosphamide were investigated in rats. Pregnant rats were orally treated with BHA (50 mg/kg) for 7 days, from days 6 to 12 of gestation, and intraperitoneally challenged with cyclophosphamide (15 mg/kg) 2 hr after the final treatment. On day 20 of gestation, the maternal and fetal abnormalities were examined. Separately, a part of rats was sacrificed for the assay of hepatic and placental GSTs activities on day 12 of gestation following 7-day treatment with BHA. Cyclophosphamide, administered on day 12 of gestation, induced 43.2% of fetal death and resorption, and 100% of malformations in live fetuses, in contrast to low fetal resorption (8.7%) and malformations (8%) in control group. The malformations include cranial defect and exencephaly (100%), micrognathia and tongue extrusion (100%), limb defects (40%), renal pelvic dilatation (39%), and cleft palate (15%). Interestingly, BHA induced GSTs activities by 62% and 46% over the control in liver and placenta, respectively, and remarkably reduced the fetal resorption (13.9%) and malformations, resulting in 62% of cranial defect and exencephaly, 68% of micrognathia and tongue extrusion, 29% of limb defects, and 14% of renal pelvic dilatation. Taken together, it is suggested that a long-term pretreatment with BHA could substantially prevent fetuses from abortion and malformations following intrauterine exposure to teratogens including cyclophosphamide by inducing phase II antioxidant enzymes such as GSTs.

• 한국식품과학회지
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• 제35권6호
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• pp.1204-1208
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• 2003

항암제인 cyclophosphamide를 흰쥐에 투여하여 유발된 빈혈증상에 대하여 한국당귀, 중국당귀, 일당귀의 투여가 빈혈회복에 미치는 효능을 비교한 연구로서, Sprague-Dawley계 수컷 흰쥐에게 cyclophosphamide를 30mg/kg BW/day로 3회 복강 투여 후, 참당귀, 중국당귀와 일당귀 추출물을 1 g/kg BW/day로 14일 동안 경구 투여하였다. Cyclophosphamide 투여로 체중감소는 대표적인 전신증상으로 나타났으나 당귀추출물의 투여가 cyclophosphamide에 의한 체중감소 부작용을 저해함으로써 체중증가를 유도한 것으로 볼 수 있다. 참당귀 투여군은 적혈구 용적(hematocrit, Hct) 변화, 적,백혈구수 변화, 혈색소 농도 변화, 혈청 iron, transferrin 포화도 등의 항목에 대하여 유의성 있는 회복 효과를 나타내었고, 중국 및 일당귀 투여군은 백혈구수 감소에 대하여 유의성 있는 회복효과를 나타내었다. Cyclophosphamide 투여 후 비타민 $B_{12}$ 농도는 정상군에 비해 유의적으로 낮았고, 중국당귀, 참당귀, 일당귀 순으로 비타민 $B_{12}$ 농도가 유의적으로 증가하는 것을 관찰하였다. 이는 당귀가 비타민 $B_{12}$의 농도를 증가시키면서 혈액생산작용에 도움을 줄 것으로 여겨진다. 결론적으로 참당귀추출물 투여로 인해 혈액수치가 향상된 결과는 암 환자가 화학요법으로 인하여 생긴 빈혈치료에 도움이 될 것이라 생각된다.

• Journal of Chest Surgery
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• 제22권6호
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• pp.914-920
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• 1989

Bleomycin and cyclophosphamide are widely used and effective anti-cancer agents for treatment of various forms of cancer. Bleomycin has no myelotoxicity, but because of potential risk of pulmonary complications including interstitial pneumonitis and idiopathic interstitial pulmonary fibrosis, it has been limited in use. Some investigator has also suggested that cyclophosphamide can induce pulmonary toxicity like bleomycin. Recently, The combination chemotherapy including bleomycin and cyclophosphamide has been adopted effectively in some types of cancer. But there are no available literatures for synergistic effect of pulmonary toxicity in combination chemotherapy including these two drugs. We tried this study to observe synergism of pulmonary toxicity using these two drugs in rats. The animals were divided into five groups: group 1 received intra-peritoneal injection of saline, group 2-a received only bleomycin 0.1 mg [0.4 mg/kg] by intra-peritoneal injection twice a week, group 2-b received only bleomycin 0.5 mg [2 mg/kg] by intra-peritoneal injection twice a week, group 3-a received bleomycin 0.1 mg [0.4 mg/kg] twice a week +cyclophosphamide 5 mg [20 mg/kg] two weeks interval by intra-peritoneal injection, group 3-b received bleomycin 0.5 mg [2 mg/kg] twice a week + cyclophosphamide 5 mg[20 mg/kg] two weeks interval by intra-peritoneal injection. The animals were sacrificed at 2 and 4 weeks later. Lung tissues were obtained and observed by light microscope. The results are as follows: 1. The pathologic findings of group 1 were normal without change. 2. There was no difference between group 2-a and group 3-a at 2 weeks later, group 3-a, however, revealed more severe change in lung tissue at 4 weeks later compared with group 2-a. 3. In group 3-b there was more severe pulmonary injury compared with group 2-b at 2 and 4 weeks later. We conclude that the combined administration of bleomycin and cyclophosphamide induce more severe pulmonary toxic effect than bleomycin administration alone and the combination chemotherapy including these two drugs will be require special attention to selection of the dose of each drug.

• 동국한의학연구소논문집
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• 제2권1호
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• pp.167-176
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• 1993

The purpose of this study is to invesigate the effect of Yook-Gun-ja-Tang on the side effect of cyclophosphamide to splenical tissue in the rat. The experimental animal were divided into normal group, control group, sample group by way of method treatment of the drug. Each group was sacrificed and stained in accordance with the schedule and observed under light microscope. The results of this study were as follow : 1. After treatment of Yook-Gun-Ja-Tang, rat's weight and volume were more increased than normal group and control group. 2. The decrease of the numbers of the splenical tissue after administration of cyclophosphamide were recovered with prescription of the Yook-Gun-la-Tang ; The decreases of white pulp, red pulp, marginal zone, central artery were recovered. 3. Increased macrophages in red pulp of splenical tissue of rats with administration of cyclophosphamide were decreased after treatment of Yook-Gun-Ja-Tang. These results appeared to suggest that Yook-Gun-Ja-Tang might be effective on the: side effect of cyclophosphamide to splenical tissue of rat's and applied to the prescription for the recovery of the side effect of drug.

• 동의생리병리학회지
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• 제19권2호
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• pp.429-433
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• 2005

We investigated the effects of aqueous extract from talc for suppression in the process of cyclophosphamide-induced cystitis in the rat. The weight of urinary bladder was increased in the cyclophosphamide-injected rat compared with normal, but the increase of weight was arrested by intake of talc. More similar results showed in the uric test involving nitrate content and blood cell number and serum analysis involving the content of blood urea nitrogen and uric acid in the talc challenged rat compared with control one. More severe histological changes of urinary bladder such as edema, wall thickness, bleeding, vacuolation in mucosal epithelium were demonstrated in the rat injected with cyclophosphamide compared with normal. Fewer scores of these changes such as edema and bleeding were observed in rats treated with talc. In the immunohistochemical analysis, the expression of inflammatory-related protein examined tended to increase in the urinary bladder of cyclophosphamide-injected rat, especially COX-2 and $TNF-{\alpha}$ in mucosal epithelium and iNOS and $IL-1{\beta}$ in mucosal and muscular layer. The decline of these immunoreation were observed in the talc treated rat, significant decrease of COX-2 was detected in mucosal epithelium and iNOS in submucosal layer. These results suggest that talc may use as a useful therapeutic agent for noninfectious cystitis.

• Tuberculosis and Respiratory Diseases
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• 제55권2호
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• pp.175-187
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• 2003

연구배경 : 특발성 간질성 폐렴의 치료제로 스테로이드가 많이 사용되고 있으나 병리 소견에 따라 치료효과가 다르고 부작용이 많아 Cyclophosphamide와 같은 세포독성 약물들이 추천되고 있다. 그러나 그 효과 및 우월성에 대해선 아직도 논란이 많다. 이에 각 약제의 치료효과 및 부작용에 대해 알아보고자 본 연구를 시행하였다. 방 법 : 1996년 7월부터 2002년 6월까지 삼성서울병원에서 수술적 폐생검을 통해 확진된 특발성 간질성 폐렴환자 87명(UIP 61명, NSIP 26명)을 대상으로 치료약제, 치료반응 및 약물 부작용에 대해 후향적 조사를 시행하였다. 치료반응은 최소 6개월 이상의 연속적인 약제 투여와 약제 투여 후 1년 이상의 추적 관찰이 이루어진 환자 55례(UIP 32례, NSIP 23례)을 대상으로 치료 후 6개월, 12개월에 임상 증세, 폐기능 검사, 방사선학적 소견의 3가지를 기준으로 호전, 안정, 악화(사망 포함)로 판정하였다. 약물 부작용은 최소 한 종류 이상의 약제 투여가 이루어진 환자 91례(스테로이드 단독 요법 42례, CP 병합 요법 49례)를 대상으로 조사하였다. 결 과 : 1) NSIP 환자가 UIP 환자보다 약제 종류에 상관없이 호전 반응이 많았다(6개월 : 78.3% vs. 9.4%, p<0.001, 12개월 : 69.6% vs. 9.4%, p<0.001). 2) UIP 환자에서 약제에 따른 치료반응의 차이는 없었다(p>0.05) 3) NSIP 환자에서 약제에 따른 치료반응의 차이는 없었다(p>0.05) 4) 약물 부작용으로 투여가 중단된 경우는 스테로이드 치료군에서는 감염, 불안 장애 등이, cyclophosphamide 치료군에서는 위장 장애, 출혈성 감염 등이 있었고, 스테로이드 치료 군(15례, 35.7%)에서 cyclophosphamide 치료군(7례, 14.3%)보다 많았다(p=0.017). 결론 : 스테로이드 보다 부작용이 적고 동등한 치료효과를 보이는 cyclophosphamide는 특발성 UIP보다 치료반응이 좋은 특발성 NSIP에서 보다 적극적으로 이용될 수 있다고 사료된다.

• 치과방사선
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• 제21권2호
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• pp.203-220
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• 1991

The purpose of this study was to investigate the changes of morphology and structure of bone tissue, caused by administration of high-dose hydrocortisone, elcatonin and cyclophosphamide. In order to carry out experiment, 60 four-week old Sprague-Dawley strain rats weighing about 107 gms were selected and divided into experimental group and control group. The experimental group was subdivided into three groups, assigned fifteen rats for each group, by the different drugs administered. Each experimental group was then categorized as follows: hydrocortisone 30㎎/㎏ b.w. with daily subcutaneous injection, elcatonin 20U/㎏ b.w. with daily subcutaneous injection, and cyclophosphamide 100㎎/㎏ b.w. with a single intraperitoneal injection. Fifteen rats were injected daily with 5㎖/㎏ b.w. of normal saline solution subcutaneously in control group. Rats in control group and experimental group were serially sacrificed on the 6th, the 15th and the 22nd day after injection of normal saline, hydrocortisone, elcatonin and cyclophosphamide, respectively. Being sacrificed, both sides of mandibular condyles were removed and fixed with 10% neutral formaline. The one side of mandibular condyles was radiographed with soft X-ray apparatus. Thereafter, the obtained radiographs were observed, and the bone density of condylar head and condylar neck regions was measured by use of transferring video-based digital radiograph. The other side was further decalcified and embedded in paraffin as usual manner, then sectioned and stained with hematoxylin and eosin, observed by light microscope. The obtained results were as follows: 1. Sclerotic changes with regularly increased trabecular pattern were seen throughout experimental periods in hydrocortisone group. Increased the number of trabecular pattern with irregularity and periodic striation on the periphery of condylar head region were appeared with lapse of time in elcatonin group. In cyclophosphamide group, irregular trabecular pattern and stippled radiopacities on mandibular condyle were observed with lapse of time. 2. The bone density of condylar head region was increased in hydrocortisone group, decreased in elcatonin group, and tended to be decreased in cyclophosphamide group, compared with that of control group according to the experimental periods. 3. The bone density of condylar neck region tended to be rather increased in hydrocortisone group, elcatonin group and cyclophosphamide group, depending on the experimental periods. 4. In microscopic studies, there were irregular trabecular bonds and osteoblastic activity in hydrocortisone group and elcatonin group throughout experimental periods, degenerative cartilage and trabecular bones in the 6th day and densely calcified trabecular bones in the 22nd day in cyclophosphamide group.

• 대한한방내과학회지
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• 제23권1호
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• pp.123-131
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• 2002

Objective : It is well known that modern chemotherapy against cancer has side effects to a living body, especially hemopoietic and immunologial disfunctions. However, there are no effective ways to reduce them. Recently, traditional Korean herb medicine has been reported to have some biological modifying responses. Therefore, we hypothesized that additional application of herb medicine during chemotherapy is more effective to reduce its side effects. While we were studying the effects, we have observed the inhibitory effect of Soamgudamikgitang on formation of side effects derived from Cyclophosphamide, it has been used in clinical practice at Kyung Hee Medical Center. Methods : We injected 200mg/kg of Cyclophosphamide, one time, to an experimental group, consisting of ten mice. We divided them into eight groups: normal, CPX, SAKT 2mg, SAKT 10mg, SAKT 50mg, SAKT 2mg, CPX, SAKT 10mg+CPX, SAKT 50mg+CPX. We injected Soamgudamikgitang seven days, five days, three days, and one day before we injected CPX. One day, three days, and five days after CPX injection, we injected Soamgudamikgitang again and then killed all the mice. The parameters determined in this experiment were daily body weight liver and spleen weight, RBC, WBC, and platelet for hemopoietic dysfunction and AST, ALT for hepatotoxicity, BUN, creatine for renal toxcity, lymphocyte proliferation activity and lymphocyte subsets for immunological toxcity. Results : We have found that Soamgudamikgitang has inhibitory effects on the formation of Cyclophosphamide's side effects. Significant differences between the group, which contained Cyclophosphamide, and the other group, which contains Cyclophosphamide and 2, 10, 50mg of Soamgudamikgitang respectively were observed. Platelets(2mg of Soamgudamikgitang, p<0.05 ;10mg, p<0.01 ;50mg, p<0.001), liver weight(50mg, p<0.01), spleen weight(10mg, p<0.05), AST(all groups, p<0.01), ALT(2mg, p<0.01 ;10mg, p<0.05 ;50mg, p<0.01), BUN(2mg, p<0.01 ;50mg, p<0.05). Although immunological in both lymphocyte proliferation and its subsets were not observed, which shows that Soamgudamikgitang has a strong effect on T cell activities. Conclusions : From the above results, we can expect that the combined therapy of Soamgudamikgitang and Cyclophosphamide is more effective for treating cancer patients.

• Tuberculosis and Respiratory Diseases
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• 제45권2호
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• pp.429-436
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• 1998

저지들은 이전의 문헌과 비슷하게 만성 특발성 혈소판 감소증 환자에서 cyclophosphamide와 스테로이드 치료도중 cyclo-phosphamide 최초 투여 시작일로부터 1~2개월이내에 발생한 조기 발현형 폐독성으로 개흉폐생검을 통하여 진단한 후 조기에 cyclophosphamide의 투여 중단과 함께 스테로이드 사용에도 불구하고 진행성 호흡부전으로 사망한 환자를 경험하였기에 이틀 문헌고찰과 함께 보고하는 바이다.