Abstract：
OBJECTIVE: In the present study, the protective effects of adenosine triphosphate (ATP), Benidipine, and Lacidipine on potential kidney damage induced by 5-fluorouracil (5-FU) were investigated in rats.
METHODS: Totally 48 rats were divided into 8 groups: healthy (HG), 5-FU (FUG), ATP+5-FU (AFU), Benidipine+5-FU (BFU), Lacidipine+5-FU (LFU), ATP+Benidipine+5-FU (ABFU), ATP+Lacidipine+5-FU (ALFU) and Benidipine+Lacidipine+5-FU (BLFU). In a 10-day period, ATP (4 mg/kg) was administered intraperitoneally, and Benidipine (4 mg/kg) and Lacidipine (4 mg/kg) were administered orally once a day. On days 1, 3, and 5, 5-FU (100 mg/kg) was administered intraperitoneally one hour after the drug was administered. Afterward, the rats were euthanized, and kidney tissues were removed. An analysis of malondialdehyde, total glutathione, superoxide dismutase, and catalase was performed on tissues, as well as a histopathological examination. A creatinine and blood urea nitrogen analysis were performed on blood samples.
RESULTS: It was revealed that 5-FU decreased the amount of total glutathione, superoxide dismutase, and catalase activities in rat kidney tissues and increased malondialdehyde. Further, increased serum creatinine and blood urea nitrogen levels, as well as histopathological examination of kidney tissues, were found in the 5-FU group. ATP+Benidipine and ATP treatments were the most effective in preventing both biochemical and histopathological changes induced by 5-FU. A treatment with Benidipine improved biochemical and histopathologic data, but not to the same extent as a treatment with ATP+Benidipine and ATP. As a result of Lacidipine+ATP combination, 5-FU-induced biochemical changes in kidney tissue were partially inhibited, but the degree of histopathologic damage remained unchanged. Neither Benidipine+Lacidipine nor Lacidipine showed a protective effect on both biochemical changes and histopathologic damage.
CONCLUSIONS: It may be possible to prevent nephrotoxicity by adding ATP + Benidipine or ATP to 5-FU treatment.
METHODS: Totally 48 rats were divided into 8 groups: healthy (HG), 5-FU (FUG), ATP+5-FU (AFU), Benidipine+5-FU (BFU), Lacidipine+5-FU (LFU), ATP+Benidipine+5-FU (ABFU), ATP+Lacidipine+5-FU (ALFU) and Benidipine+Lacidipine+5-FU (BLFU). In a 10-day period, ATP (4 mg/kg) was administered intraperitoneally, and Benidipine (4 mg/kg) and Lacidipine (4 mg/kg) were administered orally once a day. On days 1, 3, and 5, 5-FU (100 mg/kg) was administered intraperitoneally one hour after the drug was administered. Afterward, the rats were euthanized, and kidney tissues were removed. An analysis of malondialdehyde, total glutathione, superoxide dismutase, and catalase was performed on tissues, as well as a histopathological examination. A creatinine and blood urea nitrogen analysis were performed on blood samples.
RESULTS: It was revealed that 5-FU decreased the amount of total glutathione, superoxide dismutase, and catalase activities in rat kidney tissues and increased malondialdehyde. Further, increased serum creatinine and blood urea nitrogen levels, as well as histopathological examination of kidney tissues, were found in the 5-FU group. ATP+Benidipine and ATP treatments were the most effective in preventing both biochemical and histopathological changes induced by 5-FU. A treatment with Benidipine improved biochemical and histopathologic data, but not to the same extent as a treatment with ATP+Benidipine and ATP. As a result of Lacidipine+ATP combination, 5-FU-induced biochemical changes in kidney tissue were partially inhibited, but the degree of histopathologic damage remained unchanged. Neither Benidipine+Lacidipine nor Lacidipine showed a protective effect on both biochemical changes and histopathologic damage.
CONCLUSIONS: It may be possible to prevent nephrotoxicity by adding ATP + Benidipine or ATP to 5-FU treatment.
摘要：
目的：在本研究中，三磷酸腺苷（ATP）的保护作用，贝尼地平,在大鼠中研究了拉西地平对5-氟尿嘧啶（5-FU）引起的潜在肾脏损害的影响。
方法:将48只大鼠随机分为8组:5-FU(FUG),ATP+5-FU(AFU),贝尼地平+5-FU(BFU),拉西地平+5-FU(LFU),ATP+贝尼地平+5-FU（ABFU），ATP+拉西地平+5-FU(ALFU)和贝尼地平+拉西地平+5-FU(BLFU)。在10天的时间里，腹膜内给予ATP(4mg/kg),和贝尼地平(4mg/kg)和拉西地平(4mg/kg)每天一次口服给药。在第1、3和5天,在给药1小时后腹膜内施用5-FU(100mg/kg)。之后,老鼠被安乐死，肾脏组织被切除。丙二醛的分析，总谷胱甘肽，超氧化物歧化酶,过氧化氢酶在组织上进行，以及组织病理学检查。对血液样品进行肌酐和血尿素氮分析。
结果：发现5-FU降低了总谷胱甘肽的含量，超氧化物歧化酶,和大鼠肾脏组织中的过氧化氢酶活性和丙二醛增加。Further,血清肌酐和血尿素氮水平升高，以及肾组织的组织病理学检查，在5-FU组中发现。ATP贝尼地平和ATP治疗在预防5-FU诱导的生化和组织病理学变化方面最有效。贝尼地平治疗改善了生化和组织病理学数据，但与用ATP+贝尼地平和ATP治疗的程度不同。作为拉西地平+ATP组合的结果，5-FU诱导的肾组织生化改变被部分抑制,但组织病理学损伤程度保持不变。贝尼地平拉西地平和拉西地平均未显示出对生化变化和组织病理学损伤的保护作用。
结论：可能通过在5-FU治疗中加入ATP+贝尼地平或ATP来预防肾毒性。
方法:将48只大鼠随机分为8组:5-FU(FUG),ATP+5-FU(AFU),贝尼地平+5-FU(BFU),拉西地平+5-FU(LFU),ATP+贝尼地平+5-FU（ABFU），ATP+拉西地平+5-FU(ALFU)和贝尼地平+拉西地平+5-FU(BLFU)。在10天的时间里，腹膜内给予ATP(4mg/kg),和贝尼地平(4mg/kg)和拉西地平(4mg/kg)每天一次口服给药。在第1、3和5天,在给药1小时后腹膜内施用5-FU(100mg/kg)。之后,老鼠被安乐死，肾脏组织被切除。丙二醛的分析，总谷胱甘肽，超氧化物歧化酶,过氧化氢酶在组织上进行，以及组织病理学检查。对血液样品进行肌酐和血尿素氮分析。
结果：发现5-FU降低了总谷胱甘肽的含量，超氧化物歧化酶,和大鼠肾脏组织中的过氧化氢酶活性和丙二醛增加。Further,血清肌酐和血尿素氮水平升高，以及肾组织的组织病理学检查，在5-FU组中发现。ATP贝尼地平和ATP治疗在预防5-FU诱导的生化和组织病理学变化方面最有效。贝尼地平治疗改善了生化和组织病理学数据，但与用ATP+贝尼地平和ATP治疗的程度不同。作为拉西地平+ATP组合的结果，5-FU诱导的肾组织生化改变被部分抑制,但组织病理学损伤程度保持不变。贝尼地平拉西地平和拉西地平均未显示出对生化变化和组织病理学损伤的保护作用。
结论：可能通过在5-FU治疗中加入ATP+贝尼地平或ATP来预防肾毒性。
