Merwid-Ląd Anna, Ksiądzyna Dorota, Hałoń Agnieszka, Chlebda-Sieragowska Ewa, Trocha Małgorzata, Szandruk Marta, Sozański Tomasz, Magdalan Jan, Kopacz Maria, Kuźniar Anna, Nowak Dorota, Pieśniewska Małgorzata, Szeląg Adam
Department of Pharmacology, Wroclaw Medical University, Wrocław, Poland.
Department of Pharmacology, Wroclaw Medical University, Wrocław, Poland.
Pharmacol Rep. 2015 Dec;67(6):1259-63. doi: 10.1016/j.pharep.2015.05.020. Epub 2015 Jun 4.
The aim of this study was to evaluate the effect of morin-5'-sulfonic acid sodium salt (NaMSA) on cyclophosphamide-induced gastrointestinal changes in rats.
Rats received intragastrically 0.9% saline (group C), cyclophosphamide (15 mg/kg) (group CX), NaMSA (100 mg/kg) (group M) or cyclophosphamide (15 mg/kg) with NaMSA (100 mg/kg) (group M-CX), respectively, for 10 days.
No histological lesions were observed in the liver and the large intestine in the control group and group receiving NaMSA. In the cyclophosphamide-treated group, a generalized blurred trabecular structure, hepatocyte apoptosis, focal and diffuse necrosis were noticed in the liver and atypia of epithelial cells or adenoma were noticed in the large intestine. In the group receiving both cyclophosphamide and NaMSA, hepatocyte apoptosis in the liver was observed less frequently. Histological examination of the small intestine revealed: low-grade dysplasia adenoma in the C, M, CX and M-CX group (in 44%, 0%, 100%, and 55.6% of specimens, respectively) with adenocarcinoma in 55.6% of specimens in the cyclophosphamide-receiving group only. Adenoma with high-grade dysplasia was observed in the control and NaMSA-receiving group with a similar frequency (22%). In addition to the histological evaluation, blood cell count parameters, as well as total protein concentration, blood glucose level, amylase, ALT, AST and GGTP activities were evaluated. Cyclophosphamide impaired weight gain, decreased blood cell count parameters and total protein concentration, and increased the GGTP activity. Those changes were not reversed by NaMSA.
Summing up, NaMSA may protect against some cyclophosphamide-induced histological abnormalities in the gastrointestinal tract, including intestinal neoplasia in rats.
本研究旨在评估桑色素 - 5'- 磺酸钠盐(NaMSA)对环磷酰胺诱导的大鼠胃肠道变化的影响。
大鼠分别经胃内给予0.9%生理盐水(C组)、环磷酰胺(15 mg/kg)(CX组)、NaMSA(100 mg/kg)(M组)或环磷酰胺(15 mg/kg)与NaMSA(100 mg/kg)(M - CX组),持续10天。
对照组和接受NaMSA的组中,肝脏和大肠未观察到组织学病变。在环磷酰胺治疗组中,肝脏出现普遍模糊的小梁结构、肝细胞凋亡、局灶性和弥漫性坏死,大肠出现上皮细胞异型增生或腺瘤。在同时接受环磷酰胺和NaMSA的组中,肝脏中肝细胞凋亡的发生率较低。小肠组织学检查显示:C组、M组、CX组和M - CX组均有低级别发育异常腺瘤(分别占标本的44%、0%、100%和55.6%),仅接受环磷酰胺的组中有55.6%的标本出现腺癌。对照组和接受NaMSA的组中高级别发育异常腺瘤的发生率相似(22%)。除了组织学评估外,还评估了血细胞计数参数以及总蛋白浓度、血糖水平、淀粉酶、ALT、AST和GGTP活性。环磷酰胺损害体重增加,降低血细胞计数参数和总蛋白浓度,并增加GGTP活性。NaMSA并未逆转这些变化。
综上所述,NaMSA可能预防环磷酰胺诱导的大鼠胃肠道某些组织学异常,包括肠道肿瘤形成。