Cheraghi Hadi, Khaki Zohreh, Malekinejad Hassan, Sasani Farhang
Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran;
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran;; Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran;
Vet Res Forum. 2015 Fall;6(4):319-26. Epub 2015 Dec 15.
Mycophenolate mofetil (MMF) is a selective inhibitor of Inosine-5'-monophosphate dehydrogenase. Gastrointestinal (GI) disturbances in immature ones are reported for MMF-induced compilations, which in the case of occurrence dose reduction is required. Thus, in the present study, the fructooligosaccharide raftilose(®) (RFT) was co-administrated with MMF to estimate the protective effect of RFT against MMF-induced GI complications. Thirty six immature male Wistar rats were divided into six groups including: Control (normal saline), RFT-treated (100 mg kg(-1)), MMF-treated (20 mg kg(-1)), MMF + LRFT (50 mg kg(-1)), MMF + MRFT (100 mg kg(-1)) and MMF + HRFT (200 mg kg(-1)) groups. The hematocrit (Hct), lymphocyte/total WBC, feces water content and pH were analyzed. Moreover, the hepatic functional tests, kidney-related biomarkers, lipid and protein profiles, total antioxidant capacity (TAC), malondialdehyde (MDA) and nitric oxide (NO) contents were assessed. Co-administration of RFT stabilized the MMF-reduced body weight. The MMF significantly diminished Hct and lymph/total WBC (p < 0.05). Only MRFT enhanced the lymphocyte/total WBC. Increased water content, no changes in feces pH, increased serum ALT and AST, no alteration in urea and mild enhancement in creatinine were demonstrated in MMF-received animals. However, RFT at low dose ameliorated the feces parameters and reduced ALT. No significant changes were demonstrated for serum lipid and protein profiles in MMF- and RFT + MMF-treated groups. The RFT enhanced the serum TAC, reduced MDA and NO contents. In conclusion, our data suggested that RFT could be considered as an effective agent to subsidize the MMF-induced clinical, hematological and biochemical disorders.
霉酚酸酯(MMF)是肌苷-5'-单磷酸脱氢酶的选择性抑制剂。据报道,未成熟个体中MMF诱导的并发症会出现胃肠道(GI)紊乱,一旦发生这种情况,需要减少剂量。因此,在本研究中,将低聚果糖水苏糖(®)(RFT)与MMF联合给药,以评估RFT对MMF诱导的胃肠道并发症的保护作用。将36只未成熟雄性Wistar大鼠分为六组,包括:对照组(生理盐水)、RFT治疗组(100 mg kg⁻¹)、MMF治疗组(20 mg kg⁻¹)、MMF + LRFT组(50 mg kg⁻¹)、MMF + MRFT组(100 mg kg⁻¹)和MMF + HRFT组(200 mg kg⁻¹)。分析了血细胞比容(Hct)、淋巴细胞/总白细胞、粪便含水量和pH值。此外,还评估了肝功能测试、肾脏相关生物标志物、脂质和蛋白质谱、总抗氧化能力(TAC)、丙二醛(MDA)和一氧化氮(NO)含量。RFT与MMF联合给药可稳定MMF降低的体重。MMF显著降低了Hct和淋巴细胞/总白细胞(p < 0.05)。只有MRFT提高了淋巴细胞/总白细胞。接受MMF的动物粪便含水量增加、粪便pH值无变化、血清谷丙转氨酶(ALT)和谷草转氨酶(AST)升高、尿素无变化以及肌酐轻度升高。然而,低剂量的RFT改善了粪便参数并降低了ALT。MMF组和RFT + MMF治疗组的血清脂质和蛋白质谱无显著变化。RFT提高了血清TAC,降低了MDA和NO含量。总之,我们的数据表明,RFT可被视为一种有效药物,用于缓解MMF诱导的临床、血液学和生化紊乱。