ABSTRACT
A 5-fluorouracil (5-FU) is used for cancer treatment despite its cytotoxic sequelae on healthy cells, especially the rapid proliferating ones. Intestinal mucositis is one of the most frequent chemotherapeutic debilitating sequelae. Rhubarb (Rh), an ancient herb, is known for its curing effect on gastrointestinal complications. This study aims to detect the role of aquaporin-4 (AQP-4), tumour necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB), and matrix metalloproteinase-9 (MMP-9) in 5-FU-induced ileal histological and biochemical changes and the potential therapeutic effect of Rh water extract on these changes in rats. A 45 rats were divided into 3 groups; control, 5-FU (single intraperitoneal injection of 150 mg/kg/rat) and Rh-treated (oral 20 mg/kg/day/rat for 8 days). The change in animals’ weight, incidence of diarrhoea and AQP-4 and TNF-α values in ileal homogenates were measured. Ileal sections were subjected to hematoxylin and eosin stain, periodic acid Schiff (PAS)-reaction and MMP-9, NF-κB and AQP-4 immunohistochemical staining. A 5-FU group revealed marked ileal mucosal damage associated with a significant decrease in the mean body weight, AQP-4 level and area percent of PAS and AQP-4 positive reaction. Significant increase in the mean incidence of diarrhoea, TNF-α value and area percent of MMP-9 and NF-κB was detected. These changes were significantly corrected with Rh administration. A 5-FU resulted in severe ileal mucositis through TNF-α, NF-κB, MMP-9, and AQP-4 disturbances. Rh treatment was highly effective in preventing such mucositis.
ABSTRACT
BACKGROUND AND OBJECTIVES: Insulin secretion entirely depends on Ca²⁺ influx and sequestration into endoplasmic reticulum (ER) of β-cells, performed by Sarco-ER Ca²⁺-ATPase 2b (SERCA2b). In diabetes, SERCA2b is decreased in the β-cells leading to impaired intracellular Ca²⁺ homeostasis and insulin secretion. Adipose mesenchymal stem cells (AMSCs) play a potential role in transplantation in animal models. The present study aimed at investigating and comparing the therapeutic effect of non-transfected AMSCs and SERCA2b gene transfected AMSCs on the pancreas of induced diabetes type 1 in rat. METHODS AND RESULTS: 58 adult male albino rats were divided into: Donor group: 22 rats, 2 for isolation, propagation and characterization of AMSCs and SERCA2b transfected AMSCs, in addition 20 for isolated islet calcium level assessment. Group I (Control Group): 6 rats, Group II (Diabetic Group): 10 rats, 50 mg streptozotocin (STZ) were injected intraperitoneal (IP), Group III (AMSCs Group): 10 rats, 1×10⁶ AMSCs were injected intravenous and Group IV (SERCA2b transfected AMSCs Group): 10 rats, 1×10⁶SERCA2b transfected AMSCs were injected as in group III. Groups I, II, III and IV were sacrified 3 weeks following confirmation of diabetes. Serological, histological, morphometric studies and quantitative polymerase chain reaction (qPCR) were performed. Nuclear, cytoplasmic degenerative and extensive fibrotic changes were detected in the islets of group II that regressed in groups III and IV. Isolated islet calcium, blood glucose, plasma insulin and qPCR were confirmative. CONCLUSIONS: AMSCs and SERCA2b gene transfected AMSCs therapy proved definite therapeutic effect, more obvious in response to SERCA2b gene transfected AMSCs.