Tamoxifen (TAM) is one of the most used drugs in the prevention and treatment of breast cancer. A set of common side effects was recorded associating its prolonged clinical use that ranges 3–10 years. This study aimed to investigate TAMinduced parietal cells (PCs) injury in rats and the possible protective effect of rhubarb (Rh) water extract (WE). Twentyfour adult female rats were distributed as: control group, TAM-group (3 mg/kg/day TAM for 4-weeks) and TAM+Rhgroup (combined 3 mg/kg/day TAM and 20 mg/kg Rh-WE for 4-weeks). Blood sample before euthanizing rats was tested for vitamin-B12. PCs in stomach fundus were examined using histological and transmission electron microscopic studies, besides immunohistochemistry for Caspase-3, proliferating cell nuclear antigen (PCNA) and hydrogen potassium (H + / K + )-ATPase. Gastric homogenates were inspected for malondialdehyde (MDA) by ELISA. TAM intake induced structural and ultrastructural alteration in rat PCs including ballooning degeneration, apoptosis, decreased canaliculi, increased tubulovesicular system and irregular-shaped mitochondria. A significant increase of Caspase-3 immunostaining and MDA expression in gastric tissue was associated with a significant decrease of PCNA and H + /K + -ATPase-immunostaining and in serum vitamin-B12 as compared to the control group. Combined oral intake of TAM and Rh-WE revealed a significant reversal of the previous findings. Conclusion: Prolonged use of oral TAM substantially affected the structure and function of gastric PCs which can be ameliorated by Rh-WE.

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.

Gastric ulcer is one of the most serious diseases. Nebivolol (Neb), a β1-blocker, exhibits vasodilator and antioxidative properties, simvastatin (Sim) antihyperlipidemic drug, exhibits anti-oxidative, anti-inflammatory properties and promote endogenous nitric oxide (NO) production. The aim of this study was to evaluate the gastroprotective effects of Neb and Sim against cold restraint stress (CRS)-induced gastric ulcer in rats. Rats were restrained, and maintained at 4°C for 3 hours. Animals were divided into six groups; control group, CRS group, and four treatment groups received ranitidine (Ran), Neb, Sim and both Neb and Sim. Treatments were given orally on a daily basis for 7 days prior to CRS. The gastroprotective effects of Neb and Sim were assessed biochemically by measuring variations in prostaglandins E2, NO, reduced glutathione and malondialdehyde, and functionally by estimating force of contractions of isolated rat fundus in the studied groups in response to acetylecholine stimulation and morphologically using hematoxylin and eosin staining, periodic acid Schiff ’s reaction and immunohistochemistry for cyclooxygenase 2 in gastric mucosa. CRS caused significant ulcerogenic effect. Alternatively, pretreatment with Ran, Neb, and Sim significantly corrected biochemical findings, pharmacological and histological studies.

BACKGROUND AND OBJECTIVES: Amiodarone (AM), a class 3 antiarrhythmic drug, has been associated with variety of adverse effects, the most serious of which is pulmonary toxicity. Ator (A) is a statin, known for their immunomodulatory and anti-inflammatory activities. Recent studies provide evidence of potential therapeutic effect of statins on lung injury. Adipose derived stem cells (ADSCs) have shown great promise in the repair of various tissues. The present study aimed at investigating and comparing the possible therapeutic effect of A and ADSCs on AM induced lung injury in albino rats. METHODS AND RESULTS: 34 adult male albino rats were divided into 5 groups: control group (Gp I), A group (Gp II) received 10 mg/kg of A orally 6 days (d)/week (w) for 4 weeks (ws), AM group (Gp III) received 30 mg/kg of AM orally 6 d/w for 4 ws, AM&A group (Gp IV) received AM for 4ws then A for other 4 ws and AM&SCs group (Gp V) received AM for 4 ws then injected with 0.5 ml ADSCs on 2 successive days intravenously (IV). Histological, histochemical, immunohistochemical and morphometric studies were performed. Group III displayed bronchiolitis obliterans, thickened interalveolar septa (IAS) and thickened vascular wall which were proven morphometrically. Increased area% of collagen fibers and apoptotic changes were recorded. All findings regressed on A administration and ADSCs therapy. CONCLUSION: Ator proved a definite ameliorating effect on the degenerative, inflammatory, apoptotic and fibrotic changes induced by AM. ADSCs administration denoted more remarkable therapeutic effect compared to A.
Adult ; Amiodarone* ; Animals ; Atorvastatin Calcium ; Bronchiolitis Obliterans ; Collagen ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Lung Injury* ; Lung* ; Male* ; Rats* ; Stem Cells*