Does repeated gold-nanoparticles administration affect pars distalis hormonal and folliculo-stellate cells in adult male albino rats?

INTRODUCTION: Worldwide, nanoparticles especially gold-nanoparticles (Au-NPs) are widely used in medicine, cancer treatment and cosmetic industry. They are easily conjugated with different biomedical and biological agents and effortlessly absorbed with few side effects. The pars distalis of the pituitary gland is considered as the maestro of the endocrine peripheral glands since it secrets trophic hormones that controls their functions. 5-10% of the non-granular pars distalis cells are folliculo-stellate cells (FSCs) that support the granular cells' functions. The aim of the study was to explore the histological and the biochemical effects of repeated exposure to Au-NPs on the pars distalis in adult male albino rats with highlighting the impact on FSCs. MATERIAL AND METHODS: Thirty-six adult male albino rats were divided equally into control group and Au-NPs group (received 40 µg/kg/day of 11 ± 2 nm spherical Au-NPs orally for 2 weeks). Then, rats were euthanized and deposition of Au-NPs in pars distalis was investigated. Biochemical investigations and histological studies including hematoxylin and eosin staining, periodic acid Schiff's reaction, immunohistochemistry (IHC) for S-100, connexin 43 (Cx43) and Cytochrome-C (Cyt-C) as well as electron-microscopic and morphometric studies were carried out. RESULTS: The Au-NPs group demonstrated structural disorganization in the pars distalis, inflammation, congestion and increased extracellular PAS-positive colloid deposition due to the accumulation of Au-NPs. A significant increase in the immunoreactivity of S-100, Cx43 and Cyt-c, along with a significant increase in TNF-a, MDA, and bFGF content in the pituitary homogenates, was noted as compared to the control group. Ultrastructurally, degenerative changes were observed in the secretory cells. FSCs showed proliferation and increased phagocytic activity. CONCLUSIONS: Repetitive exposure of adult male albino rats to Au-NPs prompted the accumulation of these nanoparticles in the pars distalis that was accompanied by cellular degeneration and dysfunction of the secretory cell and proliferation of FSCs. Thus, monitoring of the pars distalis hormonal levels might be useful for early detection of some hazardous effects possibly associated with the use of gold-nanoparticles.

The beneficial influence of rhubarb on 5-fluorouracil-induced ileal mucositis and the combined role of aquaporin-4, tumour necrosis factor-α, nuclear factor-kappa B & matrix metalloproteinase-9 in rat model: histological study.

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.

Contribution of angiotensin II in hepatic ischemia /reperfusion induced lung injury: Acute versus chronic usage of captopril.

BACKGROUND: Acute lung injury is one of the most popular consequences of hepatic ischemia/reperfusion (I/R) injury. Recently it was documented that renin-angiotensin system plays a key role in tissue inflammation, generation of reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNF-α) (the principal liver injury mediators) during I/R. MATERIAL AND METHODS: We investigated the effect of acute versus chronic usage of angiotensin converting enzyme inhibitor (captopril) on liver inflammation and lung injury caused by hepatic ischemia for 1h followed by 24h reperfusion. Forty adult Wistar male rats were divided into sham, I/R, I/R-acute captopril (100 mg/kg, 24 and 1.5 h before surgery) and I/R-chronic captopril (10 mg/kg/day for 28 days before surgery) groups. RESULTS: We found captopril pretreatment significantly decreased liver damage indices, adhesion molecules, and TNF-α level in hepatic and tracheal tissues. Histologically, acute captopril pretreatment significantly decreased hepatic Kupffer cells number and lung α-smooth muscle actin expression more than chronic pretreatment. Increased tracheal tone, in response to acetylcholine, was suppressed by acute and chronic captopril pretreatment. CONCLUSION: Angiotensin II plays a key role in tissue inflammation and airway hyperresponsiveness (AHR) via enhancing production of TNF-α. With more protection observed in lung, acute captopril could attenuate liver-induced lung injury via lowering TNF-α; a suggested possible mediator of airway hyperreactivity.

Effect of Stem Cells and Gene Transfected Stem Cells Therapy on the Pancreas of Experimentally Induced Type 1 Diabetes.

BACKGROUND AND OBJECTIVES: Insulin secretion entirely depends on Ca2＋ influx and sequestration into endoplasmic reticulum (ER) of ß-cells, performed by Sarco-ER Ca2＋-ATPase 2b (SERCA2b). In diabetes, SERCA2b is decreased in the ß-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 І (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.