The Effect of Thymoquinone, α7 Receptor Agonist and α7 Receptor Allosteric Modulator on the Cerebral Cortex in Experimentally Induced Alzheimer's Disease in Relation to MSCs Activation

BACKGROUND AND OBJECTIVES: Alzheimer’s disease (AD) is the most common form of dementia among older persons. Thymoquinone (TQ) has anti-inflammatory, anticonvulsant and antioxidant activity. A novel α7 nicotinic acetyl choline receptor (α7 nAChR ) agonist (PNU- 282987) have been identified to enhance the cognitive performance. An alternative treatment strategy via compounds known as nicotinic “positive allosteric modulators” (PAMs) has been reported. This study was designed to investigate the combination of PAM of α7 nAChRs with PNU- 282987 or with TQ as a possible treatment for AD in rat. METHODS: 48 male albino rats were divided into 4 groups. Group I (Control), Group II received lipopolysaccharide, 0.8 mg/kg by intraperitoneal injection (IPI) once, Group III received TQ 10 mg/kg by IPI, Group IV received PNU-120596 1 mg/kg by IPI, in addition to PNU-282987 1 mg/kg by IPI in subgroup IVa and TQ in subgroup b. All treatment drugs were given for 5 days. RESULTS: Acidophilic masses, deformed neurons, Congo red +ve masses and reduced Phospho-CREB immunoexpression were seen in group II. All changes regressed by treatment. Some CD44 +ve cells were noticed in group II and few +ve cells in subgroup IVa, that became multiple in group III and subgroup IVb. The histological, histochemical and immunohistochemical changes were confirmed statistically and significant differences were recorded. CONCLUSIONS: TQ or α7 nAChR agonist combined with PAM can have an important role in treatment of AD that is superior to thymoquinone alone. Exceptionally, TQ single or combined with PAM proved activation of MSC.

comparative study between the effects of dietary soya and estrogen replacement therapy on the lung of ovariectomized albino rats: histological and immunohistochemical study

Soy bean phytoestrogens have estrogenic properties and have been reported to be safe on female reproductive tissue. The present work aimed at comparing the effects of soya and estrogen in the lung of ovariectomized rats and demonstrating whether dietary soya could substitute estrogen replacement therapy. Thirty-nine adult female albino rats were divided into four groups. Group I [control] included nine rats. Group II included 10 rats ovariectomized for 6 months. Groups III and IV: each included 10 rats ovariectomized for 6 months and received estrogen replacement [group III] or soy bean [group IV]. Lung sections were subjected to H and E, Masson's trichrome stains, and immunohistomchemical staining of alpha smooth muscle actin [alpha SMA]. The mean smooth muscle thickness, area of collagen deposition, and area percent of alpha SMA were assessed. In group II, thick interalveolar septa with condensed collagen fibers, thickened bronchiolar smooth muscles, and cellular infiltration were detected. Positive alpha SMA immunoreactivity was noted in the thickened interalveolar septa. The mean smooth muscle thickness, collagen deposition, and area percent of alpha SMA immunoreactivity showed a significant increase in group II versus other groups, and there was significant decrease in groups III and IV versus group II. In groups III and IV, cellular infiltration and extravasated red blood cells were noted. Otherwise, they were comparable to the control group. It could be concluded that both soya and estrogen led to improved changes in the lung of ovariectomized rats almost to the same extent. Thus, soya might be recommended as a safe therapeutic substitute to estrogen, which has been reported to have side effects on female reproductive tissue

Thyroid gland dysfunction modulates ovarian response to estrogen and androgen receptors in albino rats

Hypothyroidism and hyperthyroidism are more common in women than in men, and it was reported that thyroid hormones play an essential role in ovarian physiology. This study aimed to simulate the clinical conditions of hypothyroidism and hyperthyroidism in adult female albino rats, and to detect the possible changes in ovarian estrogen and androgen hormone receptors associated with such clinical conditions. This study used 36 adult female albino rats. Rats were divided into three groups, with 1 2 rats each. Rats of the control group received 0.5 ml saline [0.9%] solution once daily. Six rats received the saline orally using a tube, and the other half received it by intraperitoneal injection for 4 weeks. The rats of the hypothyroid group received daily orally a dose of 18.75 mg/kg propylthiouracil dissolved in saline solution for 4 weeks, and the rats of the hyperthyroid group received a daily intraperitoneal dose of 40 microg/kg L-thyroxine dissolved in saline solution for 4 weeks. Vaginal smears were performed at the end of the experiment; only 22 rats coincided the diestrus phase of the cycle, sacrificed and sections were subjected to hematoxylin and eosin and immunohistochemical staining for estrogen and androgen receptors. In the hypothyroid group, few corpora lutea, atretic follicles, and dilated congested blood vessels were clearly seen. In the hyperthyroid group, the ovarian sections showed numerous corpora lutea; atretic follicles and markedly dilated congested blood vessels were also noted. A negative correlation was documented between estrogen receptor and androgen receptor immunoreactivity in the hypothyroid and hyperthyroid groups. This study suggested that thyroid hormones are important to maintain a normal estrous cycle and hence in the regulation of ovarian hormones. The mechanisms by which thyroid hormones influence ovarian function remain to be elucidated. However, it might be through their effect on the aromatase enzyme, which is the key regulator in ovarian hormones production reflected on the level of steroid hormones receptor expression