Comparative analysis of oral and local intraovarian administration of metformin and nanoparticles (NPs11) in alleviating testosterone-induced polycystic ovary syndrome in rats.

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic dysfunction. This study aims to compare the oral and local treatments of metformin or its nanoparticles (NPs11) for ameliorating PCOS in rats. Rats were divided into 4 groups: the control group with no drug treatment; the PCOS group, where subcutaneous testosterone was given (10 mg/kg/day) for 28 days; the MET group, where metformin was administered orally or locally; and the NP group, where metformin NPs11 were also administered orally or locally. Oral administrations were for 21 days, while local injection was performed once surgically. After 7 weeks, all rats were sacrificed; blood glucose and serum hormonal levels and lipid profile were estimated, and the ovaries were assessed by histopathological, Ki-67 immunohistochemical, and histomorphometric evaluations. Blood glucose levels were significantly decreased in groups of orally administered metformin or NPs11 only, while the most efficient option for modulating PCOS-induced hormonal and lipid profile changes was intraovarian injection of NPs11. The ovaries of PCOS rats demonstrated large follicular cysts, massive collagen depositions, and attenuated Ki-67 immunoexpression. Also, the PCOS group revealed a significant decrease in the count of all stages of growing follicles, corpora lutea, granulosa cell layer thickness, and surface area of corpora lutea, in addition to an increase in the number of atretic follicles and follicular cysts, theca cell layer thickness, and surface area of the follicular cysts. All these parameters were recovered with metformin or their NPs11 treatments in different degrees, while local injection of NPs11 was the best option.

Experimental study of the effects of nitroglycerin, botulinum toxin A, and clopidogrel on bipedicled superficial inferior epigastric artery flap survival.

Beneficial effects could be achieved by various agents such as nitroglycerin, botulinum toxin A (BoTA), and clopidogrel to improve skin flap ischaemia and venous congestion injuries. Eighty rats were subjected to either arterial ischaemia or venous congestion and applied to a bipedicled U-shaped superficial inferior epigastric artery (SIEA) flap with the administration of nitroglycerin, BoTA, or clopidogrel treatments. After 7 days, all rats were sacrificed for flap evaluation. Necrotic area percentage was significantly minimized in flaps treated with clopidogrel (24.49%) versus the ischemic flaps (34.78%); while nitroglycerin (19.22%) versus flaps with venous congestion (43.26%). With ischemia, light and electron microscopic assessments revealed that nitroglycerin produced degeneration of keratinocytes and disorganization of collagen fibers. At the same time, with clopidogrel administration, there was an improvement in the integrity of these structures. With venous congestion, nitroglycerin and BoTA treatments mitigated the epidermal and dermal injury; and clopidogrel caused coagulative necrosis. There was a significant increase in tissue gene expression and serum levels of vascular endothelial growth factor (VEGF) in ischemic flaps with BoTA and clopidogrel, nitroglycerin, and BoTA clopidogrel in flaps with venous congestion. With the 3 treatment agents, gene expression levels of tumor necrosis factor-α (TNF-α) were up-regulated in the flaps with ischemia and venous congestion. With all treatment modalities, its serum levels were significantly increased in flaps with venous congestion and significantly decreased in ischemic flaps. Our analyses suggest that the best treatment option for ischemic flaps is clopidogrel, while for flaps with venous congestion are nitroglycerin and BoTA.

Protective effects of Rosemary extract and/or Fluoxetine on Monosodium Glutamate-induced hippocampal neurotoxicity in rat.

The use of Monosodium Glutamate (MSG) as a food flavor enhancer is increasing worldwide despite its neurotoxic effects. Fluoxetine (FLX) and Rosemary extract (RE) are known to have beneficial neuroprotective properties. Rats were divided into five groups: control group; MSG group, rats received 2 g∕kg∕day intraperitoneal (i.p.) injections of MSG for seven days; RE/MSG group, rats received 50 mg∕kg∕day of oral RE for 28 days starting prior to MSG; FLX∕MSG group, rats received 10 mg∕kg∕day of oral FLX for 28 days beginning before MSG; and RE∕FLX∕MSG group, received combined treatments as mentioned above. Rats underwent the Barnes maze test, in addition to histopathological, immunohistochemical, morphometric and ultrastructural evaluations for their hippocampi. MSG increased the number of errors and escaped latency in the Barnes maze test that was significantly minimized in the three treatment groups. The MSG group exhibited pyramidal cell (PC) degeneration, shrunken glial cells and massive vascular dilatation that were improved with RE and∕or FLX treatment. The number of glial fibrillary acidic protein (GFAP)-immunopositive cells were increased, and the number of PCs was decreased in the MSG group, while these values were significantly reversed with the three treatment groups with the most significant improvement at RE∕FLX∕MSG one. Ultrastructurally, PCs were shrunken with degenerated nuclei, dilated endoplasmic reticulum, swollen mitochondria, and vacuolations in the MSG group that were improved with RE and∕or FLX. In conclusion, the combined RE and FLX treatment can ameliorate the toxic effect of MSG on rat hippocampus probably through its antioxidant and anti-inflammatory effects.

Granulocyte-colony stimulating factor improves intervertebral disc degeneration in experimental adult male rats: A microscopic and radiological study.

Intervertebral disc degeneration (IVDD) is a major contributor to low back pain (LBP). Granulocyte-colony stimulating factor (GCSF) is known to mobilize hematopoietic stem cells (HSCs) that may be implicated in intervertebral disc (IVD) regeneration. Rats were divided into the following three groups: (i) control group; (ii) IVDD group-the rats underwent Co5/Co6 and Co7/Co8 IVDD operation; and (iii) GCSF-treated group-the rats received daily GCSF subcutaneous injections starting 6 weeks after the IVDD operation and continued for 5 days. All of the rats were euthanized after 8 weeks, and IVDs were assessed by tail X-ray and histopathological, immunohistochemical, and transmission electron microscopy (TEM) analyses. The X-rays showed disc narrowing in the IVDD group that was significantly widened in the GCSF-treated rats. Histologically, the IVDD group showed disarrangement of the annulus fibrosis lamellae, complete degeneration of the nucleus pulposus, and loss of proteoglycan content. These changes were improved after GCSF treatment. Vertebral endplate thickness and cellularity were significantly decreased with IVDD and significantly increased after GCSF treatment. Stromal cell-derived factor-1α (SDF-1α) immune expression was significantly increased in the IVDD group but decreased in the GCSF-treated group. However, the caspase-3 expression percentage showed no significant difference among the studied groups. TEM showed excessive collagen deposits around the notochordal cells in the IVDD group, which were attenuated in the GCSF-treated group. These results indicate that GCSF improves IVDD and promotes its recovery based on radiological, histological and TEM findings.

Histopathological and biochemical alterations of the parotid gland induced by experimental hypothyroidism in adult male rats and the possible therapeutic effect of Nigella sativa oil.

Thyroid hormones are essential for metabolic rate regulation and play a role on the integrity of the salivary glands. Nigella sativa is a widely used plant in medicine. This study aimed to evaluate the effect of Nigella sativa oil (NSO) on the hypothyroidism-induced parotid gland pathological alterations. Rats were divided into four groups: control group, hypothyroid group: received daily oral carbimazole for 3 weeks, hypothyroid-NSO group: NSO was orally given for 4 weeks after hypothyroidism induction and NSO group: administrated NSO only for 4 weeks. After 7 weeks, all rats were sacrificed, serum thyroid hormones were estimated, and parotid glands were assessed by histopathological, immunohistochemical, ultrastructural and morphometric analyses. Hypothyroid group showed a significant decrease in thyroid hormones with increase in thyroid-stimulating hormone (TSH) levels and decrease in body and parotid weights compared to the control rats that were improved with NSO treatment. Sections of the hypothyroid group showed fibrosis, acinar cytoplasmic vacuolations, vascular congestion, ductal dilatation, wide intercellular canaliculi, nuclear pyknosis and decreased number of secretory granules. Also, there were decreased B-cell lymphoma 2 (Bcl-2) and increased p53, Bcl-2 Associated X (Bax) and alpha-smooth muscle actin (α-SMA) immune-expressions; with decreased Bax/ Bcl-2 ratio that all were attenuated by NSO. NSO ameliorates hypothyroidism-induced parotid changes by altering p53, Bax and Bcl-2 pathway.

The potential curative and preventive effects of garlic on testosterone-induced benign prostatic hyperplasia in orchiectomized rats.

Benign prostatic hyperplasia (BPH) is a common aging disease in men. Garlic is known to have anti-proliferative effects. Therefore, this study was designed to investigate the curative and preventive effects of garlic on BPH in rats. Rats were divided into five groups: control group, orchiectomized group (where rats were subjected to bilateral orchiectomies operation), BPH group [BPH was induced by intramuscular injection of testosterone (TE) enanthate once weekly for five weeks after orchiectomy], curative group (where rats were injected with TE for five weeks followed by daily administration of garlic powder for other five weeks), and preventive group (where rats were given garlic powder simultaneously with TE injections for five weeks). Serum levels of TE and prostate-specific antigen (PSA) were measured, and prostate weighed and processed for light microscopic, immunohistochemical and transmission electron microscopy (TEM) examination. Serum levels of TE and PSA, and prostate weight (PW) were significantly increased in BPH group and significantly decreased in curative and preventive ones. Histologically and morphometrically, BPH group showed epithelial hyperplasia, stromal expansion and reduced acinar lumens that were significantly improved in both curative and preventive groups. Proliferating cell nuclear antigen (PCNA) expression was increased while caspase-3 expression was decreased in BPH group. These results were reversed in both curative and preventive groups. TEM showed nuclear irregularities, dilated endoplasmic reticulum (ER) cisterns, and lost cell boundaries, secretory vesicles and apical microvilli. Most of the previous changes were minimized in preventive group more than in curative one.