Sitagliptin Attenuates the Cognitive Deficits in L-Methionine-Induced Vascular Dementia in Rats.

Vascular dementia (VaD) is the second most prevalent type of dementia characterized by progressive cognitive deficits and is a major risk factor for the development of Alzheimer's disease and other neurodegenerative disorders. This study is aimed at determining the potential neuroprotective effect of sitagliptin (STG) on cognitive deficits in L-methionine-induced VaD in rats and the possible underlying mechanisms. 30 adult male Wistar albino rats were divided equally (n = 10) into three groups: control, VaD, and VaD + STG groups. The cognitive performance of the animals was conducted by open field, elevated plus maze, Y-maze, novel object recognition, and Morris water maze tests. Serum homocysteine, TNF-α, IL-6, IL-10, total cholesterol, and triglycerides levels were assessed together with hippocampal MDA, SOD, and BDNF. Histopathological and immunohistochemical assessments of the thoracic aorta and hippocampus (CA1 region) were also performed. Chronic L-methionine administration impaired memory and learning and induced anxiety. On the other hand, STG protected against cognitive deficits through improving oxidative stress biomarkers, inflammatory mediators, lipid profiles, and hippocampus level of BDNF as well as decreasing caspase-3 and GFAP and increasing Ki-67 immunoreactions in the hippocampus. Also, STG improved the endothelial dysfunction via upregulation of aortic eNOS immunoreaction. STG improved the cognitive deficits of L-methionine-induced VaD by its antioxidant, anti-inflammatory, antiapoptotic, and neurotrophic effects. These findings suggest that STG may be a promising future agent for protection against VaD.

Treadmill Exercise Training Ameliorates Functional and Structural Age-Associated Kidney Changes in Male Albino Rats.

Aging is a biological process that impacts multiple organs. Unfortunately, kidney aging affects the quality of life with high mortality rate. So, searching for innovative nonpharmacological modality improving age-associated kidney deterioration is important. This study aimed to throw more light on the beneficial effect of treadmill exercise on the aged kidney. Thirty male albino rats were divided into three groups: young (3-4 months old), sedentary aged (23-24 months old), and exercised aged (23-24 months old, practiced moderate-intensity treadmill exercise 5 days/week for 8 weeks). The results showed marked structural alterations in the aged kidney with concomitant impairment of kidney functions and increase in arterial blood pressure with no significant difference in kidney weight. Also, it revealed that treadmill exercise alleviated theses effects in exercised aged group with reduction of urea and cystatin C. Exercise training significantly decreased glomerulosclerosis index, tubular injury score, and % area of collagen deposition. Treadmill exercise exerted its beneficial role via a significant reduction of C-reactive protein and malondialdehyde and increase in total antioxidant capacity. In addition, exercise training significantly decreased desmin immunoreaction and increased aquaporin-3, vascular endothelial growth factor, and beclin-1 in the aged kidney. This study clarified that treadmill exercise exerted its effects via antioxidant and anti-inflammatory mechanisms, podocyte protection, improving aquaporin-3 and vascular endothelial growth factor expression, and inducing autophagy in the aged kidney. This work provided a new insight into the promising role of aerobic exercise to ameliorate age-associated kidney damage.

Controlled ozone therapy modulates the neurodegenerative changes in the frontal cortex of the aged albino rat.

Aging is a normal process associated with neurodegenerative changes resulting in decline of cognitive and motor functions. Oxidative stress plays an important role. Controlled ozone (O3) therapy has been proved to induce oxidative preconditioning thus reversing oxidative stress. To the best of our knowledge, this research is the first attempt to investigate whether the antioxidant properties of O3 can ameliorate age-associated structural alterations of the cerebral cortex. Ozone administration (at a dose of 0.7mg/kg intraperitonially, three times a week for eight weeks) produced significant downregulation of tissue malondialdehyde (MDA) and upregulation of glutathione, superoxide dismutase (SOD) and catalase (CAT) within the frontal cortex of aged rats. Sections of the frontal cortex from adult and aged rats were stained with hematoxylin and eosin and analyzed using light microscopy. In addition, quantitative immunohistochemical assessments of the expression of inducible nitric oxide synthase (iNOS), caspase-3, glial fibrillary acidic protein (GFAP), Ki67 and acetylcholinesterase (AChE) were performed. Our results revealed the beneficial effect of O3 in improving the neurodegenerative changes of the cerebral cortex of aged rats. Moreover, this study clarified that O3 exerted its effects via reducing oxidative stress, apoptosis, gliosis as well as improving neurogenesis and cholinergic plasticity. This work added to the previously proved aging - associated neurodegenerative effects and provided a new insight into the promising role of O3 to ameliorate these effects.

Evaluation of testicular cytotoxicity and genotoxicity of sofosbuvir and sofosbuvir - ribavirin in the adult male albino rats

Hepatitis C is a widely distributed problem all over the world, especially Egypt. Chronically infected people develop serious liver disease and now it is the most common cause for liver transplantation. Recently, a new regimen, sofosbuvir (sovaldi), alone or with combinations as sovaldi-ribavirin, was approved for treating this disease. There are limited studies that explore the effects of these drugs on the reproductive organs, and hence affection of male fertility while using these drugs. This study aims to throw more light on whether sovaldi or sovaldi-ribavirin causes testicular damaging effects in the adult male albino rats. We investigated the effect of this regimen in a dose equivalent to that used in the human (41 mg/kg once daily orally for sovaldi and 41 mg/kg twice daily orally for ribavirin) for consecutive 5 and 10 days. There was highly significant decrease in testosterone hormone level and marked degenerative changes in the seminiferous tubules and the testicular interstitium, with increase in collagen deposits in sovaldi treated rats, and in a more extensive manner in sovaldi-ribavirin treated rats. There was a significant increase of deoxyribonucleic acid (DNA) fragmentation in the treated groups after 10 days. However, there was a non-significant difference in DNA fragmentation in the treated groups after 5 days when compared with control. Immuno-histochemistry detection of caspase-3 showed significant increase in its expression in the treated groups after either 5 or 10 days. This denoted the specificity of caspase-3 immunohistochemistry technique in the detection of early apoptotic changes. It was concluded that sovaldi and sovaldi ribavirin induced gonado toxic effects through induction of DNA fragmentation via up regulation of caspase-3, and that the resulting damaging effects increased with longer duration of drug in take

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Protective role of broccoli extract on estradiol valerate-induced polycystic ovary syndrome in female rats

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility. The aim of this study was to investigate the protective role of broccoli extract on estradiol valerate (EV)-induced PCOS in female rats. Forty adult female rats were divided into four main groups; control, broccoli-treated, EV, single intramuscular injection of 16mg/kg)-treated, EV+broccoli (1 g/kg/day)-treated groups. The protected rats were treated orally by gastric tube daily for 4 weeks. At the end of the experiment, blood samples were collected and the ovary were subjected to histological and immunohistochemical analyses. EV treated group exhibited the characteristic features of PCOS. Disturbed ovarian cyclicity in addition to histopathological alterations, including decreased number of healthy follicles and corpora lutea, increased degenerated, cystic follicles and increased collagen fiber deposition were detected by light microscopic studies. Moreover, increased immune-reactivity for iNOS and altered proliferation index were observed by immunohistochemical assessments. Co-adminis-tration of broccoli extract improved EV-induced PCOS in rat model. In conclusion, broccoli may be an effective therapeutic candidate for the treatment of PCOS

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