The peri- and post-menopausal periods have been described as the “window of vulnerability” for the development of depressive symptoms that impair women activities and quality of life. The etiopathogenesis of these symptoms is multifactorial and may confer resistance to traditional antidepressants. Attention is now directed toward phytochemicals for their pleiotropic functions and safer profiles. This study investigated the possible perturbation of the nuclear factor erythroid 2–related factor 2 (Nrf2) signaling pathways as an underlying mechanism of post-ovariectomy depression and highlighted the potential benefits of carnosic acid (CA) on the associated behavioral, biochemical, and histopathological alterations. Female Balb/c mice were randomly assigned to be sham-operated or ovariectomized (OVX). After 3 weeks, OVX mice received either a vehicle, CA (20 mg/kg/day), or tin protoporphyrin IX (SnPP-IX; a heme oxygenase-1 (HO-1) inhibitor; 50 μmol/kg/day) for 3 weeks. Our findings revealed that OVX mice had depressive but not anxiety-like behavior. Suppressed Nrf2 and its downstream signaling, and augmented proinflammatory markers were observed in both the hippocampus and prefrontal cortex. CA treatment alleviated depressive behavior, induced the expression of Nrf2, HO-1, thioredoxin-1, and brain-derived neurotrophic factor, and enhanced serotonin levels. CA also suppressed oxidative stress, reduced TNF-α, IL-1β, and iNOS mRNA expression, and ameliorated OVX-induced histopathological changes. SnPP-IX aggravated post-OVX behavioral, neurobiochemical, and histological deteriorations, and reduced CA-protective effects. In conclusion, Nrf2/HO-1 signaling suppression and the associated proinflammatory state are key mechanisms in post-OVX depression. CA exerts multifaceted neuroprotection in OVX mice and represents a promising candidate for clinical evaluation as an antidepressant.

Diabetic nephropathy (DN) is one of the most common causes of chronic kidney diseases (CKDs) that have been associated with high morbidity and mortality.Recently, several studies have highlighted the protective role of vitamin D3 (VD3) and omega-3 fatty acids (O3-FAs) in CKDs. However, their effect on DN is still unclear.Aims: This study aimed to evaluate the effects of both VD3 and / or O3-FAs in slowing the progression of DN through their impact on indices of renal function, glycemic control, oxidative stress and markers of podocyte injury. Materials and methods: type I diabetes was induced in albino rats by single intraperitoneal injection of streptozotocin (65mg/kg). Rats received daily oral administration of VD3 and O3-FAs separately and in combination for 6 weeks. Results: VD3 and O3-FAs therapy improved significantly hyperglycemia, renal function tests, with concomitant decrease in total urinary protein content, urinary nephrin, a marker of podocyte injury and renal oxidative stress. However, the combined therapy was superior in its effect over VD3 and O3-FAs separately. Such results were confirmed by renal cortical tissue assessment using light microscopic examination of H&E and PAS stains in addition to transmission-electron microscopy. Conclusions: VD3 and O3-FAs have a potential beneficial effect on amelioration of structural changes in pedicels and glomerular basement membrane that was reflected as evident renal functional restoration.

Background With the widespread of Coronavirus Disease 2019 pandemic, in spite of the newly emerging vaccines, mutated strains remain a great obstacle to supportive and preventive measures. Coronavirus 19 survivors continue to face great danger of contacting the disease again. As long as no specific treatment has yet to be approved, a great percentage of patients experience real complications, including among others, lung fibrosis. High oxygen inhalation especially for prolonged periods is per se destructive to the lungs. Nevertheless, oxygen remains the first line support for such patients. In the present study we aimed at investigating the role of amniotic fluid-mesenchymal stem cells in preventing versus treating the hyperoxia-induced lung fibrosis in rats. Methods The study was conducted on adult albino rats; 5 pregnant female rats were used as amniotic fluid donors, and 64 male rats were randomly divided into two groups: Control group; where 10 rats were kept in normal atmospheric air then sacrificed after 2 months, and hyperoxia-induced lung fibrosis group, where 54 rats were exposed to hyperoxia (100% oxygen for 6 h/day) in air-tight glass chambers for 1 month, then randomly divided into the following 5 subgroups: Hyperoxia group, cell-free media-treated group, stem cells-prophylactic group, stem cells-treated group and untreated group. Isolation, culture and proliferation of stem cells were done till passage 3. Pulmonary function tests, histological examination of lung tissue under light and electron microscopes, biochemical assessment of oxidative stress, IL-6 and Rho-A levels, and statistical analysis of data were performed. F-test (ANOVA) was used for normally distributed quantitative variables, to compare between more than two groups, and Post Hoc test (Tukey) for pairwise comparisons. Results Labelled amniotic fluid-mesenchymal stem cells homed to lung tissue. Stem cells administration in the stem cells-prophylactic group succeeded to maintain pulmonary functions near the normal values with no significant difference between their values and those of the control group. Moreover, histological examination of lung tissues showed that stem cells-prophylactic group were completely protected while stem cells-treated group still showed various degrees of tissue injury, namely; thickened interalveolar septa, atelectasis and interstitial pneumonia. Biochemical studies after stem cells injection also showed decreased levels of RhoA and IL-6 in the prophylactic group and to a lesser extent in the treated group, in addition to increased total antioxidant capacity and decreased malondialdehyde in the stem cells-injected groups. Conclusions Amniotic fluid-mesenchymal stem cells showed promising protective and therapeutic results against hyperoxia-induced lung fibrosis as evaluated physiologically, histologically and biochemically.

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ID 18929 Poster Board 421Skeletal muscle ischemia and reperfusion (S-I/R) is frequently associated with aggravated inflammatory response and tissue injury that could be relieved by interventions like remote ischemic preconditioning (RIPC) or the hormonal growth factor erythropoietin (EPO). Here, we tested the hypotheses that (i) the simultaneous exposure to a low dose of EPO boosts the protection conferred by RIPC against S-I/R injury, and (ii) this privileged EPO/RIPC effect is prompted by mitochondrial and extra-mitochondrial machineries. The effects of RIPC, EPO (500 or 5000 IU/kg), or combined RIPC/EPO-500 regimen on S-I/R injury induced by right hindlimb 3-hr ischemia for followed by 3-hr reperfusion were investigated. RIPC was induced by 3 brief consecutive I/R cycles (10-min ischemia and 10-min reperfusion each) of the contralateral hindlimb. S-I/R injury was verified by the (i) rise in serum lactate dehydrogenase, pyruvate, and creatine kinase, (ii) histopathological signs of sarcoplasm vacuolations, segmental necrosis, and inflammatory cells infiltration, and (iii) increments and decrements in electromyographic amplitude and duration, respectively. These defects were partially ameliorated by RIPC or by EPO in a dose-related fashion. Further, greater repairs of functional/structural anomalies of S-I/R were seen in rats pre-exposed to the combined RIPC/EPO-500 intervention. The latter therapy also caused more effective preservation of the number of MitoTracker red-stained mitochondria assessed by confocal microscopy and suppression of mitochondrial DNA damage and indices of oxidative stress and apoptosis like cardiolipin, succinate dehydrogenase, citrate synthase, and cytochrome c. Additionally the combined RIPC/EPO therapy was more influential than individual treatments in ameliorating rises in muscular myeloperoxidase and nitric oxide metabolites and preventing excessive calcium accumulation and glycogen consumption. Overall, the dual RIPC/EPO therapy additively mends mitochondrial dysfunction and interrelated skeletal structural and functional deficits induced by S-I/R injury. The use of relatively low EPO doses might serve to minimize adverse effects often encountered with the clinical use of the hormone