Postconditioning is protective in renal reperfusion injury only in male rats. A gender difference study

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Research paper: Dalteparin as a novel therapeutic agent to prevent diabetic encephalopathy by targeting oxidative stress and inflammation

Introduction: Hepcidin is the main modulator of systemic iron metabolism, and its role in the brain has been clarified recently. Studies have shown that hepcidin plays an important role in neuronal iron load and inflammation. This issue is of significance because neuronal iron load and inflammation are pathophysiological processes that are highly linked to neurodegeneration. Moreover, the activity of hepcidin has recently been manipulated to recover the neuronal impairment caused by brain inflammation in animal models. Methods: Streptozotocin (STZ) was used to induce type 1 diabetes. Male Wistar rats (n = 40) with a weight range of 200-250 g were divided into control, diabetic, diabetic + insulin, and diabetic + dalteparin groups. Dalteparin (100 mg/kg IP) and insulin (100 mg/kg SC) were administered for 8 weeks. At the end of the experiment, Y-maze and passive avoidance tasks were carried out. The animals were perfused randomly and their hippocampal tissue was isolated for the analysis of markers such as lipid peroxidation like Malondialdehyde (MDA), hepcidin expression, iron, and ferritin. Blood samples were taken for the measurement of serum inflammatory cytokine Interleukin (IL)-6. Results: The findings indicated that treatment with dalteparin reduced IL-6, MDA, ferritin, and hepcidin expression in diabetic rats compared to treatment with insulin (P<0.05). Moreover, treatment with dalteparin did not decrease the iron level or prevented its decline. Conclusion: Treatment with dalteparin improved the cognitive dysfunctions and symptoms of Alzheimer disease in STZ-induced diabetic rats by appropriately modulating and reducing oxidative stress and neuroinflammation. This may enhance the existing knowledge of therapeutics to reduce cognitive impairment in diabetes and is suggested to be a potential therapeutic agent in diabetes. © 2020 Iran University of Medical Sciences. All rights reserved

Beneficial effects of Se/Zn co-supplementation on body weight and adipose tissue inflammation in high-fat diet-induced obese rats

This research investigated the effect of co-supplementation of selenium with zinc on weight control and the inflammatory and oxidative status in relation to obesity. Male Wistar rats (N = 32) were randomly divided into four groups after induction of obesity model: 1) �Zn� was supplemented with zinc sulfate (15 mg/kg BW), 2) �Se� supplemented with selenium as sodium selenate (0.5 mg/kg BW), 3) �Zn + Se� which received Zn (15 mg/kg BW) + Se (0.5 mg/kg BW), and 4) �HFD� as the control group. The intervention was done for eight weeks. At the end of treatment, serum and tissue level of Zn, Se, SOD, GSH-Px, MDA, leptin, TNF-α, and IL-6 was evaluated. Weight and food intake were significantly reduced in the Se group(p <.001), while in the Zn group, weight gain due to obesity was prevented compared to the control group (p =.48). There was a significant and stronger increase in SOD, GSH-Px levels and a remarkable decrease in MDA, leptin, TNF-α, and IL-6 in the group receiving the combination of two supplements than either alone(p <.001). Leptin had a positive correlation with inflammatory factors and lipid peroxidation marker and showed an inverse relationship with Zn and Se levels and anti-oxidative enzymes(p <.05). The analysis showed the mediating role of leptin in the effects of zinc. Co-supplementation of selenium and zinc may have a synergistic effect in reduction of oxidative and inflammatory markers. Regarding the effect of zinc on inflammatory factors and lipid peroxidation, leptin can play a mediating role. © 2021 The Authors. Food Science & Nutrition published by Wiley Periodicals LL

Evaluation of the neuroprotective effects of electromagnetic fields and coenzyme Q 10 on hippocampal injury in mouse

Electromagnetic fields (EMFs) are reported to interfere with chemical reactions involving free radical production. Coenzyme Q 10 (CoQ10) is a strong antioxidant with some neuroprotective activities. The purpose of this study was to examine and compare the neuroprotective effects of EMF and CoQ10 in a mouse model of hippocampal injury. Hippocampal injury was induced in mature female mice (25–30 g), using an intraperitoneal injection of trimethyltin hydroxide (TMT; 2.5 mg/kg). The experimental groups were exposed to EMF at a frequency of 50 Hz and intensity of 5.9 mT for 7 hr daily over 1 week or treated with CoQ10 (10 mg/kg) for 2 weeks following TMT injection. A Morris water maze apparatus was used to assess learning and spatial memory. Nissl staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) tests were also performed for the histopathological analysis of the hippocampus. Antiapoptotic genes were studied, using the Western blot technique. The water maze test showed memory improvement following treatment with CoQ10 and coadministration of CoQ10 + EMF. The Nissl staining and TUNEL tests indicated a decline in necrotic and apoptotic cell count following treatment with CoQ10 and coadministration of CoQ10 + EMF. The Western blot study indicated the upregulation of antiapoptotic genes in treatment with CoQ10, as well as coadministration. Also, treatment with EMF had no significant effects on reducing damage induced by TMT in the hippocampus. According to the results, EMF had no significant neuroprotective effects in comparison with CoQ10 on hippocampal injury in mice. Nevertheless, coadministration of EMF and CoQ10 could improve the neuroprotective effects of CoQ1

Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota

Gut microbiota-related metabolites are potential clinical biomarkers for cardiovascular disease (CVD). Circulating succinate, a metabolite produced by both microbiota and the host, is increased in hypertension, ischemic heart disease, and type 2 diabetes. We aimed to analyze systemic levels of succinate in obesity, a major risk factor for CVD, and its relationship with gut microbiome. We explored the association of circulating succinate with specific metagenomic signatures in cross-sectional and prospective cohorts of Caucasian Spanish subjects. Obesity was associated with elevated levels of circulating succinate concomitant with impaired glucose metabolism. This increase was associated with specific changes in gut microbiota related to succinate metabolism: a higher relative abundance of succinate-producing Prevotellaceae (P) and Veillonellaceae (V), and a lower relative abundance of succinate-consuming Odoribacteraceae (O) and Clostridaceae (C) in obese individuals, with the (P + V/O + C) ratio being a main determinant of plasma succinate. Weight loss intervention decreased (P + V/O + C) ratio coincident with the reduction in circulating succinate. In the spontaneous evolution after good dietary advice, alterations in circulating succinate levels were linked to specific metagenomic signatures associated with carbohydrate metabolism and energy production with independence of body weight change. Our data support the importance of microbe-microbe interactions for the metabolite signature of gut microbiome and uncover succinate as a potential microbiota-derived metabolite related to CVD risk