• 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • FITC, Fluorescein isothiocyanate australia It has been well


    It has been well established that shortly after systemic inflammation, NADPH oxidase and iNOS activity were increased in the FITC, Fluorescein isothiocyanate australia and lead to overproduction of reactive oxygen species (ROS) and NO [66]. Moreover, previous studies indicated that Ang II induced an increased level of NADPH oxidase and iNOS activities during inflammation by stimulating of AT1R to promote oxidative stress [14]. It seems that the role of Ang II was very bold in this process since in this study we observed that inhibition of AT1R by 3 mg/kg losartan completely blocked oxidative stress. It has been reported that there is a cross-talk between TLR4 and AT1R which is elucidated by an evidence that in TLR4-deficient mice, Ang II was unable to induce microglial activation or ROS production within the paraventricular nucleus (PVN) of the hypothalamus [67]. AT1Rs are expressed FITC, Fluorescein isothiocyanate australia in microglia, neurons and astrocytes. Previous studies demonstrated that under neuropathological conditions such as epilepsy, neurodegenerative disease and inflammation the expression of AT1Rs are increased in the activated microglia [20]. Also AT1Rs are highly expressed in the cerebrovascular endothelial cells and circumventricular organs that can be also activated with circular Ang II [10]. In addition, elevated circulating levels of Ang II also can disrupt the BBB integrity, allowing the access of circulating Ang II to the brain parenchyma and direct stimulation of the AT1R in the brain [68]. While, AT1R has an important role in the controlling of homeostasis, excessive and unregulated AT1R stimulation is one of the most important inflammation and oxidative stress inducer and there is an extensive evidence indicating the role of AT1R in the developing of neurodegenerative diseases [10,69]. There are several mechanisms by which ARBs ameliorates brain inflammation including, inhibition of nuclear translocation of nuclear factor-κB (NF-кB) [15,22,25], prevention from NADPH oxidase activation [14,15] and reduction of ROS, cyclooxygenase-2 (COX2) and prostaglandin E2 (PGE2) production [25,70]. ARBs also attenuate iNOS activity [14] and pro-inflammatory cytokines production [17,25] and protect against the BBB breakdown [71,72]. Also ARBs are able to increase the anti-inflammatory IL-10 production [25]. On the other hand, blocking of AT1R leads to conversion of excess endogenous Ang II to Ang IV that then active AT4R [73] or increase stimulation of AT2R by excess endogenous Ang II [25,74,75] which both have neuroprotective effects. In this study, at least, a part of beneficial effects of losartan may also arise from its ability to modulation of peripheral inflammation. However, when administrated systemically, ARBs are able to penetrate to the brain and directly block the brain AT1Rs [10,76]. Moreover, in models of inflammation that were just limited to the brain, systemic administrations of ARBs were effectively able to inhibit the brain inflammation [19,26]. Also, losartan can have specific effects beyond the anti-inflammatory effects in the LPS group which is most be tested in control group, however, previous studies reported that losartan when administrated in a control group had no significant effects compare to control group [20,77].
    Conflict of interest
    Acknowledgments The results described in this paper were from a PhD student's thesis. The authors would like to thank the Vice Presidency of Research of Mashhad University of Medical Sciences for their financial support (NO: 941089 and 9161249).
    Introduction Metabolic syndrome is a rising epidemic in the western world and is characterized by the simultaneous presence of hypertension, dyslipidemia, elevated fasting plasma glucose levels, abdominal obesity, and insulin resistance [11]. Insulin resistance (IR) is a hallmark for the progression of type II diabetes and causes an incomplete uptake of circulating plasma glucose due to impaired insulin secretion and/or receptor signaling [1]. Inappropriate activation of the renin-angiotensin system (RAS) through the angiotensin II type I (AT1) receptor occurs during insulin resistance and has been implicated in contributing to cardiovascular derangements not limited to vasoconstriction, thrombosis, and cardiovascular remodeling [9]. Mitochondrial dysfunction contributes to heart disease, and may contribute disproportionately to the accumulation of oxidative damage during diabetes [2,19]. Furthermore, cardiomyocytes contain larger amounts of mitochondria compared to other tissues [27], while the heart as a whole contains a lower antioxidant capacity [33] which increases its susceptibility to mitochondria-derived oxidation. In turn, mitochondrial oxidation increases oxidant generation further burdening antioxidant enzymes, which may lessen their ability to correct the oxidant imbalance [14]. Furthermore, mitochondrial and antioxidant dysfunctions may be exacerbated by post-prandial glucose mediated oxidant production in insulin resistant individuals [3,34]. Among the enzymes that are altered by oxidized conditions are aconitase, and in the citric acid cycle, NADH dehydrogenase (complex I), succinate dehydrogenase (complex II), and cytochrome c reductase (complex III) [4,22].