Arginine metabolic pathways determine its therapeutic benefit in experimental heatstroke: Role of Th1/Th2 cytokine balance

Chatterjee, Saurabh; Premachandran, Sudha; Bagewadikar, R. S.; Bhattacharya, Saurav; Chattopadhyay, Subrata; Poduval, T. Balakrishna

doi:10.1016/j.niox.2006.04.003

Cited by 43 publications

(43 citation statements)

References 30 publications

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“…Inflammatory surges in many diseases are accompanied by a late M2 shift, which can arise from higher proinflammatory cytokine levels, higher NO levels, or both (Liu et al, 2014). High NO levels have been accompanied by higher arginase activity, leading to release of transforming growth factor-b, IL-4, and IL-13, which are primarily anti-inflammatory but do contribute to the fibrotic process (Chatterjee et al, 2006;Liu et al, 2014). The role of higher NO levels in causing a feedback loop triggering anti-inflammatory mechanisms can be a potential therapeutic approach in NASH, given the use of an NO donor in a single study for NASH remediation involving ob/ob mice, the spontaneous knockout (KO) of leptin, where no mechanistic inputs were provided (de Oliveira et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

M1 Polarization Bias and Subsequent Nonalcoholic Steatohepatitis Progression Is Attenuated by Nitric Oxide Donor DETA NONOate via Inhibition of CYP2E1-Induced Oxidative Stress in Obese Mice

Seth

Das

Pourhoseini

et al. 2014

J Pharmacol Exp Ther

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Activation of M1 macrophages in nonalcoholic steatohepatitis (NASH) is produced by several external or endogenous factors: inflammatory stimuli, oxidative stress, and cytokines are known. However, any direct role of oxidative stress in causing M1 polarization in NASH has been unclear. We hypothesized that CYP2E1-mediated oxidative stress causes M1 polarization in experimental NASH, and that nitric oxide (NO) donor administration inhibits CYP2E1-mediated inflammation with concomitant attenuation of M1 polarization. Because CYP2E1 takes center stage in these studies, we used a toxin model of NASH that uses a ligand and a substrate of CYP2E1 for inducing NASH. Subsequently, we used a methionine and choline-deficient diet-induced rodent NASH model where the role of CYP2E1 in disease progression has been shown. Our results show that CYP2E1 causes M1 polarization bias, which includes a significant increase in interleukin-1b (IL-1b) and IL-12 in both models of NASH, whereas CYP2E1-null mice or diallyl sulfide administration prevented it. Administration of gadolinium chloride (GdCl 3 ), a macrophage toxin, attenuated both the initial M1 response and the subsequent M2 response, showing that the observed increase in cytokine levels is primarily from macrophages. Based on the evidence of an adaptive NO increase, the NO donor administration in vivo that mechanistically inhibited CYP2E1 catalyzed the oxidative stress during the entire study in NASHabrogated M1 polarization and NASH progression. The results obtained show the association of CYP2E1 in M1 polarization, and that inhibition of CYP2E1 catalyzed oxidative stress by an NO donor (DETA NONOate [(Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino]diazen-1-ium-1,2-diolate]) can be a promising therapeutic strategy in NASH.

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Section: Introductionmentioning

confidence: 99%

M1 Polarization Bias and Subsequent Nonalcoholic Steatohepatitis Progression Is Attenuated by Nitric Oxide Donor DETA NONOate via Inhibition of CYP2E1-Induced Oxidative Stress in Obese Mice

Seth

Das

Pourhoseini

et al. 2014

J Pharmacol Exp Ther

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“…As heat stress continues, hypoxic cells can produce multiorgan dysfunction and inflammation. Although the severity of heatstroke depends on the degree of hyperthermia and its duration [14] , normal volunteers can passively endure a core temperature of about 42 °C with none or minimal tissue injury [15,16] . Indeed, as demonstrated in the present results, KYNA treatment significantly prevented the occurrence of heat-induced multi-organ damage and inflammation without .05 in comparison with NT group; e P<0.05 in comparison with (VEH+HS) group.…”

Section: Discussionmentioning

confidence: 99%

Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke

Hsieh

Chen

Yeh³

et al. 2011

Acta Pharmacol Sin

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IntroductionHeatstroke is defined as a form of excessive hyperthermia (>40 °C) associated with a systemic inflammatory response that leads to multi-organ dysfunction in which central nervous system (CNS) disorders such as delusion, convulsion and coma predominate [1] . Our recent results have demonstrated that heatstroke rodents display hypotension, systemic inflammatory responses, hypothalamic ischemia and neuronal damage, and multi-organ dysfunction [2][3][4] .Kynurenic acid (KYNA) or its metabolic precursor L-kynurenine may be of therapeutic value in neurodegenerative diseased models [5,6] . For example, systemically administered high doses of KYNA had a neuroprotective effect in the gerbil model of global ischemia [7] . Both the homocysteine-induced impairment of endothelial cells [8] and the motility and inflammatory activation in the early phase of acute experimental colitis in the rat [9] were significantly reduced by administration of KYNA. The aim of this study was to investigate whether the heatstroke induced hypotension, systemic inflammatory responses, hypothalamic ischemia and damage, and multiorgan dysfunction could be attenuated by KYNA preconditioning. Accordingly, the temporal profiles of the apoptotic cell numbers of spleen, kidney, liver, lung, and hypothalamus, Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke Aim: To assess whether systemic delivery of kynurenic acid improves the outcomes of heatstroke in rats. Methods: Anesthetized rats were divided into 2 major groups and given vehicle solution (isotonic saline 0.3 mL/kg rat weight) or kynurenic acid (30-100 mg in 0.3 mL saline/kg) 4 h before the start of thermal experiments. They were exposed to an ambient temperature of 43 ºC for 68 min to induce heatstroke. Another group of rats were exposed to room temperature (26 ºC) and used as normothermic controls. Their core temperatures, mean arterial pressures, serum levels of systemic inflammatory response molecules, hypothalamic values of apoptotic cells and neuronal damage scores, and spleen, liver, kidney and lung values of apoptotic cells were determined. Results: The survival time values during heatstroke for vehicle-treated rats were decreased from the control values of 475-485 min to new values of 83-95 min. Treatment with KYNA (30-100 mg/kg, iv) 4 h before the start of heat stress significantly and dose-dependently decreased the survival time to new values of 152-356 min (P<0.05). Vehicle-treated heatstroke rats displayed hypotension, hypothalamic neuronal degeneration and apoptosis, increased serum levels of tunor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and interleukin-10 (IL-10), and spleen, liver, kidney, and lung apoptosis. KYNA preconditioning protected against hypotension but not hyperthermia and attenuated hypothalamic neuronal degeneration and apoptosis during heatstroke. KYNA preconditioning attenuated spleen, kidney, liver, and lung apoptosis and up-regulated serum IL-10 levels but down-regulated serum TNF-α and ICAM-1 lev...

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“…According to the findings of Chatterjee et al (5,6), WBH-treated mice were unable to maintain their normal thermoregulation. When they were exposed to room temperature (26°C), they displayed thermoregulatory deficits (e.g., hypothermia).…”

Section: Assessment Of Thermoregulatory Functionmentioning

confidence: 98%

“…ICR male mice 8 to 10 weeks old were exposed to WBH (41.2°C, relative humidity 50-55%, for 1 h) in an environmental temperature-controlled chamber (5,6,9). The heated mice were returned to the normal room temperature (26°C) after the end of WBH.…”

Section: Murine Model Of Heatstrokementioning

confidence: 99%

Transplantation of Human Dental Pulp-Derived Stem Cells Protects against Heatstroke in Mice

et al. 2015

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Stem cells from human exfoliated deciduous tooth pulp (SHED) is a promising approach for the treatment of stroke and spinal cord injury. In this study, we investigated the therapeutic effects of SHED for the treatment of multiple organ (including brain, particularly hypothalamus) injury in heatstroke mice. ICR male mice were exposed to whole body heating (WBH; 41.2°C, relative humidity 50-55%, for 1 h) and then returned to normal room temperature (26°C). We observed that intravenous administration of SHED immediately post-WBH exhibited the following therapeutic benefits for recovery after heatstroke: (a) inhibition of WBH-induced neurologic and thermoregulatory deficits; (b) reduction of WBH-induced ischemia, hypoxia, and oxidative damage to the brain (particularly the hypothalamus); (c) attenuation of WBH-induced increased plasma levels of systemic inflammatory response molecules, such as tumor necrosis factor-a and intercellular adhesion molecule-1; (d) improvement of WBH-induced hypothalamo-pituitary-adrenocortical (HPA) axis activity (as reflected by enhanced plasma levels of both adrenocorticotrophic hormone and corticosterone); and (e) attenuation of WBHinduced multiple organ apoptosis as well as lethality. In conclusion, post-WBH treatment with SHED reduced induction of proinflammatory cytokines and oxidative radicals, enhanced plasma induction of both adrenocorticotrophic hormone and corticosterone, and improved lethality in mouse heatstroke. The protective effect of SHED may be related to a decreased inflammatory response, decreased oxidative stress, and an increased HPA axis activity following the WBH injury.

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Arginine metabolic pathways determine its therapeutic benefit in experimental heatstroke: Role of Th1/Th2 cytokine balance

Cited by 43 publications

References 30 publications

M1 Polarization Bias and Subsequent Nonalcoholic Steatohepatitis Progression Is Attenuated by Nitric Oxide Donor DETA NONOate via Inhibition of CYP2E1-Induced Oxidative Stress in Obese Mice

M1 Polarization Bias and Subsequent Nonalcoholic Steatohepatitis Progression Is Attenuated by Nitric Oxide Donor DETA NONOate via Inhibition of CYP2E1-Induced Oxidative Stress in Obese Mice

Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke

Transplantation of Human Dental Pulp-Derived Stem Cells Protects against Heatstroke in Mice

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