Improved Functional Recovery of Ischemic Rat Hearts due to Singlet Oxygen Scavengers Histidine and Carnosine

Lee, John W.; Mikami, Hiroshi; Bobst, Elisabeth V.; Hester, Jeff; Ashraf, Muhammad; Bobst, Albert M.

doi:10.1006/jmcc.1998.0850

Cited by 82 publications

(53 citation statements)

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“…8). These observations suggest that consistent with previous work (24), carnosine attenuates myocardial ischemia-reperfusion injury but both AR and carnosine are required for the manifestation of the cardioprotective effects of carnosine.…”

Section: Carnosine-aldehyde Metabolites In Human Urine-previoussupporting

confidence: 91%

“…This view is consistent with the observation that perfusion with carnosine improved myocardial recovery after ischemia. The beneficial effects of carnosine against ischemic injury have been described before (24); however, the mechanisms by which carnosine exerts its antiischemic effects are not known. It has been speculated that carnosine could protect against ischemia by buffering changes in intracellular pH, by increasing the calcium sensitivity of the myofilaments, or by quenching singlet oxygen (23).…”

Section: Discussionmentioning

confidence: 99%

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Role of Aldose Reductase in the Metabolism and Detoxification of Carnosine-Acrolein Conjugates

Baba

Hoetker

Merchant

et al. 2013

Journal of Biological Chemistry

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Background: Lipid peroxidation generates unsaturated aldehydes that form conjugates with histidyl dipeptides. Results: Carnosine-aldehyde conjugates form covalent adducts with proteins and are reduced by aldose reductase. Conclusion: Detoxification of carnosine-aldehyde by aldose reductase prevents protein carnosinylation. Significance: Aldose reductase prevents tissue injury due to aldehyde-carnosine conjugates.

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Section: Carnosine-aldehyde Metabolites In Human Urine-previoussupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Role of Aldose Reductase in the Metabolism and Detoxification of Carnosine-Acrolein Conjugates

Baba

Hoetker

Merchant

et al. 2013

Journal of Biological Chemistry

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“…Thus, improved insulin sensitivity and alleviation of inflammation and oxidative stress could be due to the increased serum histidine. Histidine is a free radical scavenger and can chelate divalent metal ions [23,24]. Its effects against oxidative stress have been well investigated in animals and cells.…”

Section: Discussionmentioning

confidence: 99%

Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial

et al. 2013

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Aims/hypothesis Increased inflammation and oxidative stress are associated with insulin resistance (IR) and metabolic disorders. Serum histidine levels are lower and are negatively associated with inflammation and oxidative stress in obese women. The objective of this study was to evaluate the efficacy of histidine supplementation on IR, inflammation, oxidative stress and metabolic disorders in obese women with the metabolic syndrome (MetS). Methods A total of 100 obese women aged 33-51 years with BMI≥28 kg/m 2 and diagnosed with MetS were included following a health examination in the community hospital in this randomised, double-blinded, placebo-controlled trial. Participants were allocated to interventions by an investigator using sequentially numbered sealed envelopes and received 4 g/day histidine (n=50) or identical placebo (n=50) for 12 weeks. Participants then attended the same clinic every 2 weeks for scheduled interviews and to count tablets returned. Serum histidine, HOMA-IR, BMI, waist circumference, fat mass, serum NEFA, and variables connected to inflammation and oxidative stress were measured at baseline and 12 weeks. Participants, examining physicians and investigators assessing the outcomes were blinded to group assignment. In addition, the inflammatory mechanisms of histidine were also explored in adipocytes. CI 0.60, 3.44] in histidine supplementation group (n=45), respectively. There were significant correlations between changes in serum histidine and changes of IR and its risk factors. No side effects were observed during the intervention. In vitro study indicated that histidine suppresses IL6 and TNF mRNA expression and nuclear factor kappa-B (NF-κB) protein production in palmitic acid-induced adipocytes in a dose-dependent manner, and these changes were diminished by an inhibitor of NF-κB. Conclusions/interpretation Histidine supplementation could improve IR, reduce BMI, fat mass and NEFA and suppress inflammation and oxidative stress in obese women with MetS; histidine could improve IR through suppressed pro-inflammatory cytokine expression, possibly by the NF-κB pathway, in adipocytes. Trial registration www.chictr.org/cn/ChiCTR-TRC-11001551Electronic supplementary material The online version of this article

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“…Of course, several hypotheses have been proposed, such as that carnosine acts as a buffering agent in the skeletal muscle and as a neurotransmitter and antioxidant, as recently reviewed by Hipkiss (2009). Moreover, in vitro and animal studies strongly suggest that carnosine is able to restrain some oxidative-based diseases such as diabetes Lee et al 2005;Pfister et al 2011), atherosclerosis (Rashid et al 2007) and metabolic distress syndrome , and also ischemia-reperfusion damage in different organs, including the brain (Pekcetin et al 2009;Dobrota et al 2005) and the heart (Lee et al 1999). Such a protective effect has been initially put down to the antioxidant and metal ion chelating ability of carnosine (Klebanov et al 1998), as well to a pro-histaminic effect, this latter mainly taken into account to explain the anti-ischemic effect (Kurata et al 2006).…”

Section: Introductionmentioning

confidence: 96%

Transforming dietary peptides in promising lead compounds: the case of bioavailable carnosine analogs

Vistoli

Carini

2012

Amino Acids

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The ability of carnosine to prevent advanced glycoxidation end products (AGEs) and advanced lipoxidation end products (ALEs) formation, on the one hand, and the convincing evidence that these compounds act as pathogenetic factors, on the other hand, strongly support carnosine as a promising therapeutic agent for oxidative-based diseases. The mechanism/s by which carnosine inhibits AGEs and ALEs is still under investigation but an emerging hypothesis is that carnosine acts by deactivating the AGEs and ALEs precursors and in particular the reactive carbonyl species (RCS) generated by both lipid and sugar oxidation. The ability of carnosine to inhibit AGEs and ALEs formation and the corresponding biological effects has been demonstrated in several in vitro studies and in some animal models. However, such effects are in line of principle, limited in humans, due to the effect of serum carnosinase (absent in rodents), which catalyzes the carnosine hydrolysis to its constitutive amino acids. Such a limitation has prompted a great interest in the design of carnosine derivatives, which maintaining (or improving) the reactivity with RCS, are more resistant to carnosinase. The present paper intends to critically review the most recent studies oriented to obtaining carnosine derivatives, optimized in terms of reactivity with RCS, selectivity (no reaction with physiological aldehydes) and the pharmacokinetic profile (mainly through an enhanced resistance to carnosinase hydrolysis). The review also includes a brief description of AGEs and ALEs as drug targets and the evidence so far reported regarding the ability of carnosine as inhibitor of AGEs and ALEs formation and the proposed reaction mechanisms.

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Improved Functional Recovery of Ischemic Rat Hearts due to Singlet Oxygen Scavengers Histidine and Carnosine

Cited by 82 publications

References 0 publications

Role of Aldose Reductase in the Metabolism and Detoxification of Carnosine-Acrolein Conjugates

Role of Aldose Reductase in the Metabolism and Detoxification of Carnosine-Acrolein Conjugates

Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial

Transforming dietary peptides in promising lead compounds: the case of bioavailable carnosine analogs

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