Pharmacokinetics of Superoxide Dismutase in Rats After Oral Administration

Regnault, C.; Soursac, Mireille; Roch-Arveiller, M; Postaire, E.; Hazebroucq, G.

doi:10.1002/(sici)1099-081x(199603)17:2<165::aid-bdd945>3.3.co;2-e

Cited by 4 publications

(5 citation statements)

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“…Observations from studies have shown that SOD knockout mice accelerate A β plaque deposition [ 126 ], increase tau phosphorylation [ 127 ] and worsen behavioural deficits [ 128 ], all suggesting that SOD plays a pivotal role in human ageing and AD. Unfortunately, it has been found that the SOD molecule is deactivated and does not become bioavailable as it passes through the GI tract once it encounters acids and enzymes [ 129 , 130 ]. As a result, scientists have worked around this problem by having SOD coupled with a protective protein derived from wheat, which can then sustain the gastric acids and be delivered in full form and absorbed into the bloodstream, thus effectively enhancing the body's own primary defence system [ 131 , 132 ].…”

Section: Supporting the Hypothesismentioning

confidence: 99%

Therapeutic potential of astaxanthin and superoxide dismutase in Alzheimer's disease

Balendra¹,

Singh²

2021

Open Biol.

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Oxidative stress, the imbalance of the antioxidant system, results in an accumulation of neurotoxic proteins in Alzheimer's disease (AD). The antioxidant system is composed of exogenous and endogenous antioxidants to maintain homeostasis. Superoxide dismutase (SOD) is an endogenous enzymatic antioxidant that converts superoxide ions to hydrogen peroxide in cells. SOD supplementation in mice prevented cognitive decline in stress-induced cells by reducing lipid peroxidation and maintaining neurogenesis in the hippocampus. Furthermore, SOD decreased expression of BACE1 while reducing plaque burden in the brain. Additionally, Astaxanthin (AST), a potent exogenous carotenoid, scavenges superoxide anion radicals. Mice treated with AST showed slower memory decline and decreased depositions of amyloid-beta (A β ) and tau protein. Currently, the neuroprotective potential of these supplements has only been examined separately in studies. However, a single antioxidant cannot sufficiently resist oxidative damage to the brain, therefore, a combinatory approach is proposed as a relevant therapy for ameliorating pathological changes in AD.

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Section: Supporting the Hypothesismentioning

confidence: 99%

Therapeutic potential of astaxanthin and superoxide dismutase in Alzheimer's disease

Balendra¹,

Singh²

2021

Open Biol.

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“…Possible factors contributing to these discrepancies are the unfavorable pharmacokinetics and the rapid protein half-life of SOD1. Half life of circulating wild type bovine SOD1 in rat blood is about six minutes [14] and depending on the modifications made to the protein, its half life can increase to about six hours [14-16]. Thus, there is significant interest in developing better SOD delivery systems, and many modifications have been made to the SOD protein to improve its pharmacokinetics and delivery including addition of cell penetrating molecules and targeting sequences [17].…”

Section: Introductionmentioning

confidence: 99%

The delivery of superoxide dismutase encapsulated in polyketal microparticles to rat myocardium and protection from myocardial ischemia-reperfusion injury

Seshadri¹,

Sy²,

Brown³

et al. 2010

Biomaterials

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Oxidative stress is increased in the myocardium following infarction and plays a significant role in death of cardiac myocytes, leading to cardiac dysfunction. Levels of the endogenous antioxidant Cu/Zn-superoxide dismutase (SOD1) decrease following myocardial infarction. While SOD1 gene therapy studies show promise, trials with SOD1 protein have had little success due to poor pharmacokinetics and thus new delivery vehicles are needed. In this work, polyketal particles, a recently developed delivery vehicle, were used to make SOD1-encapsulated-microparticles (PKSOD). Our studies with cultured macrophages demonstrated that PKSOD treatment scavenges both intracellular and extracellular superoxide, suggesting efficient delivery of SOD1 protein to the inside of cells. In a rat model of ischemia/reperfusion (IR) injury, injection of PKSOD, and not free SOD1 or empty particles was able to scavenge IR-induced excess superoxide 3 days following infarction. In addition, only PKSOD treatment significantly reduced myocyte apoptosis. Further, PKSOD treatment was able to improve cardiac function as measured by acute changes in fractional shortening from baseline echocardiography, suggesting that sustained delivery of SOD1 is critical during the early phase of cardiac repair. These data demonstrate that delivery of SOD1 with polyketals is superior to free SOD1 protein therapy and may have potential clinical implications.

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“…PROS, which include the superoxide radical anion (O 2 •− ), peroxynitrite, the hydroxyl radical, and hydrogen peroxide, are constantly produced in living organisms and are involved in the initiation and progression of chronic inflammation. Oxidative stress has been shown to play a significant role in many disease states including arthritis, Parkinson’s disease, amyotrophic lateral sclerosis, cancer, and AIDS. – …”

Section: Introductionmentioning

confidence: 99%

“…Cu,Zn-SOD is known to decrease the steady-state concentration of superoxide radicals and could be a suitable candidate drug; it is, however, quickly eliminated from the bloodstream (6 min in rats and 30 min in humans) and poorly adsorbed from and rapidly degraded in the gastrointestinal tract, thereby compromising its delivery. Attempts have been made to improve delivery by protecting the protein (i) with the hydroxyl radical scavengers homocarnosine or anserine, (ii) by covalent modification with polyethylene glycol (PEG) or sodium chondroitin sulfate, and (iii) by encapsulation into liposomes. – Although modification with PEG represents one of the most conventional ways to protect an enzyme from proteolytic attack, excessive covalent modification can compromise activity .…”

Section: Introductionmentioning

confidence: 99%

“…Oxidative stress has been shown to play a significant role in many disease states including arthritis, Parkinson's disease, amyotrophic lateral sclerosis, cancer, and AIDS. [1][2][3][4] Cu,Zn-SOD is known to decrease the steady-state concentration of superoxide radicals and could be a suitable candidate drug; it is, however, quickly eliminated from the bloodstream (6 min in rats and 30 min in humans) 5 and poorly adsorbed from and rapidly degraded in the gastrointestinal tract, 4 thereby compromising its delivery. Attempts have been made to improve delivery by protecting the protein (i) with the hydroxyl radical scavengers homocarnosine or anserine, 6 (ii) by covalent modification with polyethylene glycol (PEG) 7 or sodium chondroitin sulfate, 8 and (iii) by encapsulation into liposomes.…”

Section: Introductionmentioning

confidence: 99%

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Antioxidant Nanoreactor Based on Superoxide Dismutase Encapsulated in Superoxide-Permeable Vesicles

et al. 2008

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We designed and tested an antioxidant nanoreactor based on encapsulation of Cu,Zn superoxide dismutase in amphiphilic copolymer nanovesicles, the membranes of which are oxygen permeable. The nanovesicles, made of poly(2-methyloxazoline)-poly(dimethylsiloxane)-poly(2-methyloxazoline), successfully encapsulated the protein during their self-assembling process, as proved by confocal laser-scanning microscopy and fluorescence-correlation spectroscopy. Electron paramagnetic resonance spectroscopy and circular dichroism analyses showed that no structural changes appeared in the protein molecules once inside the inner space of the nanovesicles. The function of this antioxidant nanoreactor was tested by pulse radiolysis, which demonstrated that superoxide dismutase remains active inside the nanovesicles and detoxifies the superoxide radical in situ. The membrane of our triblock copolymer nanovesicles plays a double role, both to shield the sensitive protein and to selectively let superoxide and dioxygen penetrate to its inner space. This simple and robust hybrid system provides a selective shielding of sensitive enzymes from proteolytic attack and therefore a new direction for developing drug delivery applications.

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Pharmacokinetics of Superoxide Dismutase in Rats After Oral Administration

Cited by 4 publications

References 0 publications

Therapeutic potential of astaxanthin and superoxide dismutase in Alzheimer's disease

Therapeutic potential of astaxanthin and superoxide dismutase in Alzheimer's disease

The delivery of superoxide dismutase encapsulated in polyketal microparticles to rat myocardium and protection from myocardial ischemia-reperfusion injury

Antioxidant Nanoreactor Based on Superoxide Dismutase Encapsulated in Superoxide-Permeable Vesicles

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