Effects of aging on the susceptibility to the toxic effects of cyclosporin A in rats. Changes in liver glutathione and antioxidant enzymes

Palomero, Jesús; Galán, A.I.; Muñoz, Mauricio Pastor; Tuñón, María J.; González‐Gallego, Javier; Jiménez, Rafael

doi:10.1016/s0891-5849(01)00471-3

Cited by 76 publications

(52 citation statements)

References 55 publications

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“…CC14 in rats caused lipid peroxidation. As the oxidative stress in the body increased, the TBARS in the body also increased (18,19). The TBARS decreased if antioxidants such as car nosine and anserine in chicken extract appear in the body (20).…”

Section: Resultsmentioning

confidence: 99%

Effects of Chicken Extract on Antioxidative Status and Liver Protection under Oxidative Stress

Peng

Lin

2004

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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SummaryChicken extract contains carnosine and anserine, both of which possess some antioxidant abilities. The objective of this study was to investigate the protective effects of chicken extract in male Sprague-Dawley (SD) rats under induced oxidative stress. Carbon tetrachloride was used as the oxidative stress inducer. Glutamic-oxalacetatic transaminase (GOT), glutamic-pyruvic transaminase (GPT), total antioxidant status (TAS), thiobarbituric reactive substances (TBARS), iron content, and the activities of antioxidant enzymes were determined. We concluded that under oxidative stress, the intake of chicken extract was helpful in promoting the activities of antioxidant enzymes and in protecting the liver from oxidative damage.

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Section: Resultsmentioning

confidence: 99%

Effects of Chicken Extract on Antioxidative Status and Liver Protection under Oxidative Stress

Peng

Lin

2004

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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“…CsA has been previously shown to enable repeated administration of monoclonal antibody therapy in patients by reducing the HAMA response (Ledermann et al, 1988;Weiden et al, 1994). Notably, the amount of CsA administered in the in vivo experiments in rats was lower, based on several publications (Palomero et al, 2001;Lee et al, 2002), that the doses commonly used in patients for immunosupression, as calculated from commonly used guidelines for conversion of doses between different species (www.fda.gov/Cber/ gdlns/dose.htm). However, whether CsA can inhibit the antibody formation to the IT will be studied in a clinical trial in 2009 in our clinical trials unit.…”

Section: Discussionmentioning

confidence: 99%

Synergistic anti-cancer effects of immunotoxin and cyclosporin in vitro and in vivo

2009

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BACKGROUND: The clinical use of immunotoxins (ITs) has been hampered by hepatotoxicity, and the induction of a strong human-anti-IT response. The human-anti-IT response results in neutralisation of the immunoconjugates, rendering repetitive treatment inefficacious. METHODS: We evaluated the combination of cyclosporin A (CsA) with various Pseudomonas exotoxin A-based ITs in human breast, cervical, and prostate cancer cell lines measured by protein synthesis, cell viability, and TUNEL assay. Furthermore, expression of essential proteins were analysed by western blot. We used cervical cancer model in nude rats to evaluate the anti-metastatic effect of the combination. The anti-immunogenic response by the CsA treatment was investigated in immunocompetent rats. RESULTS: The combination of CsA with ITs caused remarkable synergistic cytotoxicity, in several cancer cell lines, characterised by protein synthesis inhibition, decreased cell viability, and an increased apoptotic index. Furthermore, the combination strongly inhibited formation of metastases in a cervical cancer model in nude rats with a statistically significant increase in median survival time of the combination-treated animals, as compared with those receiving a suboptimal dose of IT alone. Notably, we found in immunocompetent rats that the anti-IT immunoresponse elicited by repeated administration of IT was efficiently abrogated by CsA; notably the antibody responds towards the highly immunogenic PE was shown to be prevented. CONCLUSION: The combination of ITs and CsA might constitute a significant improvement in the clinical potential of systemic IT treatment of cancer patients.

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“…However, results are contingent on the species or specific tissues assayed and in many cases this relationship has not been found (Palomero et al 2001). This lack of consensus has led some to conclude that progressive accrual of oxidative damage is not an integral component of organismal aging, but rather that species-specific steady state levels of oxidative damage are important determinants of aging (Rikans and Hornbrook 1997).…”

Section: Do Levels Of Oxidative Damage Correlate With Mls?mentioning

confidence: 99%

The oxidative stress theory of aging: embattled or invincible? Insights from non-traditional model organisms

Buffenstein

Edrey

Yang

et al. 2008

AGE

161

131

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Reactive oxygen species (ROS), inevitable byproducts of aerobic metabolism, are known to cause oxidative damage to cells and molecules. This, in turn, is widely accepted as a pivotal determinant of both lifespan and health span. While studies in a wide range of species support the role of ROS in many agerelated diseases, its role in aging per se is questioned. Comparative data from a wide range of endotherms offer equivocal support for this theory, with many exceptions and inconclusive findings as to whether or not oxidative stress is either a correlate or a determinant of maximum species lifespan. Available data do not support the premise that metabolic rate and in vivo ROS production are determinants of lifespan, or that superior antioxidant defense contributes to species longevity. Rather, published studies often show either a negative associate or lack of correlation with species longevity. Furthermore, many long-living species such as birds, bats and mole-rats exhibit high levels of oxidative damage even at young ages. Similarly genetic manipulations altering expression of key antioxidants do not necessarily show an impact on lifespan, even though oxidative damage levels may be affected. While it is possible that these multiple exceptions to straightforward predictions of the free radical theory of aging all reflect speciesspecific, "private" mechanisms of aging, the preponderance of contrary data nevertheless present a challenge to this august theory. Therefore, contrary to accepted dogma, the role of oxidative stress as a determinant of longevity is still open to question.

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Effects of aging on the susceptibility to the toxic effects of cyclosporin A in rats. Changes in liver glutathione and antioxidant enzymes

Cited by 76 publications

References 55 publications

Effects of Chicken Extract on Antioxidative Status and Liver Protection under Oxidative Stress

Effects of Chicken Extract on Antioxidative Status and Liver Protection under Oxidative Stress

Synergistic anti-cancer effects of immunotoxin and cyclosporin in vitro and in vivo

The oxidative stress theory of aging: embattled or invincible? Insights from non-traditional model organisms

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