Dog Antioxidant Supplement Research

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References

The science behind our
antioxidant supplement
Paws de Leon tm.

Green Tea

Leone M, Zhai D, Sareth S, Kitada S, Reed JC, Pellecchia M, Cancer prevention by tea polyphenols is
linked to their direct inhibition of antiapoptotic Bcl-2-family proteins. Cancer Res. 2003 Dec 1;63(23):8118-
21
Palermo CM, Westlake CA, Gasiewicz TA. Epigallocatechin gallate inhibits aryl hydrocarbon receptor gene
transcription through an indirect mechanism involving binding to a 90 kDa heat shock protein.
Biochemistry. 2005 Apr 5;44(13):5041-52.
Suzuki M, Tabuchi M, Ikeda M, Umegaki K, Tomita T. Protective effects of green tea catechins on cerebral
ischemic damage. Med Sci Monit. 2004 Jun;10(6):166-74.
Murase T, Haramizu S, Shimotoyodome A, Nagasawa A, Tokimitsu I. Green tea extract improves
endurance capacity and increases muscle lipid oxidation in mice. Am J Physiol Regul Integr Comp
Physiol. 2005 Mar;288(3):R708-15. Epub 2004 Nov 24.
Mandel S, Youdim MB. Catechin polyphenols: neurodegeneration and neuroprotection in
neurodegenerative diseases. Free Radic Biol Med. 2004 Aug 1;37(3):304-17
Adcocks C, Collin P, Buttle DJ. Catechins from green tea (Camellia sinensis) inhibit bovine and human
cartilage proteoglycan and type II collagen degradation in vitro. J Nutr. 2002 Mar;132(3):341-6.
Haqqi TM, Anthony DD, Gupta S, et al. Prevention of collagen-induced arthritis in mice by a polyphenolic
fraction found in green tea. roc Natl Acad Sci USA. 1999 Apr 13;96(8):4524-9.
Reznichenko L, Amit T, Youdim MB, Mandel S. Green tea polyphenol (-)-epigallocatechin-3-gallate
induces neurorescue of long-term serum-deprived PC12 cells and promotes neurite outgrowth. J
Neurochem. 2005 Jun;93(5):1157-67.
Horie N, Hirabayashi N, Takahashi Y, Miyauchi Y, Taguchi H, Takeishi K. Synergistic effect of green tea
catechins on cell growth and apoptosis induction in gastric carcinoma cells. Biol Pharm Bull. 2005 Apr;28
(4):574-9.
Nakachi K, Matsuyama S, Miyake S, Suganuma M, Imai K. Preventive effects of drinking green tea on
cancer and cardiovascular disease: epidemiological evidence for multiple targeting prevention.
Biofactors. 2000; 13(1-4): 49-54.

Tsuneki H, Ishizuka M, Terasawa M, Wu JB, Sasaoka T, Kimura I. Effect of
green tea on blood glucose levels and serum proteomic patterns in
diabetic (db/db) mice and on glucose metabolism in healthy humans.
BMC Pharmacol. 2004 Aug;4(1):18.
Takahashi H, Nomata K, Mori K, Matsuo M, Miyaguchi T, Noguchi M,
Kanetake H. The preventive effect of green tea on the gap junction
intercellular communication in renal epithelial cells treated with a renal
carcinogen. Anticancer Res. 2004 Nov-Dec;24(6):3757-62.
Nakayama M, Suzuki K, Toda M, Okubo S, Hara Y, Shimamura T. Inhibition
of the infectivity of influenza virus by tea polyphenols. Antiviral Res. 1993
Aug;21(4):289-99.
Swezey RR, Aldridge DE, LeValley SE, Crowell JA, Hara Y, Green CE.
Absorption, tissue distribution and elimination of 4-[(3)h]-epigallocatechin
gallate in beagle dogs. Int J Toxicol. 2003 May-Jun;22(3):187-93.

Turmeric Extract

Cuendet M, Pezzuto JM. The role of cyclooxygenase and lipoxygenase in cancer chemoprevention.
Drug Metabol Drug Interact. 2000;17(1-4):109-57. Review.
Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies.
Anticancer Res. 2003 Jan-Feb;23(1A):363-98. Review.
Srivastava, R. and Srimal R.C. (1985). “Modification of certain inflammation-induced biochemical
changes by curcumin”. Ind. J. Med. Res; 81:215-223.
Srimal R.C. and Shawan, B.N, (1973). “Pharmacology of curcumin, a non-steroidal anti-inflammatory
agent”. J. Clin Pharmacol Ther Toxicol; 24:651-654.
Jian YT, Mai GF, Wang JD, Zhang YL, Luo RC, Fang YX. Preventive and therapeutic effects of NF-
kappaB inhibitor curcumin in rats colitis induced by trinitrobenzene sulfonic acid. World J
Gastroenterol. 2005 Mar 28;11(12):1747-52.
Kapadia GJ, Azuine MA, Tokuda H, Hang E, Mukainaka T, Nishino H, Sridhar R. Inhibitory effect of
herbal remedies on 12-O-tetradecanoylphorbol-13-acetate-promoted Epstein-Barr virus early antigen
activation. Pharmacol Res. 2002 Mar;45(3):213-20.
Tomita M, Holman BJ, Santoro CP, Santoro TJ. Astrocyte production of the chemokine macrophage
inflammatory protein-2 is inhibited by the spice principle curcumin at the level of gene transcription. J
Neuroinflammation. 2005 Feb 25;2(1):8.
Rukkumani R, Aruna K, Varma PS, Rajasekaran KN, Menon VP. Comparative effects of curcumin and
an analog of curcumin on alcohol and PUFA induced oxidative stress. J Pharm Pharm Sci. 2004 Aug
20;7(2):274-83.
Shukla PK, Khanna VK, Khan MY, Srimal RC. Protective effect of curcumin against lead neurotoxicity in
rat. Hum Exp Toxicol. 2003 Dec;22(12):653-8.
Manikandan P, Sumitra M, Aishwarya S, Manohar BM, Lokanadam B, Puvanakrishnan R. Curcumin
modulates free radical quenching in myocardial ischaemia in rats. Int J Biochem Cell Biol. 2004 Oct;
36(10):1967-80.
Chan MM, Adapala NS, Fong D. Curcumin overcomes the inhibitory effect of nitric oxide on
Leishmania. Parasitol Res. 2005 Apr;96(1):49-56. Epub 2005 Mar 17.

Alpha Lipoic Acid

Packer L, Witt EH, Tritschler HJ. alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med.
1995 Aug;19(2):227-50. Review.
Lynch MA. Lipoic acid confers protection against oxidative injury in non-neuronal and neuronal
tissue. Nutr Neurosci. 2001;4(6):419-38. Review.
Kohler HB, Huchzermeyer B, Martin M, De Bruin A, Meier B, Nolte I. TNF-alpha dependent NF-kappa
B activation in cultured canine keratinocytes is partly mediated by reactive oxygen species. Vet
Dermatol. 2001 Jun;12(3):129-37.
Ikeda-Douglas CJ, Zicker SC, Estrada J, Jewell DE, Milgram NW. Prior experience, antioxidants, and
mitochondrial cofactors improve cognitive function in aged beagles. Vet Ther. 2004 Spring;5(1):5-16.

Milgram NW, Head E, Zicker SC, Ikeda-Douglas C, Murphey H,
Muggenberg BA, Siwak CT, Tapp PD, Lowry SR, Cotman CW. Long-
term treatment with antioxidants and a program of behavioral
enrichment reduces age-dependent impairment in discrimination
and reversal learning in beagle dogs. Exp Gerontol. 2004 May;39
(5):753-65.
Schupke H, Hempel R, Peter G, Hermann R, Wessel K, Engel J,
Kronbach T. New metabolic pathways of alpha-lipoic acid. Drug
Metab Dispos. 2001 Jun;29(6):855-62
Sen CK, Packer L. Thiol homeostasis and supplements in physical
exercise.Am J Clin Nutr. 2000 Aug;72(2 Suppl):653S-69S. Review.
Shila S, Kokilavani V, Subathra M, Panneerselvam C. Brain
regional responses in antioxidant system to alpha-lipoic acid in
arsenic intoxicated rat. Toxicology. 2005 May 15;210(1):25-36.

Milk Thistle

Katiyar SK. Silymarin and skin cancer prevention: anti-inflammatory, antioxidant and
immunomodulatory effects (Review).Int J Oncol. 2005 Jan;26(1):169-76. Review.
Kravchenko LV, Morozov SV, Tutel'yan VA. Effects of flavonoids on the resistance of microsomes to
lipid peroxidation in vitro and ex vivo. Bull Exp Biol Med. 2003 Dec;136(6):572-5.
Singh RP, Agarwal R. A cancer chemopreventive agent silibinin, targets mitogenic and survival
signaling in prostate cancer. Mutat Res. 2004 Nov 2;555(1-2):21-32. Review.
Skottova N, Kazdova L, Oliyarnyk O, Vecera R, Sobolova L, Ulrichova J. Phenolics-rich extracts from
Silybum marianum and Prunella vulgaris reduce a high-sucrose diet induced oxidative stress in
hereditary hypertriglyceridemic rats. Pharmacol Res. 2004 Aug;50(2):123-30.
Thelen P, Wuttke W, Jarry H, Grzmil M, Ringert RH. Inhibition of telomerase activity and secretion of
prostate specific antigen by silibinin in prostate cancer cells. J Urol. 2004 May;171(5):1934-8.
Singh RP, Agarwal R. Prostate cancer prevention by silibinin.Curr Cancer Drug Targets. 2004 Feb;4
(1):1-11. Review.
Wilasrusmee C, Kittur S, Shah G, Siddiqui J, Bruch D, Wilasrusmee S, Kittur DS.
Immunostimulatory effect of Silybum Marianum (milk thistle) extract. Med Sci Monit. 2002 Nov;8(11):
BR439-43.
Desplaces A, Choppin J, Vogel G, Trost W. The effects of silymarin on experimental phalloidine
poisoning. Arzneimittelforschung. 1975 Jan;25(1):89-96.
Paulova J, Dvorak M, Kolouch F, Vanova L, Janeckova L. [Verification of the hepatoprotective and
therapeutic effect of silymarin in experimental liver injury with tetrachloromethane in dogs] Vet Med
(Praha). 1990 Oct;35(10):629-35. Czech.
Vogel G, Tuchweber B, Trost W, Mengs U. Protection by silibinin against Amanita phalloides
intoxication in beagles. Toxicol Appl Pharmacol. 1984 May;73(3):355-62.

L-Carnosine

Hipkiss AR, Brownson C. A possible new role for the anti-ageing peptide carnosine.Cell Mol Life Sci.
2000 May;57(5):747-53. Review.
Shao L, Li QH, Tan Z. L-carnosine reduces telomere damage and shortening rate in cultured normal
fibroblasts. Biochem Biophys Res Commun. 2004 Nov 12;324(2):931-6.
Holliday R, McFarland GA. A role for carnosine in cellular maintenance. Biochemistry (Mosc). 2000 Jul;
65(7):843-8.
Hobart LJ, Seibel I, Yeargans GS, Seidler NW. Anti-crosslinking properties of carnosine: significance of
histidine. Life Sci. 2004 Jul 30;75(11):1379-89.
McFarland GA, Holliday R. Further evidence for the rejuvenating effects of the dipeptide L-carnosine on
cultured human diploid fibroblasts. Exp Gerontol. 1999 Jan;34(1):35-45.
Kantha SS, Wada S, Tanaka H, Takeuchi M, Watabe S, Ochi H. Carnosine sustains the retention of cell
morphology in continuous fibroblast culture subjected to nutritional insult. Biochem Biophys Res
Commun. 1996 Jun 14;223(2):278-82.
Fujii T, Takaoka M, Tsuruoka N, Kiso Y, Tanaka T, Matsumura Y. Dietary supplementation of L-
carnosine prevents ischemia/reperfusion-induced renal injury in rats. Biol Pharm Bull. 2005 Feb;28(2):
361-3.
Bharadwaj LA, Davies GF, Xavier IJ, Ovsenek N. l-carnosine and verapamil inhibit hypoxia-induced
expression of hypoxia inducible factor (HIF-1 alpha) in H9c2 cardiomyoblasts.Pharmacol Res. 2002
Mar;45(3):175-81.
Kang KS, Yun JW, Lee YS. Protective effect of L-carnosine against 12-O-tetradecanoylphorbol-13-
acetate- or hydrogen peroxide-induced apoptosis on v-myc transformed rat liver epithelial cells. Cancer
Lett. 2002 Apr 8;178(1):53-62.
Hipkiss AR, Michaelis J, Syrris P. Non-enzymatic glycosylation of the dipeptide L-carnosine, a potential
anti-protein-cross-linking agent. FEBS Lett. 1995 Aug 28;371(1):81-5.

Babizhayev MA, Seguin MC, Gueyne J, Evstigneeva
RP, Ageyeva EA, Zheltukhina GA. L-carnosine
(beta-alanyl-L-histidine) and carcinine (beta-
alanylhistamine) act as natural antioxidants with
hydroxyl-radical-scavenging and lipid-peroxidase
activities. Biochem J. 1994 Dec 1;304 ( Pt 2):509-
16.
Quinn PJ, Boldyrev AA, Formazuyk VE. Carnosine:
its properties, functions and potential therapeutic
applications. Mol Aspects Med. 1992;13(5):379-
444. Review.
Cianciaruso B, Fukuda S, Jones MR, Kopple JD.
Net release or uptake of histidine and carnosine in
kidney of dogs. Am J Physiol. 1985 Jan;248(1 Pt 1):
E51-7.

Ashwagandha

Tohda C, Kuboyama T, Komatsu K. Search for natural products related to regeneration of the neuronal
network. Neurosignals. 2005;14(1-2):34-45
Kuboyama T, Tohda C, Komatsu K. Neuritic regeneration and synaptic reconstruction induced by
withanolide A. Br J Pharmacol. 2005 Apr;144(7):961-71.
Owais M, Sharad KS, Shehbaz A, Saleemuddin M. Antibacterial efficacy of Withania somnifera
(ashwagandha) an indigenous medicinal plant against experimental murine salmonellosis.
Phytomedicine. 2005 Mar;12(3):229-35.
Mohan R, Hammers HJ, Bargagna-Mohan P, Zhan XH, Herbstritt CJ, Ruiz A, Zhang L, Hanson AD,
Conner BP, Rougas J, Pribluda VS. Withaferin A is a potent inhibitor of angiogenesis. Angiogenesis.
2004;7(2):115-22.
Jayaprakasam B, Zhang Y, Seeram NP, Nair MG. Growth inhibition of human tumor cell lines by
withanolides from Withania somnifera leaves. Life Sci. 2003 Nov 21;74(1):125-32.
Gupta SK, Mohanty I, Talwar KK, Dinda A, Joshi S, Bansal P, Saxena A, Arya DS. Cardioprotection from
ischemia and reperfusion injury by Withania somnifera: a hemodynamic, biochemical and
histopathological assessment.Mol Cell Biochem. 2004 May;260(1-2):39-47.
Bhattacharya SK, Satyan KS, Ghosal S. Antioxidant activity of glycowithanolides from Withania somnifera.
Indian J Exp Biol. 1997 Mar;35(3):236-9
Schliebs R, Liebmann A, Bhattacharya SK, Kumar A, Ghosal S, Bigl V. Systemic administration of
defined extracts from Withania somnifera (Indian Ginseng) and Shilajit differentially affects cholinergic
but not glutamatergic and GABAergic markers in rat brain. Neurochem Int. 1997 Feb;30(2):181-90.

Bacopa

Russo A, Izzo AA, Borrelli F, Renis M, Vanella A. Free radical
scavenging capacity and protective effect of Bacopa
monniera L. on DNA damage. Phytother Res. 2003 Sep;17
(8):870-5.
Bhattacharya SK, Bhattacharya A, Kumar A, Ghosal S.
Antioxidant activity of Bacopa monniera in rat frontal cortex,
striatum and hippocampus. Phytother Res. 2000 May;14(3):
174-9.
Russo A, Borrelli F, Campisi A, Acquaviva R, Raciti G,
Vanella A. Nitric oxide-related toxicity in cultured astrocytes:
effect of Bacopa monniera. Life Sci. 2003 Aug 8;73(12):
1517-26.
Rohini G, Sabitha KE, Devi CS. Bacopa monniera Linn.
extract modulates antioxidant and marker enzyme status in
fibrosarcoma bearing rats. Indian J Exp Biol. 2004 Aug;42
(8):776-80.
Kar A, Panda S, Bharti S. Relative efficacy of three
medicinal plant extracts in the alteration of thyroid hormone
concentrations in male mice. J Ethnopharmacol. 2002 Jul;
81(2):281-5.

Miscellaneous

Landis GN, Tower J. Superoxide dismutase evolution and life span regulation. Mech Ageing Dev.
2005 Mar;126(3):365-79. Review.
Agarwal S, Sharma S, Agrawal V, Roy N. Caloric restriction augments ROS defense in S. cerevisiae,
by a Sir2p independent mechanism. Free Radic Res. 2005 Jan;39(1):55-62.
Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf
N, Van Remmen H, Wallace DC, Rabinovitch PS. Extension of murine life span by overexpression of
catalase targeted to mitochondria. Science. 2005 Jun 24;308(5730):1909-11. Epub 2005 May 5.
Levin ED. Extracellular superoxide dismutase (EC-SOD) quenches free radicals and attenuates
age-related cognitive decline: opportunities for novel drug development in aging. Curr Alzheimer
Res. 2005 Apr;2(2):191-6.
Levin ED, Christopher NC, Crapo JD. Memory decline of aging reduced by extracellular superoxide
dismutase overexpression. Behav Genet. 2005 Jul;35(4):447-53.
Borras C, Gambini J, Gomez-Cabrera MC, Sastre J, Pallardo FV, Mann GE, Vina J. 17beta-oestradiol
up-regulates longevity-related, antioxidant enzyme expression via the ERK1 and ERK2[MAPK]
/NFkappaB cascade. Aging Cell. 2005 Jun;4(3):113-8.
Devasagayam TP, Tilak JC, Boloor KK, Sane KS, Ghaskadbi SS, Lele RD. Free radicals and
antioxidants in human health: current status and future prospects. J Assoc Physicians India. 2004
Oct;52:794-804. Review.
Kakarla P, Vadluri G, Reddy Kesireddy S. Response of hepatic antioxidant system to exercise
training in aging female rat. J Exp Zoolog A Comp Exp Biol. 2005 Mar 1;303(3):203-8.
Schuessel K, Schafer S, Bayer TA, Czech C, Pradier L, Muller-Spahn F, Muller WE, Eckert A.
Impaired Cu/Zn-SOD activity contributes to increased oxidative damage in APP transgenic mice.
Neurobiol Dis. 2005 Feb;18(1):89-99.
Gunduz F, Senturk UK, Kuru O, Aktekin B, Aktekin MR. The effect of one year's swimming exercise on
oxidant stress and antioxidant capacity in aged rats. Physiol Res. 2004;53(2):171-6.

Ostrander, E.A. et al. Canine genetics comes of age. Trends Genet 16, 117-124 (March 2000).
Oxygen Free Radicals and Aging http://intelegen.com/nutrients/free_radicals_and_aging_1.htm
The Free Radical Theory of Aging Matures KENNETH B. BECKMAN AND BRUCE N. AMES
Department of Molecular and Cell Biology, University of California, Berkeley, California

http://intl-physrev.physiology.org/cgi/content/full/78/2/547

Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf
N, Van Remmen H, Wallace DC, Rabinovitch PS. Extension of murine life span by overexpression
of catalase targeted to mitochondria. Science. 2005 Jun 24;308(5730):1909-11. Epub 2005 May 5.