- Email: [email protected]
The Effect of Rooibos (Aspalathus Linearis) Supplementation On Tert-Butylhydroperoxide-Induced Oxidative Damage in Liver and Kidney of Rats
ANTIOXIDANTS AND NOVEL THERAPEUTICS
SFRBM 2011
S81
Antioxidants and Novel Therapeutics 181 The Effect of Rooibos (Aspalathus Linearis) Supplementation On Tert-ButylhydroperoxideInduced Oxidative Damage in Liver and Kidney of Rats Olawale Razaq Ajuwon1, Emma Katengua-Thamahane2, Jacques van Rooyen2, Oluwafemi Oguntibeju1, and Jeanine Marnewick1 1 2 Oxidative Stress Research Centre, Experimental Antioxidant Research Laboratory, Cape Peninsula University of Technology, South Africa Oxidative stress has been implicated in the aetiology of most chronic diseases. This study investigates a possible protective effect of rooibos on tert-butyl hydroperoxide (t-BHP)-induced oxidative stress in the liver and kidney of Wistar rats. Forty animals (n=10/group) were randomly divided into four groups receiving either water or rooibos (2% w/v) as the only source of drinking fluid for 6 weeks followed by a daily t-BHP (30 µmol/100 g body weight, i.p) or vehicle control injection for 2 weeks. Serum aminotransferases, blood urea nitrogen (BUN), and uric acid as marker of organ damage as well as lipid peroxidation (MDAHPLC), oxygen radical absorbance capacity (ORAC), catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx) were estimated as indices of oxidative stress. Injection of t-BHP induced oxidative stress, evidenced by significant (P<0.05) increase in MDA, elevated levels of ALT, AST, BUN and uric acid in the serum and depletion of ORAC status. Rooibos supplementation significantly decreased MDA level in the liver, returned the ORAC status to a level comparable to the control in the kidney and was effective in reducing the level of the serum enzymes. in the liver, t-BHP exhibited varying effects on the level of antioxidant enzymes, with a significant (P< 0.05) to marginal (P<0.1) reduction of GPx and CAT, respectively while activity of GR was significantly (P<0.05) increased when compared with the controls. the levels of antioxidant enzymes, measured in the kidney, were significantly (P<0.05) decreased by t-BHP injection with the exception of SOD that was significantly (P<0.05) elevated. Rooibos supplementation was able to alleviate the t-BHP-induced changes in the liver and kidney, suggesting that consuming rooibos is capable of protecting against hepato- and nephrotoxicity by modulating oxidative damage.
doi:10.1016/j.freeradbiomed.2011.10.385
182 Ketogenic Diets Enhance Lung Cancer Reponse To Therapy Byan Allen1, Luke Szweda2, John Buatti1, Sudershan Bhatia1, Douglas Spitz1, and Melissa Fath1 1 2 University of Iowa, Oklahoma Medical Research Foundation Ketogenic diets (KD) have a high fat content and force cells to rely more heavily on mitochondrial metabolism for energy production. Cancer cells demonstrate alterations in mitochondrial O2 metabolism that result in increased reactive oxygen species formation resulting in oxidative stress. the current study determined if ketogenic diets were capable of enhancing oxidative stress and inducing chemo-radio-sensitization in lung cancer cells. Mice bearing NCI-H292 lung cancer xenografts were fed KetoCal or standard chow for 2 weeks with concurrent chemotherapy (carboplatin 25 mg/kg IP once a week x 3 doses), ionizing radiation (IR; 12 Gy/6 fractions) or the combination; all treatments were well tolerated. Xenografts treated with KD + IR
S82
demonstrated a tumor growth delay over IR alone (p=0.0011) and xenografts treated with KD + IR + carboplatin demonstrated both a survival advantage and a tumor growth delay over animals treated with carbo + IR (p=0.0386 and P<0.0001 respectively). in addition feeding a ketogenic diet combined with hypo-fractionated IR (12 Gy/2fx) also resulted in a significant tumor growth delay, when compared to irradiated animals fed standard chow (p=0.0403). Finally, dot blot analysis of tumors treated with ketogenic diet + hypo-fractionated IR demonstrated increased levels of immunoreactive 4-hydroxynonenal-modified protein supporting the hypothesis that these treatments induce increases in oxidative stress. the current study demonstrates that ketogenic diets increase oxidative stress, as well as sensitizing lung cancer xenografts to radio-chemo-therapy. Supported by R01CA133114, RSNA RR1020, R21CA139182, and UL1RR024979.
doi:10.1016/j.freeradbiomed.2011.10.386
183 Noise Stress Induced Oxidative Stress, DNA Fragmentation and Changes in Hsp-70 Expression in Rat Lymphoid Tissues and Protective Effect of ‘Triphala’ Srikumar Ramasundaram1, and Muthuvel Arumugam2 1 2 Tamilnadu State AIDS Control Society, Chennai, National Institute of Siddha, Chennai,India , University of Madras, Chennai, India. Noise stress induced oxidative stress has already been known. in the present study we have reported noise stress induced oxidative stress in rat lymphoid tissues namely thymus and spleen. Wistar strain male albino rats were subjected to noisestress of 100 dB for 4 h/d for15 days and the development of noise induced stress was confirmed by estimating plasma cortisol. Noise stress induced oxidative stress was examined by estimating lipid peroxidation, antioxidants superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in thymus and spleen. Besides DNA integrity and Heat Shock Protein 70 mRNA (hsp70) expression in thymus and spleen were also examined. the response to treatment with ‘Triphala’ an antioxidant rich siddha medicine herbal formulation was examined. Triphala was used at a dose of 1 g/kg/b.w for 48 days. Results showed depletion of antioxidant status, enhanced DNA fragmentation and elevated hsp70 mRNA expression in thymus and spleen in response to noise stress. Treatment with Triphala prevented anti oxidant depletion, DNA fragmentation and changes in hsp70 expression. It may be concluded that noise stress can alter antioxidant status, DNA integrity and hsp70 expression in lymphoid tissues and can possibly cause immunotoxicity. Triphala has prophylactic value against noise stress induced oxidative stress. Key Words: Noise stress, Oxidative stress, Lymphoid tissues, DNA fragmentation
doi:10.1016/j.freeradbiomed.2011.10.387
SFRBM 2011
SFRBM 2011
S81
Antioxidants and Novel Therapeutics 181 The Effect of Rooibos (Aspalathus Linearis) Supplementation On Tert-ButylhydroperoxideInduced Oxidative Damage in Liver and Kidney of Rats Olawale Razaq Ajuwon1, Emma Katengua-Thamahane2, Jacques van Rooyen2, Oluwafemi Oguntibeju1, and Jeanine Marnewick1 1 2 Oxidative Stress Research Centre, Experimental Antioxidant Research Laboratory, Cape Peninsula University of Technology, South Africa Oxidative stress has been implicated in the aetiology of most chronic diseases. This study investigates a possible protective effect of rooibos on tert-butyl hydroperoxide (t-BHP)-induced oxidative stress in the liver and kidney of Wistar rats. Forty animals (n=10/group) were randomly divided into four groups receiving either water or rooibos (2% w/v) as the only source of drinking fluid for 6 weeks followed by a daily t-BHP (30 µmol/100 g body weight, i.p) or vehicle control injection for 2 weeks. Serum aminotransferases, blood urea nitrogen (BUN), and uric acid as marker of organ damage as well as lipid peroxidation (MDAHPLC), oxygen radical absorbance capacity (ORAC), catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx) were estimated as indices of oxidative stress. Injection of t-BHP induced oxidative stress, evidenced by significant (P<0.05) increase in MDA, elevated levels of ALT, AST, BUN and uric acid in the serum and depletion of ORAC status. Rooibos supplementation significantly decreased MDA level in the liver, returned the ORAC status to a level comparable to the control in the kidney and was effective in reducing the level of the serum enzymes. in the liver, t-BHP exhibited varying effects on the level of antioxidant enzymes, with a significant (P< 0.05) to marginal (P<0.1) reduction of GPx and CAT, respectively while activity of GR was significantly (P<0.05) increased when compared with the controls. the levels of antioxidant enzymes, measured in the kidney, were significantly (P<0.05) decreased by t-BHP injection with the exception of SOD that was significantly (P<0.05) elevated. Rooibos supplementation was able to alleviate the t-BHP-induced changes in the liver and kidney, suggesting that consuming rooibos is capable of protecting against hepato- and nephrotoxicity by modulating oxidative damage.
doi:10.1016/j.freeradbiomed.2011.10.385
182 Ketogenic Diets Enhance Lung Cancer Reponse To Therapy Byan Allen1, Luke Szweda2, John Buatti1, Sudershan Bhatia1, Douglas Spitz1, and Melissa Fath1 1 2 University of Iowa, Oklahoma Medical Research Foundation Ketogenic diets (KD) have a high fat content and force cells to rely more heavily on mitochondrial metabolism for energy production. Cancer cells demonstrate alterations in mitochondrial O2 metabolism that result in increased reactive oxygen species formation resulting in oxidative stress. the current study determined if ketogenic diets were capable of enhancing oxidative stress and inducing chemo-radio-sensitization in lung cancer cells. Mice bearing NCI-H292 lung cancer xenografts were fed KetoCal or standard chow for 2 weeks with concurrent chemotherapy (carboplatin 25 mg/kg IP once a week x 3 doses), ionizing radiation (IR; 12 Gy/6 fractions) or the combination; all treatments were well tolerated. Xenografts treated with KD + IR
S82
demonstrated a tumor growth delay over IR alone (p=0.0011) and xenografts treated with KD + IR + carboplatin demonstrated both a survival advantage and a tumor growth delay over animals treated with carbo + IR (p=0.0386 and P<0.0001 respectively). in addition feeding a ketogenic diet combined with hypo-fractionated IR (12 Gy/2fx) also resulted in a significant tumor growth delay, when compared to irradiated animals fed standard chow (p=0.0403). Finally, dot blot analysis of tumors treated with ketogenic diet + hypo-fractionated IR demonstrated increased levels of immunoreactive 4-hydroxynonenal-modified protein supporting the hypothesis that these treatments induce increases in oxidative stress. the current study demonstrates that ketogenic diets increase oxidative stress, as well as sensitizing lung cancer xenografts to radio-chemo-therapy. Supported by R01CA133114, RSNA RR1020, R21CA139182, and UL1RR024979.
doi:10.1016/j.freeradbiomed.2011.10.386
183 Noise Stress Induced Oxidative Stress, DNA Fragmentation and Changes in Hsp-70 Expression in Rat Lymphoid Tissues and Protective Effect of ‘Triphala’ Srikumar Ramasundaram1, and Muthuvel Arumugam2 1 2 Tamilnadu State AIDS Control Society, Chennai, National Institute of Siddha, Chennai,India , University of Madras, Chennai, India. Noise stress induced oxidative stress has already been known. in the present study we have reported noise stress induced oxidative stress in rat lymphoid tissues namely thymus and spleen. Wistar strain male albino rats were subjected to noisestress of 100 dB for 4 h/d for15 days and the development of noise induced stress was confirmed by estimating plasma cortisol. Noise stress induced oxidative stress was examined by estimating lipid peroxidation, antioxidants superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in thymus and spleen. Besides DNA integrity and Heat Shock Protein 70 mRNA (hsp70) expression in thymus and spleen were also examined. the response to treatment with ‘Triphala’ an antioxidant rich siddha medicine herbal formulation was examined. Triphala was used at a dose of 1 g/kg/b.w for 48 days. Results showed depletion of antioxidant status, enhanced DNA fragmentation and elevated hsp70 mRNA expression in thymus and spleen in response to noise stress. Treatment with Triphala prevented anti oxidant depletion, DNA fragmentation and changes in hsp70 expression. It may be concluded that noise stress can alter antioxidant status, DNA integrity and hsp70 expression in lymphoid tissues and can possibly cause immunotoxicity. Triphala has prophylactic value against noise stress induced oxidative stress. Key Words: Noise stress, Oxidative stress, Lymphoid tissues, DNA fragmentation
doi:10.1016/j.freeradbiomed.2011.10.387
SFRBM 2011