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In Vivo Assessment of Antioxidant Potential of Cerium Oxide Nanoparticles during Hypobaric Hypoxia in Rattus Norvegicus
Antioxidants and Novel Therapeutics 233 Effects of Oral Administration of Plumbago Zeylenica on Reproductive Indices in Male Wistar Rats 1
Rahmat Adetutu Adisa , Hamdalat Folake Adesina2, Oluwasanmi Olayinka Aina2, and Olufunso Olabode Olorunsogo2 1 2 University of Lagos, Nigeria, University of Ibadan, Nigeria Plumbago zeylenica (PZ) contains plumbagin- a naphthoquine reported to be a potent chemotherapeutic agent against breast and prostate cancer. In folklore medicine PZ is usually used as a treatment regimen for malaria and these cancers, however, there is paucity of information on the toxicity of PZ especially to the male reproductive organs. Therefore, the present study evaluates spermato-, hepato-, and testicular toxicity of methanolic extracts of PZ (MEPZ). MEPZ at 50, 100, 150 and 200 mg/kg body weight was orally administered to male Wistar strain albino rats weighing 120 -180g (n = 5) for 7 days. Oral administration of MEPZ (50 – 200 mg/kg body weight) to rats did not have any significant (p > 0.05) effects on the alanine and aspartate amino transferases activities in the plasma. However, there was a significant increase (p<0.05) in the activity of alkaline phosphatase (ALP) in plasma of animals administered 150 and 200 mg/kg of MEPZ. Similarly, significant increases were observed in packed cell volume, haemoglobin concentration, red blood count, and white blood cell count at high doses. There were significant reductions in the sperm count and motility of all MEPZ-treated animals. The viability and the number of morphologically disordered sperms were not statistically different from control. The testicular cytoarchitecture showed no visible lesions except at 150 and 200mg/kg doses where even the germinal epithelia were intact and similar to the controls. These findings suggests that MEPZ might be harmful at high doses of 150 – 200mg/kg as evident in the activity of ALP, sperm quantity, quality and testicular degeneration which may be the mechanism of its action as anticancer agent in chemotherapy of prostate cancer in folklore medicine.
doi:10.1016/j.freeradbiomed.2012.10.239
234 Protective Effects of Rooibos (Aspalathus Linearis) and/or Red Palm Oil (Elaeis Guineensis) Supplementation on Tert-Butyl HydroperoxideInduced Oxidative Hepatotoxicity in Wistar Rats 1
Olawale Razaq Ajuwon , Emma Katengua-Thamahane1, Jacques Van Rooyen1, Oluwafemi Oguntibeju1, and Jeanine Marnewick1 1 Cape Peninsula University of Technology, South Africa The possible protective effects of antioxidant-rich aqueous rooibos extract (Aspalathus linearis), red palm oil (RPO) (Elaeis guineensis) and/or their combination on tert-butyl hydroperoxide (t-BHP)-induced oxidative hepatotoxicity in Wistar rats was investigated. Male Wistar rats, (n=10/group) were randomly divided into eight groups receiving either standard rat pellet (SRP) or SRP and RPO (7 g/kg diet) and having access to either water or aqueous rooibos extract as the source of drinking fluid for 6 weeks, followed by daily t-BHP (30 μmol/100 g body weight, i.p.) or vehicle control injection for two weeks. t-BHP caused an elevation in serum marker enzymes (ALT, AST and LDH), conjugated dienes (CD) and malondialdehyde (MDA) levels, paralleled with significant decrease in glutathione (GSH) and GSH:GSSG status, and inducing various changes in activities of
S102
catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) in the blood and liver. Supplementation with rooibos, RPO and/or their combination, significantly decreased serum level of ALT, AST and LDH as well as liver level of CD and MDA. Likewise the changes observed in the activities of CAT, SOD, GPx and GR, as well as impairment in redox status in the erythrocyte and liver were reversed by supplementation with rooibos, RPO and/or their combination. Though we observed protective effects when rooibos and RPO were supplemented concomitantly in t-BHP treated rats, the observed effects were neither additive nor synergistic. Our data suggested that rooibos and RPO either given alone or combined, are capable of alleviating t-BHPinduced oxidative hepatotoxicity and that the mechanism of this protection may involve inhibition of lipid peroxidation and modulation of antioxidants enzymes and redox status.
doi:10.1016/j.freeradbiomed.2012.10.240
235 In Vivo Assessment of Antioxidant Potential of Cerium Oxide Nanoparticles during Hypobaric Hypoxia in Rattus Norvegicus 1
Aditya Arya , Niroj Kumar Sethy1, Mainak Ddas2, and Kalpana Bhargava1 1 2 Defence Institute of Physiology and Allied Sciences, India IIT Kanpur, India Hypobaric hypoxia is known to cause oxidative stress leading to cellular damage by free radicals and altered oxygen homeostasis. Rapid but acute hypoxia significantly affects the normal functioning of a number of vital organs such as brain, lung, liver, heart and as well as causes cellular damage. Cerium oxide is known to have crystal defects which increase on reducing the size to nanoscale. Also, transition between +3 and +4 oxidation state, is known increases its probability to act as good antioxidant which, unlike other antioxidants persists safely in body avoiding the need of repeated doses. The free radical scavenging capacity of cerium nanoparticles or nanoceria has been demonstrated in vitro. Yet, the prophylactic role of these particles against hypobaric hypoxia induced oxidative stress in vivo is unknown. DMTA capped Nanoparticles were synthesized using Fenton’s chemistry and characterized by Particle analyzer, XRD, SEM, and TEM. Further, a dose of 0.5 mg/kg/week cerium oxide nanoparticles in aqueous solution was optimized for administration via intraperitoneal route for 5 weeks. Rats were then exposed to hypobaric hypoxia equivalent to 25,000 feet altitude for six hours in hypobaric hypoxia chambers. Free radicals and lipid peroxidation was analyzed using DCFDA and MDA assays. It was observed that cerium oxide nanoparticles dose prior to hypoxia potentially reduced the level of free radicals and their derivative in lung tissue as compared to the animals housed in normoxia. The immunological response of rats against nanoceria was also evaluated by estimating proinflamatory (Th1 response) and anti-inflamatory (Th2 response) using Enzyme linked immunosorbent assays of various circulating inflammatory cytokines such as IL-6, TNFĮ, IL-1ȕ IL-4, 1L-4 etc. and their concentrations were found significantly less as compared to that of hypoxia. The study, thus demonstrate the potentials of Cerium oxide nanoparticles to protect free radical mediated oxidative stress in rat during hypobaric hypoxia.
doi:10.1016/j.freeradbiomed.2012.10.241
SFRBM 2012
Rahmat Adetutu Adisa , Hamdalat Folake Adesina2, Oluwasanmi Olayinka Aina2, and Olufunso Olabode Olorunsogo2 1 2 University of Lagos, Nigeria, University of Ibadan, Nigeria Plumbago zeylenica (PZ) contains plumbagin- a naphthoquine reported to be a potent chemotherapeutic agent against breast and prostate cancer. In folklore medicine PZ is usually used as a treatment regimen for malaria and these cancers, however, there is paucity of information on the toxicity of PZ especially to the male reproductive organs. Therefore, the present study evaluates spermato-, hepato-, and testicular toxicity of methanolic extracts of PZ (MEPZ). MEPZ at 50, 100, 150 and 200 mg/kg body weight was orally administered to male Wistar strain albino rats weighing 120 -180g (n = 5) for 7 days. Oral administration of MEPZ (50 – 200 mg/kg body weight) to rats did not have any significant (p > 0.05) effects on the alanine and aspartate amino transferases activities in the plasma. However, there was a significant increase (p<0.05) in the activity of alkaline phosphatase (ALP) in plasma of animals administered 150 and 200 mg/kg of MEPZ. Similarly, significant increases were observed in packed cell volume, haemoglobin concentration, red blood count, and white blood cell count at high doses. There were significant reductions in the sperm count and motility of all MEPZ-treated animals. The viability and the number of morphologically disordered sperms were not statistically different from control. The testicular cytoarchitecture showed no visible lesions except at 150 and 200mg/kg doses where even the germinal epithelia were intact and similar to the controls. These findings suggests that MEPZ might be harmful at high doses of 150 – 200mg/kg as evident in the activity of ALP, sperm quantity, quality and testicular degeneration which may be the mechanism of its action as anticancer agent in chemotherapy of prostate cancer in folklore medicine.
doi:10.1016/j.freeradbiomed.2012.10.239
234 Protective Effects of Rooibos (Aspalathus Linearis) and/or Red Palm Oil (Elaeis Guineensis) Supplementation on Tert-Butyl HydroperoxideInduced Oxidative Hepatotoxicity in Wistar Rats 1
Olawale Razaq Ajuwon , Emma Katengua-Thamahane1, Jacques Van Rooyen1, Oluwafemi Oguntibeju1, and Jeanine Marnewick1 1 Cape Peninsula University of Technology, South Africa The possible protective effects of antioxidant-rich aqueous rooibos extract (Aspalathus linearis), red palm oil (RPO) (Elaeis guineensis) and/or their combination on tert-butyl hydroperoxide (t-BHP)-induced oxidative hepatotoxicity in Wistar rats was investigated. Male Wistar rats, (n=10/group) were randomly divided into eight groups receiving either standard rat pellet (SRP) or SRP and RPO (7 g/kg diet) and having access to either water or aqueous rooibos extract as the source of drinking fluid for 6 weeks, followed by daily t-BHP (30 μmol/100 g body weight, i.p.) or vehicle control injection for two weeks. t-BHP caused an elevation in serum marker enzymes (ALT, AST and LDH), conjugated dienes (CD) and malondialdehyde (MDA) levels, paralleled with significant decrease in glutathione (GSH) and GSH:GSSG status, and inducing various changes in activities of
S102
catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) in the blood and liver. Supplementation with rooibos, RPO and/or their combination, significantly decreased serum level of ALT, AST and LDH as well as liver level of CD and MDA. Likewise the changes observed in the activities of CAT, SOD, GPx and GR, as well as impairment in redox status in the erythrocyte and liver were reversed by supplementation with rooibos, RPO and/or their combination. Though we observed protective effects when rooibos and RPO were supplemented concomitantly in t-BHP treated rats, the observed effects were neither additive nor synergistic. Our data suggested that rooibos and RPO either given alone or combined, are capable of alleviating t-BHPinduced oxidative hepatotoxicity and that the mechanism of this protection may involve inhibition of lipid peroxidation and modulation of antioxidants enzymes and redox status.
doi:10.1016/j.freeradbiomed.2012.10.240
235 In Vivo Assessment of Antioxidant Potential of Cerium Oxide Nanoparticles during Hypobaric Hypoxia in Rattus Norvegicus 1
Aditya Arya , Niroj Kumar Sethy1, Mainak Ddas2, and Kalpana Bhargava1 1 2 Defence Institute of Physiology and Allied Sciences, India IIT Kanpur, India Hypobaric hypoxia is known to cause oxidative stress leading to cellular damage by free radicals and altered oxygen homeostasis. Rapid but acute hypoxia significantly affects the normal functioning of a number of vital organs such as brain, lung, liver, heart and as well as causes cellular damage. Cerium oxide is known to have crystal defects which increase on reducing the size to nanoscale. Also, transition between +3 and +4 oxidation state, is known increases its probability to act as good antioxidant which, unlike other antioxidants persists safely in body avoiding the need of repeated doses. The free radical scavenging capacity of cerium nanoparticles or nanoceria has been demonstrated in vitro. Yet, the prophylactic role of these particles against hypobaric hypoxia induced oxidative stress in vivo is unknown. DMTA capped Nanoparticles were synthesized using Fenton’s chemistry and characterized by Particle analyzer, XRD, SEM, and TEM. Further, a dose of 0.5 mg/kg/week cerium oxide nanoparticles in aqueous solution was optimized for administration via intraperitoneal route for 5 weeks. Rats were then exposed to hypobaric hypoxia equivalent to 25,000 feet altitude for six hours in hypobaric hypoxia chambers. Free radicals and lipid peroxidation was analyzed using DCFDA and MDA assays. It was observed that cerium oxide nanoparticles dose prior to hypoxia potentially reduced the level of free radicals and their derivative in lung tissue as compared to the animals housed in normoxia. The immunological response of rats against nanoceria was also evaluated by estimating proinflamatory (Th1 response) and anti-inflamatory (Th2 response) using Enzyme linked immunosorbent assays of various circulating inflammatory cytokines such as IL-6, TNFĮ, IL-1ȕ IL-4, 1L-4 etc. and their concentrations were found significantly less as compared to that of hypoxia. The study, thus demonstrate the potentials of Cerium oxide nanoparticles to protect free radical mediated oxidative stress in rat during hypobaric hypoxia.
doi:10.1016/j.freeradbiomed.2012.10.241
SFRBM 2012