Nrf2 transcription factor gene regulates basal transcription of mitochondrial superoxide dismutase enzyme in mouse brain

Evidence suggests that the Nrf2 transcription factor participates in the regulation of expression of genes that contain functional antioxidant responsive elements (AREs) in their promoter regions. Previous studies have shown that induction of glutathione-S- transferases (GST) and NADPH quinone reductase 1 (NQO1) by t-butylated hydroxy anisole (BHA) is impaired in the livers of Nrf2(-/-) mice. Basal expression of certain antioxidant enzymes is also lower in the livers of Nrf2 (-/-) mice. Results indicate that Nrf2 contributes to basal expression but not inducible expression of mitochondrial superoxidedismutase. SOD2 level was affected in the Nrf2(-/-) and about 2-fold lower than the Nrf2(+/+) mouse control. The dietary additives caused a small induction of SOD2 in the Nrf2(-/-) mouse brain, ethoxyquin andkahwoel palmitate each induced SOD2 marginally, while oltipraz and indole-3-carbinol caused 1.5 fold induction in the Nrf2(-/-) mouse brain. In contrast, there was no obvious effect on SOD2 in the Nrf2(+/+) mouse brain by any of the chemicals used

Lipid profile of alloxan-induced diabetic wistar rats treated with methanolic extract of Adansonia digitata fruit pulp

This study was carried out to assess the antidiabetic properties ofAdansoniadigitata fruit pulp by evaluating the effect of its methanolicextract (MAD) on cholesterol, High Density Lipoprotein (HDL), Low DensityLipoprotein (LDL) and triglycerides. Forty eight male wistar/albino ratsweighing 160 to 240 g were randomly distributed into six treatment groups[Group1, Normal control, each given only 0.2 ml distilled water daily for 4weeks; Group 2, diabetes control rats, induced with 150 mg/kg b.w., i.p.administration of alloxan and thereafter given 0.2 ml distilled waterthroughout the study period; Groups 3, 4 and 5, diabetic (i.p., 150 mg/kgb.w. alloxan) rats were given single oral dose of MAD (100, 200 and 300mg/kg b.w. respectively) for 4 weeks; Group 6, diabetic rats (i.p., 150mg/kg b.w. alloxan) were treated with 84 mg/kg b.w. of Chloropropamide,once daily for 4 weeks]. The serum concentration of cholesterol, HDL, LDLand triglycerides of all the animals in each group were determined after the14th and 28th treatment. There was significant (P<0.001) reduction ofserum cholesterol, LDL and Triglycerides when compared with the diabeticcontrol rats. These reductions were dose dependent and compared wellwith values obtained in the standard drug control group. Significant(P<0.001) increase in HDL were seen in the MAD experimental groups butdiffered significantly (P<0.001) with reduction seen in chloropropamidegroup.Keywords: Antidiabetic property, Adansoniadigitata fruit pulp, Lipid profile,Wistar Rat

Regulation of glutathione synthesising and recycling enzymes by xenobiotics in SH-SY5Y neuroblastoma cells

Neurones are prone to oxidative stress and damage due to low levels of endogenous antioxidants (both protein and non protein molecules). Hence, this work looked at the possibility of increasing the levels of antioxidants molecule in neuronal cell line. With such increase, it is thought possible that neuronal cell integrity could be improved in the face of oxidants assault. In this study ethoxyquin and t-BHQ induced gamma glutamyl cysteine ligase enzyme regulatory subunit (GLCR) and caused increase in intracellular glutathione level significantly. The increase of GSH was not accompanied by induction of GS or catalytic subunit of gamma glutamyl cysteine ligase at protein level. Co-administration of selenium as sodium selenite with other inducers of antioxidants further increased the level of intracellular glutathione. This provides a hope that inducers of endogenous antioxidants protein capable of passing blood-brain barrier might attenuate the progression of brain ageing due to genetic diseases associated with increased production of free radical.Keywords: Antioxidant enzymes, GSH, Oxidative stress, Chemopreventive agent

Regulation glutathione synthesizing and regenerating enzymes by xenobiotics in the brain of mice with targeted deletion of the NRF2 transcription factor gene

Basal expression of certain antioxidant enzymes was shown to be lower in the livers of Nrf2(-/-) mice (Hayes et al., 2000). In order to investigate the role of Nrf2 in the regulation of GSH synthesizing and regenerating enzymes in the brain, cytosols from the brains of Nrf2(-/-) mice treated with the antioxidant agents ethoxyquin, oltipraz, kahweol palmitate or indole-3-carbinol were analysed for glutathione content, expression and activity of certain antioxidant enzymes. The analysis enzyme activities indicated reduction of 6 phosphogluconate dehydrogenase and Glutathione reductase activities by almost 14 and 20% in Nrf2 null compared with the wild type control respectively. Treatment with chemopreventive agents increased the levels of these enzymes in Nrf2(-/-) mice brain. But only 6-phosphogluconate dehydrogenase activity was increase in both Nrf2(+/+) and Nrf2(-/-) mice brain. However, deletion of Nrf2 did not affect the protein levels of glutmyl cysteine ligase (GCL) and glutathione synthetase (GS) enzymes. Despite lack of apparent effect of the deficiency of Nrf2 onthe levels of proteins of GCL and GS, upon treatment with chemical additives, there was an increase in the level of GSH in both Nrf2(+/+)and Nrf2(-/-) mice brain upon treatment with chemical additives.Keywords: Antioxidant, Beta zipper (bZip) transcription factors Glutamylcysteine Ligase , Glutamylcysteine Ligase Modifier subunit,  Glutamylcysteine Ligase Catalytic subunit, Glutathione synthetase , Glutathione peroxidise1 Abbreviation: Nrf1, Nrf

Effect of Food Sources of Natural Chemo preventive Agents on Endogenous Antioxidant Enzymes in Brain and Kidney Tissues of Mice

Objective: The work attempted to evaluate the potential of natural products containing cancer chemopreventive agents in increasing the level of some endogenous antioxidant enzymes such as Glutathione STransferase (GST), Glutathione reductase (GR), catalase, superoxide dismutase(SOD-1,2) in brain and kidney tissues of mice. Animals and Methods: Forty eight (48) were separated into six groups. The groups were treated individually with honey, cabbage, green tea and onion as well as the combination of these natural products with exception of control group for three months (twelve weeks) after which all animals were sacrificed. One half was utilized for histological analysis to confirm if chemo-preventive agents had adverse effects on the tissues, while the other half was assessed for endogenous antioxidant enzyme inductions. Results: Histological analysis revealed no damage to brain and kidney tissues. The natural antioxidant preparation increased GR activity by 8%, GST activity by 15% and SOD2 activity by 54% (