Abstract
BackgroundCatechins-rich oil palm (Elaeis guineensis) leaves extract (OPLE) is known to have antioxidant activity. Several polyphenolic compounds reported as antioxidants such as quercetin, catechins and gallic acid have been highlighted to have pro-oxidant activity at high doses. Therefore, the present study was conducted to investigate the antioxidant and pro-oxidant effects of chronically administering high dose of OPLE (1000 mg kg-1) in an animal model of diabetic nephropathy (DN).MethodsAnimal body weight, indexes of glycaemia, renal function and morphology were assessed in diabetic animals with and without OPLE (1000 mg kg-1) for 4 and 12 weeks respectively. Oxidative stress was quantified by measuring levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG), lipid peroxides (LPO) and reduced glutathione (GSH). Transforming growth factor-beta1 (TGF-β1), a key mediator of extracellular matrix accumulation, was analysed in plasma. The mechanisms of OPLE action were evaluated by assessing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits (p22phox and p67phox) expression.ResultsOral administration with high dose of catechins-rich OPLE (1000 mg kg-1) to STZ-induced diabetic rats for 4 weeks attenuated renal dysfunction (hyperfiltration, proteinuria) and development of glomerulosclerosis and tubulointerstitial fibrosis, features that are associated with DN. Suppression of increases in oxidative stress markers (8-OHdG, LPO) and the fibrotic cytokine, TGF-β1 was observed. OPLE also reduced renal expression of NADPH oxidase subunits p22phox and p67phox. In contrast and surprisingly, identical dose of OPLE when administered to diabetic animals for 12 weeks caused worsening of renal dysfunction, histopathology in addition to further elevation of oxidative stress marker (LPO) and TGF-β1. These unfavourable effects of prolonged treatment with 1000 mg kg-1 OPLE were accompanied by increase expression of one of the NADPH oxidase subunits, p22phox.ConclusionOur study indicates that chronic administration of 1000 mg kg-1 OPLE exerts both antioxidant and pro-oxidant effects in DN depending on the duration of treatment. The present study also reveals that the antioxidant/pro-oxidant effects of OPLE are in part, due to modulation of NADPH activity.
Highlights
Catechins-rich oil palm (Elaeis guineensis) leaves extract (OPLE) is known to have antioxidant activity
Experimental and clinical evidence indicates that oxidative stress may contribute to the initiation and development of diabetic nephropathy (DN) [1,2,3,4] and in support, previous study in our laboratory provided evidence for in vivo oxidative stress in kidney of diabetic rats that was accompanied by renal dysfunction such as glomerular hyperfiltration and proteinuria; and structural damage that included glomerulosclerosis and tubulointerstitial fibrosis [5]
Diabetic rats treated with 1000 mg kg−1 OPLE did not show any significant changes in mean body weight and kidney to body weight ratio for both the 4-week and 12-week experimental studies
Summary
Catechins-rich oil palm (Elaeis guineensis) leaves extract (OPLE) is known to have antioxidant activity. Chronic hyperglycaemia can activate multiple pathways that lead to increased generation of O2- and other ROS; some of these pathways include enhanced activity of the mitochondrial electron transport chain [2], increased expression and uncoupling of endothelial nitric oxide synthase [6] and activation of the reduced forms of nicotinamide adenine dinucleotide phosphate (NADPH) [7,8] The latter system is present abundantly in the renal vessels and in the glomerular mesangial and podocyte cells, the macula densa, and the thick ascending limb, distal tubule, and collecting ducts [7]. The renal expression of NADPH oxidase has been shown to be enhanced in an animal model of DN [9]
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