Antioxidant and pro-oxidant effects of oil palm (Elaeis guineensis) leaves extract in experimental diabetic nephropathy: a duration-dependent outcome.
BACKGROUND
Catechins-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).


METHODS
Animal 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.


RESULTS
Oral 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.


CONCLUSIONS
Our 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.
Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur Malaysia. azizan@ummc.edu.my.
Rajavel
R
Varatharajan
Munavvar Zubaid Abdul
MZ
Sattar
Ivy
I
Chung
Mahmood Ameen
MA
Abdulla
Normadiah M
NM
Kassim
Nor Azizan
NA
Abdullah
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D028023:Arecaceae / Q000737:chemistry*; D004249:DNA Damage / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D055442:Metabolome / Q000187:drug effects; D019255:NADPH Oxidases / Q000032:analysis / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000097:blood
D000975:Antioxidants; D010936:Plant Extracts; D053773:Transforming Growth Factor beta1; D000080242:8-Hydroxy-2'-Deoxyguanosine; D019255:NADPH Oxidases; D003849:Deoxyguanosine; D005978:Glutathione