title: Kolaviron, a biflavonoid complex of Garcinia kola seeds modulates apoptosis by suppressing oxidative stress and inflammation in diabetes-induced nephrotoxic rats.
abstract: Diabetic nephropathy is a complex disease that involves increased production of free radicals which is a strong stimulus for the release of pro-inflammatory factors. We evaluated the renal protective effect of kolaviron (KV) - a Garcinia kola seed extract containing a mixture of 5 flavonoids, in diabetes-induced nephrotoxic rats. Male Wistar rats were divided into 4 groups: untreated controls (C); normal rats treated with kolaviron (C+KV); untreated diabetic rats (D); kolaviron treated diabetic rats (D+KV). A single intraperitoneal injection of streptozotocin (STZ, 50mg/kg) was used for the induction of diabetes. Renal function parameters were estimated in a clinical chemistry analyzer. Markers of oxidative stress in the kidney homogenate were analyzed in a Multiskan Spectrum plate reader and Bio-plex Promagnetic bead-based assays was used for the analysis of inflammatory markers. The effect of kolaviron on diabetes-induced apoptosis was assessed by TUNEL assay. In the diabetic rats, alterations in antioxidant defenses such as an increase in lipid peroxidation, glutathione peroxidase (GPX) activity and a decrease in catalase (CAT) activity, glutathione (GSH) levels and oxygen radical absorbance capacity (ORAC) were observed. There was no difference in superoxide dismutase (SOD) activity. Diabetes induction increased apoptotic cell death and the levels of interleukin (IL)-1β and tumor necrosis factor (TNF)-α with no effect on IL-10. Kolaviron treatment of diabetic rats restored the activities of antioxidant enzymes, reduced lipid peroxidation and increased ORAC and GSH concentration in renal tissues. Kolaviron treatment of diabetic rats also suppressed renal IL-1β. The beneficial effects of kolaviron on diabetes-induced kidney injury may be due to its inhibitory action on oxidative stress, IL-1β production and apoptosis.
authors.affiliation: Nutrition and Chronic Disease Research Unit, Oxidative Stress Research Centre, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Bellville, South Africa.
authors.forename: Omolola R
authors.initials: OR
authors.lastname: Ayepola
authors.affiliation: Diabetes Discovery Platform, Medical Research Council, Tygerberg, South Africa.
authors.forename: Marlon E
authors.initials: ME
authors.lastname: Cerf
authors.affiliation: Department of Wellness Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Brooks
authors.affiliation: Nutrition and Chronic Disease Research Unit, Oxidative Stress Research Centre, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Bellville, South Africa. Electronic address: oguntibejuo@cput.ac.za.
authors.forename: Oluwafemi O
authors.initials: OO
authors.lastname: Oguntibeju
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D044946:Biflavonoids / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D005419:Flavonoids / Q000494:pharmacology*; D029763:Garcinia kola / Q000737:chemistry; D007249:Inflammation / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007677:Kidney Function Tests; D015227:Lipid Peroxidation; D008297:Male; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D017208:Rats, Wistar; D012639:Seeds / Q000737:chemistry
chemical_list: D000975:Antioxidants; D044946:Biflavonoids; D005419:Flavonoids; D053583:Interleukin-1beta; D010936:Plant Extracts; C045492:kolaviron
keywords: Antioxidant; Cell death; Cytokine; Garcinia kola; Nephrotoxicity