Chromolaena odorata flavonoids attenuate experimental nephropathy: Involvement of pro-inflammatory genes downregulation

Toxicol Rep. 2020 Oct 8:7:1421-1427. doi: 10.1016/j.toxrep.2020.10.006. eCollection 2020.

Abstract

Nephropathy is a serious complication comorbid with a number of life-threatening diseases such as diabetes. Flavonoids are well known cytoprotective phytochemicals. Here, nephropathy associated with streptozotocin (STZ) treatment in experimental animals was challenged by flavonoids (CoF) isolated from Chromolaena odorata. Experimental animals were divided into control (n = 5), STZ (40 mg/kg b.w. i.p. n = 5) and STZ-CoF (CoF = 30 mg/kg b.w. oral, 60 days, n = 7) groups. Blood urea nitrogen (BUN) and serum creatinine (SC) levels were quantified using ELISA. Kidney function, inflammatory marker, and antioxidant gene expression levels were also evaluated using reverse-transcription and polymerase chain reaction protocols. Histological assessment was also performed using Haematoxylin and Eosin (H&E) staining protocols. CoF improved kidney function by restoring BUN/SC levels to pre-STZ treatment states. KIM-1, TNF-α, and MCP-1 but not TNF-R and IL-10 genes were significantly downregulated in STZ-CoF treated group in comparison with STZ-treated group (p < 0.05). Anti-oxidant genes (GPx-1, CAT) significantly (p < 0.05 vs. control) upregulated in STZ-treatment did not respond to CoF treatment. STZ treatment associated Bowman's space enlargement, thickened basement membrane, and glomerulosclerosis were completely reversed in STZ-CoF group. Finally, CoF has demonstrable anti-nephropathic via downregulation of proinflammatory genes and may represent new management option in clinical nephropathy.

Keywords: AKI, Acute kidney injury; ARE, Antioxidant response element; Anti-oxidant; CAT, Catalase; CRD, Committee of Centre for Research and Development; Chromolaena odorata flavonoids (CoF); CoF, Chromolaena odorata is rich in flavonoids; FLVs, Flavonoids; GPx-1, Glutathioneperoxidase; KIM-1, KidneyInjury Molecule-1; MCP-1, Monocyte chemoattractant protein 1; MKK-3, mitogen-activated protein kinase kinase 3; Nephropathy; Nrf2, Nuclear factor-erythroid 2-related factor 2; OCC, Occludin; Pro-inflammation; QoL, Quality of life; ROS, Reactive oxygen species; SOD, Superoxide dismutase; STZ, Streptozotocin; TNF-α-R, Tumour necrosis alpha receptor; Tight junction.