Galangin ameliorates cisplatin induced nephrotoxicity in vivo by modulation of oxidative stress, apoptosis and inflammation through interplay of MAPK signaling cascade

Background and purposeCisplatin is a widely used chemotherapeutic agent but now-a-days its usage is limited in clinical chemotherapy because of its severe nephrotoxic effect on renal tissues. Galangin, a flavonoid obtained from ginger family has been demonstrated to have antioxidant, anti-apoptotic and anti-inflammatory properties. This study is aimed to investigate the possible ameliorative effect of galangin in a rodent model of cisplatin-induced nephrotoxicity.Material and methodsAdult male albino wistar rats were divided into six groups (n = 6) viz normal, cisplatin-control, galangin (25, 50 and 100 mg/kg p.o.) and per se (100 mg/kg galangin, p.o.). Galangin was administrated orally to the rats for a period of 10 days. On the 7th day of the treatment, nephrotoxicity was induced in all the groups by a single dose of cisplatin (8 mg/kg, i.p.) (except normal and per se group). On the 11th day, the rats were anaesthetized and blood was withdrawn via direct heart puncture for biochemical estimation. Rats were sacrificed and kidneys were isolated and preserved for evaluation of histopathological, ultra structural immunohistochemical studies and western blot analysis.ResultsCisplatin significantly impaired renal function and increased oxidative stress and inflammation. It also increased expression of pro-apoptotic proteins Bax and caspase-3 and decreased the expression of the anti-apoptotic protein Bcl-2. Histological and ultrastructural findings were also supportive of renal tubular damage. Pretreatment with galangin (100 mg/kg p.o.) preserved renal function, morphology, suppressed oxidative stress, inflammation and the activation of apoptotic pathways. TUNEL assay showed decreased DNA fragmentation on galangin pre-treatment. Furthermore, galangin (100 mg/kg) pre-treatment also reduced the expression of NFκB along with proteins MAPK pathway i.e. p38, JNK and ERK1/2.ConclusionIn conclusion, Galangin (100 mg/kg, p.o.) significantly ameliorated cisplatin induced nephrotoxicity by suppressing MAPK induced inflammation and apoptosis.

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