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

Phytomedicine. 2017 Oct 15:34:154-161. doi: 10.1016/j.phymed.2017.05.007. Epub 2017 Jun 15.

Abstract

Background and purpose: Cisplatin 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 methods: Adult male albino wistar rats were divided into six groups (n=6) viz normal, cisplatin-control, galangin (25, 50 and 100mg/kg p.o.) and per se (100mg/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 (8mg/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 On the 11th day, the rats were anaesthetized and blood was withdrawn via direct heart puncture for biochemical estimation.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.

Results: Cisplatin 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 (100mg/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 (100mg/kg) pre-treatment also reduced the expression of NFκB along with proteins MAPK pathway i.e. p38, JNK and ERK1/2.

Conclusion: In conclusion, Galangin (100mg/kg, p.o.) significantly ameliorated cisplatin induced nephrotoxicity by suppressing MAPK induced inflammation and apoptosis.

Keywords: Cisplatin; Flavonoid; Galangin; MAPK; Nephrotoxicity.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / drug therapy*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antineoplastic Agents / toxicity
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cisplatin / toxicity*
  • DNA Fragmentation / drug effects
  • Flavonoids / pharmacology*
  • Inflammation / drug therapy
  • Kidney / drug effects*
  • MAP Kinase Signaling System / drug effects*
  • Male
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Antioxidants
  • Bax protein, rat
  • Flavonoids
  • NF-kappa B
  • bcl-2-Associated X Protein
  • galangin
  • Casp3 protein, rat
  • Caspase 3
  • Cisplatin