Chemomodulatory effect Melastoma Malabathricum Linn against chemically induced renal carcinogenesis rats via attenuation of inflammation, oxidative stress, and early markers of tumor expansion

Inflammopharmacology. 2016 Oct;24(5):233-251. doi: 10.1007/s10787-016-0276-1. Epub 2016 Sep 14.

Abstract

Melastoma malabathricum Linn (MM) has high valued for its commercial significance. Indian market (northeast) has great demand for the plants, which extended, its use as a traditional home remedy due to its anti-inflammatory effects. In this study, we scrutinize the therapeutic and protective effect of MM against diethylnitrosamine (DEN) and ferric nitrilotriacetate (Fe-NTA)-induced renal carcinogenesis, renal hyperproliferation, and oxidative stress in rats. Liquid chromatography mass spectroscopy (LC-MS) was used for identification of phytoconstituents. Administration of DEN confirmed the initiation the renal carcinogenesis via enhancing the expansion of tumor incidence. Intraperitoneally, administration of Fe-NTA boost the antioxidant enzymes (phase I), viz., superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and phase II, viz., quinone reductase (QR) and glutathione-S-transferase (GST). It also increased the content of renal lipid peroxidation (LPO), hydrogen peroxidase (H2O2) with decrease content in glutathione content (GSH). It also increased the renal biochemical and non-biochemical parameter. It also confirmed the augment the level of thymidine [3H] incorporation into renal DNA, ornithine decarboxylase (ODC) activity and increased the generation of proinflammatory (TNF-α, IL-6 and IL-β) and inflammatory mediator (PGE2). We also analyzed the macroscopic and histologic of renal tissue. In addition, the effect of phytoconstituent of MM extract was evaluated in silico and free radical scavenging activity against the DPPH and ABTS free radicals. LC-MS confirmed the presence of quercetin >gallic acid in MM extract. Renal carcinogenesis rats treated with MM (100, 250, and 500 mg/kg) confirmed the significantly (P < 0.001) protective effect via reduction the antioxidant (phase I and phase II) enzymes, biochemical parameter and restore the proinflammatory and inflammatory mediator at dose dependent manner. MM altered the ODC and thymidine activity in renal DNA. The chemoprotective effect of MM was confirmed via decreased the renal tumor incidence, which was confirmed by the macroscopic and histopathological observation. Consequently, our result suggests that MM is a potent chemoprotective agent and suppresses DEN+ Fe-NTA-induced renal carcinogenesis, inflammatory reaction, and oxidative stress injury in Wister rats.

Keywords: DEN; Fe-NTA; Inflammatory cytokines; Melastoma malabathricum.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / metabolism*
  • Ferric Compounds / toxicity
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / metabolism
  • Kidney Neoplasms / chemically induced
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / metabolism*
  • Male
  • Melastomataceae*
  • Nitrilotriacetic Acid / analogs & derivatives
  • Nitrilotriacetic Acid / toxicity
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Treatment Outcome
  • Tumor Burden / drug effects
  • Tumor Burden / physiology

Substances

  • Antineoplastic Agents, Phytogenic
  • Biomarkers, Tumor
  • Ferric Compounds
  • Inflammation Mediators
  • Plant Extracts
  • Nitrilotriacetic Acid
  • ferric nitrilotriacetate