Title:Nickel and Oxidative Stress: Cell Signaling Mechanisms and Protective Role of Vitamin C
Volume: 20
Issue: 7
Author(s): Swastika Das, Rachamalla C. Reddy, Kailash S. Chadchan, Arun J. Patil, Mallanagouda S. Biradar and Kusal K. Das*
Affiliation:
- Department of Physiology, Laboratory of Vascular Physiology and Medicine, Shri B. M. Patil Medical College, Hospital and Research Centre, BLDE (Deemed to be University), Vijayapur-586103, Karnataka,India
Keywords:
Antioxidant, cyclooxygenase, hypoxia-inducible factor-1α, nickel, oxidative stress, tumor necrosis factor-α.
Abstract:
Background: Nickel activates the signaling pathways through the oxygen sensing mechanism
and the signaling cascades that control hypoxia-inducible transcriptional gene expressions
through oxidative stress. This review emphasizes on the recent updates of nickel toxicities on oxidant
and antioxidant balance, molecular interaction of nickel and its signal transduction through low oxygen
microenvironment in the in-vivo physiological system.
Discussion: Nickel alters intracellular chemical microenvironment by increasing ionized calcium
concentration, lipid peroxidation, cyclooxygenase, constitutive nitric oxide synthase, leukotriene
B4, prostaglandin E2, interleukins, tumor necrosis factor-α, caspases, complement activation, heat
shock protein 70 kDa and hypoxia-inducible factor-1α. The oxidative stress induced by nickel is
responsible for the progression of metastasis. It has been observed that nickel exposure induces the
generation of reactive oxygen species which leads to the increased expression of p53, NF-kβ, AP-1,
and MAPK. Ascorbic acid (vitamin C) prevents lipid peroxidation, oxidation of low-density lipoproteins
and advanced oxidation protein products. The mechanism involves that vitamin C is capable of
reducing ferric iron to ferrous iron in the duodenum, thus the availability of divalent ferrous ion
increases which competes with nickel (a divalent cation itself) and reduces its intestinal absorption
and nickel toxicities.
Conclusion: Reports suggested the capability of ascorbic acid as a regulatory factor to influence gene
expression, apoptosis and other cellular functions of the living system exposed to heavy metals, including
nickel.