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exposure to low levels of Cd leads to excessive accumulation in certain tissues, especially

lung, liver, kidney and testes (Zitkevicius et al., 2011). The pathophysiology of Cd depends
primarily on the generation of oxidative stress which leads to lipid peroxidation, membrane

protein and DNA damage (Bharavi et al., 2010).
In the recent years a growing interest has been focused on possible ways of protection

from adverse effects of Cd exposure. Although several studies have established numerous
antagonists and chelating agents against Cd-induced toxicity yet these are burdened with

limitations either in terms of safety or efficacy. Currently, flavonoids and other phenolic

compounds are emerging topics due to their protective potential against number of chronic
and degenerative diseases (Prabu et al., 2010). These health-promoting effects of flavonoids

are attributed to their antioxidative, metal chelating and free radical scavenging properties

(Prabu et al., 2011).
Naringenin (4,5,7-trihydroxy flavonone) (NG) is naturally occurring plant flavonone

widely distributed in grapefruits, cherries and tomatoes and predominantly present in citrus
fruits. NG has attracted considerable attention due to its wide range of biological applications

including anti-inflammatory, antiatherogenic, hepatoprotective, anticancer and antimutagenic
with low toxicity (Lee et al., 2004; Inês Amaro et al., 2009). Therefore, the focus of this

review is to highlight the pharmacological properties of NG and its protective effects against

Cd induced toxicity in animals and human beings.
2. MECHANISM OF TOXICITY INDUCED BY CADMIUM

The mechanism of Cd toxicity can be explained by its role in induction of oxidative

stress or by direct displacement of essential metals like zinc and selenium from enzymes at
their binding sites by Cd, thereby inactivating the enzymes (Thévenod, 2010). Although Cd is

not a redox active metal, yet it indirectly contributes to oxidative stress via displacement of
redox-active metals such as iron from intracellular sites (cytoplasmic and membrane proteins)

releasing free iron which produces reactive oxygen species (ROS) through Fenton reactions,

and inhibition of antioxidant enzymes (Nemmiche et al., 2012). As a thiol-affectionate metal,
Cd causes depletion of glutathione (which scavenges intracellular ROS) and protein-binding

sulfhydyl groups resulting in increased production of ROS, which ultimately leads to lipid
peroxidation and ROS mediated DNA.

Mitochondrial dysfunction is also an important aspect of Cd toxicity. Cd binds to
protein thiols on mitochondrial membrane resulting in disrupted mitochondrial membrane

potential, decreased ATP production, uncoupling of oxidative phosphorylation, generation of

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