Cadmium generates reactive oxygen- and carbon-centered radical species in rats: Insights from in vivo spin-trapping studies

Abstract

Cadmium (Cd) is a known industrial and environmental pollutant. In the present work, an in vivo spintrapping technique was used in conjunction with electron spin resonance (ESR) spectroscopy to investigate free radical generation in rats following administration of cadmium chloride (CdCl 2 , 40 µmol/kg) and the spin trapping agent α-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN, 1 g/kg). In Cd-treated rats, POBN radical adducts were formed in the liver, were excreted into the bile, and exhibited an ESR spectrum consistent with a carbon-centered radical species probably derived from endogenous lipids. Isotope substitution of dimethyl sulfoxide [(CH 3 ) 2 SO] with 13 C demonstrated methyl radical formation (POBN/* 13 CH 3 ). This adduct indicated the production of hydroxyl radical, which reacted with [( 13 CH 3 ) 2 SO] to form * 13 CH 3 , which then reacted with POBN to form POBN/ * 13 CH 3 . Depletion of hepatic glutathione by diethyl maleate significantly increased free radical production, whereas inactivation of Kupffer cells by gadolinium chloride and chelation of iron by desferal inhibited it. Treatment with the xanthine oxidase inhibitor allopurinol, the catalase inhibitor aminobenzotriazole, or the cytochrome P450 inhibitor 3-amino-1,2,4-triazole had no effect. This is the first study to show Cd generation of reactive oxygen and carbon-centered radical species by involvement of both iron mediation through iron-catalyzed reactions and activation of Kupffer cells, the resident liver macrophages.

Positive effects of Green Tea on hepatic dysfunction, lipid peroxidation and antioxidant defence depletion induced by cadmium

“…The imbalance between antioxidant/oxidant induced by cadmium was also observed by other authors (Eriyamremu et al, 2008), it causes an increase in hydroxyl radicals (Liu et al, 2008;O'Brien and Salacinski, 1998), superoxide anions, nitric oxide and hydrogen peroxide production (Liu et al, 2008;Chen et al, 2008;Hsu et al, 2007). The free radicals attack hepatic cells, leading to hepatic toxicity and dysfunction that are supported by the increase in LDH, GGT, PAL and PAC activities (Jamshidzadeh et al, 2008;Selmanoglu et al, 2008;Zeashan et al, 2008).…”

Liver and Cadmium Toxicity

“…Breakdown products of lipid peroxides may also react with DNA amino bases and proteins. Cd-generated radical adducts can be detected by electron spin resonance (ESR) [72]. The ESR studies provide direct evidence to identify Cd-generated free radicals as O 2…”

Ethanolic leaf extract of Irvingia gabonensis (o’Rorke) Baill protects against nephrotoxocity and hepatotoxicity in cadmium-induced wistar albino rats

“…Other sources of cadmium include; mining at mines, smelting of ores, and its application in making nickel-cadmium batteries (Liao et al 2005). Humans are at a high risk for cadmium as it accumulates in the body tissues and organs such as the liver, lungs, kidneys, bones, and reproductive organs (Thijssen et al 2007, Alvarez et al 2007) leading to dysfunction and oxidative damage in the various tissues as a result of induced oxidative stress through release of reactive oxygen species (ROS) (Liu et al 2008). …”