Gadolinium chloride suppresses styrene-induced cytochrome P450s expression in rat liver

Abstract

To assess the effect of gadolinium (Gd) on the expression of several forms of cytochrome P450 (P450s) and antioxidant enzymes, we treated rats with gadolinium chloride (25 mg as Gd/kg body weight) 4 h after styrene (a multiple P450 inducer) treatment (600 mg/kg). Gd treatment significantly suppressed styrene-inducible cytochrome P4502B1 (CYP2B1), CYP2B2, CYP2E1, and CYP3A2 mRNA expressions to 48.6%, 69.8%, 61.1%, and 38.5%, accompanying with the reduction of proteins expression to 1.42%, 31.2%, 21.1% and 21.1%, respectively, compared with styrene alone treatment. Gd suppressed styrene-inducible CYP1A2 expression, but only at the protein level. On the other hand, styrene treatment caused a decrease in reduced form of glutathione (GSH), as well as increases in lipid peroxide and serum ALT and AST activities, suggesting the occurrence of hepatic damage probably due to styrene-induced oxidative stress in rat liver. Post-treatment of Gd attenuated this styrene-caused hepatic damage. Moreover, mRNA expressions of cellular antioxidant enzymes such as catalase, CuZn-superoxide dismutase (CuZnSOD) and glutathione peroxidase (GPX) were hardly changed by styrene and/or Gd treatment. In summary, Gd suppressed styrene-inducible expression of not only CYP2B1 but also several forms of P450 at both the mRNA and protein levels, along with attenuation of styrene-caused liver damage. These findings suggested that Gd is a chemo-preventive agent against hepatic damage caused by xenobiotics requiring biotransformation.

The Preventive Effect of Vitamin C on Styrene-Induced Toxicity in Rat Liver and Kidney

“…The effect of ST on experimental animals was reported by several investigators (7,15,22,23). Hirasawa et al (2007) reported that serum AST and ALT activities were significantly increased in rats treated with ST (22). Elevation of ALT and AST was noted in workers exposed to ST (24,25).…”

“…We found that ST induced dose-dependent elevations of ALT, AST, and alkaline phophatase in rat liver. The effect of ST on experimental animals was reported by several investigators (7,15,22,23). Hirasawa et al (2007) reported that serum AST and ALT activities were significantly increased in rats treated with ST (22).…”

Gadolinium Chloride Rescues Niemann–Pick Type C Liver Damage

“…To our knowledge, there are few reports showing protective effects of GdCl 3 treatments in isolated hepatocytes. It was shown that Gd 3+ can reduce the levels of cytochrome P450 in hepatocytes [ 52 ], which in turn can reduce oxidative damage. Oxidative damage is an important feature in NPC; therefore, Gd 3+ can contribute to the beneficial effects observed in vivo.…”

Gadolinium Chloride Restores the Function of the Gap Junctional Intercellular Communication between Hepatocytes in a Liver Injury

“…For example, Harstad and Klaassen suggest that GdCl 3 may increase hepatic metallothionein, and thus protect the liver from cadmium-induced liver injury [28]. Moreover, Hirasawa et al demonstrate that GdCl 3 can penetrate into hepatocytes and protect isolated hepatocytes in vitro by affecting cytochrome P450 [29]. Interestingly, GdCl 3 has been shown to affect the function of gap junction hemi-channels in Xenopus laevis (African Claw Frog) oocytes as a chloride-channel blocker [30].…”