Anti-apoptotic role of spermine against lead and/or gamma irradiation-induced hepatotoxicity in male rats.

Exposure to either lead (Pb) or γ-irradiation (IR) results in oxidative stress in biological systems. Herein, we explored the potential anti-apoptotic effect of spermine (Spm) against lead and/or γ-irradiation-induced hepatotoxicity in male albino rats. Rats were divided into eight experimental groups of ten rats each: groups including negative control, whole body γ-irradiated (6 Gray (Gy)), lead acetate (PbAct) trihydrate orally administered (75 mg/kg bw ≡ 40 mg/kg bw Pb for 14 consecutive days), and Spm intraperitoneally dosed (10 mg/kg bw for 14 consecutive days) rats and groups subjected to combinations of Pb + IR, Spm + IR, Spm + Pb, and Spm + Pb followed by IR on day 14 (Spm + Pb + IR). A significant decrease in arginase activity as well as mRNA and protein levels of Bcl-2 and p21 was observed in rats intoxicated with Pb and/or γ-irradiation compared to controls, whereas Bax mRNA and protein levels were significantly increased. Also, an increased level of nitric oxide (NO) with a reduced arginase activity was observed in liver tissues of intoxicated rats. Spm co-treatment with lead and/or γ-irradiation attenuated the increase in Bax mRNA and protein expression, while it restored those of Bcl-2 and p21 together with NO levels and arginase activity to control values. Altogether, we suggest that Spm may be useful in combating free radical-induced apoptosis in Pb-intoxicated and/or γ-irradiated rats.