Efeito dos carotenóides licopeno e astaxantina sobre danos renais induzidos por cloreto de mercúrio

Abstract

Mercury is a heavy metal toxic for any living tissue, being kidneys the first target for the inorganic form. Oxidative stress has been pointed as an important molecular mechanism for kidney injury in inorganic mercury poisoning and the interaction of the metal with endogenous thiol-containing molecules, such as δ-aminolevulinate desidratase (δ-ALA-D), seems to contribute to this process. Lycopene and astaxanthin are plentiful carotenoids in tomatoes and algaes and seafoods, respectively. They have been widely studied because of their large antioxidant properties. This work evaluated the ability of lycopene and astaxanthin to prevent HgCl2 toxicity, assessing parameters like δ-ALA-D and glutathione S-transferase (GST) activities, non-protein sulfhydrylic groups content (NPSH), production of thiobarbituric acid reactive substances (TBARS) and activities of antioxidant enzymes like superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), besides creatinine and uric acid plasma levels and histopathological analyses. Adult Wistar rats received lycopene or astaxanthin, by gavage, on doses of 0, 10, 25, or 50 mg/kg, six hours prior to the administration of 0 or 5 mg/kg HgCl2, yielding 8 experimental groups. After twelve hours of exposure to HgCl2 animals were killed. HgCl2 inhibited renal δ-ALA-D activity and increased TBARS levels in kidney and creatinine levels in plasma along with renal tubular necrosis. Lycopene prevented HgCl2-induced inhibition of δ-ALA-D activity and increase of lipid peroxidation in kidney, but not the increase in plasma creatinine levels or renal tubular necrosis caused by HgCl2. Although astaxanthin have not prevented HgCl2-induced inhibition of δ-ALA-D and increase in plasma creatinine levels, this carotenoid prevented lipid peroxidation and attenuated renal tubular necrosis caused by HgCl2. GPx and CAT activities were enhanced, while SOD activity was depressed, in mercury-treated rats when compared to control and these effects were prevented by some lycopene doses and by all astaxanthin doses evaluated. Some doses of lycopene negativelly affected antioxidant enzymes activities per se and the mechanism involved in this response has not been elucidated yet. Neither HgCl2 nor carotenoids treatment changed the content of NPSH groups or GST activity in kidney or uric acid levels in plasma. Our results indicate that although lycopene and astaxanthin did not prevent HgCl2-induced creatinine increase in plasma, changes in the activity of antioxidant enzymes might be limited by the use of these car