Biomedical subjects

Leandro Giavarotti

Publications and source records attributed to Leandro Giavarotti.

4 recordsLinked to original sources

PubMed2003

Effects of gamma-hexachlorocyclohexane and L-3,3',5-triiodothyronine on rat liver cytochrome P4502E1-dependent activity and content in relation to microsomal superoxide radical generation.

Liver microsomal cytochrome P4502E1-dependent p-nitrophenol (PNP) hydroxylation and expression of cytochrome P4502E1 were studied in rats subjected to gamma-hexachlorocyclohexane (HCCH) or L-3,3,5-triiodothyronine (T3) administration as a possible mechanism contributing to superoxide radical (O2.-) generation. HCCH treatment (a single dose of 40 mg/kg body wt) produced a 43% increase in the content of total cytochrome P450, whereas T3 (daily doses of 0.1 mg/kg body wt for two consecutive days) led to a 37% decrease. NADPH-dependent O2.- generation was elevated by HCCH and T3, expressed as either per mg of protein or per nmol of cytochrome P450, with a 135% enhancement in the O2.- production/superoxide dismutase (SOD) activity ratios being observed in both conditions. This was partly due to depression of SOD activity. Concomitantly, the molecular activity of NADPH-cytochrome p450 reductase was enhanced by 90 and 69% by HCCH and T3, respectively. In these conditions, microsomal PNP hydroxylation showed increases of 58 and 45% in HCCH- and T3-treated rats over control values, respectively, with a parallel 31% (HCCH) and 41% (T3) enhancement in the content of cytochrome P4502E1 assessed by western immunoblotting. We conclude that HCCH and T3 enhance the expression and activity of cytochrome P4502E1 and that of NADPH-cytochrome P450 reductase in rat liver, regardless of the changes in total cytochrome P450 content, representing major contributory mechanisms to microsomal NADPH-dependent O2.- generation.

Animals↗

PubMed2002

Enhancement of lindane-induced liver oxidative stress and hepatotoxicity by thyroid hormone is reduced by gadolinium chloride.

The role of Kupffer cells in the hepatocellular injury and oxidative stress induced by lindane (20 mg/kg; 24h) in hyperthyroid rats (daily doses of 0.1 mg L-3,3',5-triiodothyronine (T3)/kg for three consecutive days) was assessed by the simultaneous administration of gadolinium chloride (GdCl3; 2 doses of 10mg/kg on alternate days). Hyperthyroid animals treated with lindane exhibit enhanced liver microsomal superoxide radical (O2.-) production and NADPH cytochrome c reductase activity, with lower levels of cytochrome P450, superoxide dismutase (SOD) and catalase activity, and glutathione (GSH) content over control values. These changes are paralleled by a substantial increase in the lipid peroxidation potential of the liver and in the O2.- generation/ SOD activity ratio, thus evidencing a higher oxidative stress status that correlates with the development of liver injury characterized by neutrophil infiltration and necrosis. Kupffer cell inactivation by GdCl3 suppresses liver injury in lindane/T3-treated rats with normalization of altered oxidative stress-related parameters, excepting the reduction in the content of GSH and in catalase activity. It is concluded that lindane hepatotoxicity in hyperthyroid state, that comprises an enhancement in the oxidative stress status of the liver, is largely dependent on Kupffer cell function, which may involve generation of mediators leading to pro-oxidant and inflammatory processes.

Animals↗

PubMed2002

Liver necrosis induced by acute intraperitoneal ethanol administration in aged rats.

It is generally agreed that the deleterious pathophysiological effects of ethanol are caused, at least partially by an increase in free radical production. However, little attention has been directed to the effects of ethanol upon elderly organisms. Male Wistar rats at ages 3, 6, 12, 18 and 24 months were treated either with a single i.p. dose of 35% ethanol (v/v) at 3 g ethanol/kg body weight or an isovolumetric amount of 0.9% saline solution. We then assessed the plasma levels of transaminases and hepatic levels of oxidative stress-related parameters, followed by liver histological evaluation. The younger rats (3 months old) were not affected by the treatment with ethanol with respect to any of the studied parameters except for a lowering of total hepatic GSH and an increase in hepatic thiobarbituric acid reactants (TBARS) formation, while animals older than 3 months were increasingly more affected by the treatment. Acute ethanol treatment elicited the similar responses to those in the 3 months-old group, plus a decrease in the hepatic and plasma levels of beta-carotene and the plasma level of alpha-tocopherol, as well as an increase in the activity of plasma transaminases. In the 12,18 and 24 months old groups, there was increasing liver necrosis. These findings suggest that liver damage induced by acute ethanol administration in elderly rats may involve a lack of antioxidants.

Aging↗

PubMedDate not supplied

Aging and oxidative stress.

The scientific establishment has been discussing the relationship between aging and oxidative stress for quite some time now. While we are still far from a general agreement about this subject, there is an impressive amount of data collected that can be used to draw a compelling picture of the events that take place during the human aging process and their correlation with the oxidant status of the organism. In this review, we bring forth the results of some key studies that can help to elucidate the aging-oxidative stress puzzle, as well as to explain which are the fundamental events in this interplay and why their causal relationships remain so elusive. We also put forward here data on the systemic oxidative stress status of a group of 503 healthy human subjects. The data consist of the plasma levels of TBARS and of the nutritional antioxidants, alpha-tocopherol, beta-carotene and ascorbic acid, and of the activity of the antioxidant enzymes, Cu, Zn-superoxide dismutase, catalase and glutathione peroxidase, of red blood cells. The data indicate that a moderate situation of oxidative stress gradually develops during human aging.

Aging↗