Evidence of mitochondrial dysfunction in broilers with pulmonary hypertension syndrome (Ascites): effect of t-butyl hydroperoxide on hepatic mitochondrial function, glutathione, and related thiols

Abstract

The purpose of this study was to assess mitochondrial function and glutathione (a mitochondrial antioxidant) in response to oxidative stress in mitochondria in vitro obtained from broilers with and without pulmonary hypertension syndrome (PHS). Liver mitochondria from Control and PHS broilers were incubated with 0, 1, and 5-mM tertiary-butyl hydroperoxide (tBH). Indices of mitochondrial function [the respiratory control ratio (RCR) and the adenosine diphosphate to oxygen ratio (ADP:O)], and levels of mitochondrial and extra-mitochondrial reduced (GSH) and oxidized (GSSG) glutathione, cysteine, cystine, glutamate and cysteinyl-glycine were determined following tBH treatment. Lower RCR and ADP:O values were observed in PHS mitochondria than in controls. Whereas control mitochondria remained coupled (RCR > 2.0), only 3 PHS preparations remained coupled after 60 min of incubation with 5 mM tBH, indicating a greater susceptibility to oxidative stress in PHS mitochondria. The lower RCR in PHS mitochondria was due to increased oxygen consumption during State IV respiration. Oxidative stress following tBH treatment (decreased GSH and increased GSSG) was observed, but there were no differences in GSH or GSSG between control and PHS mitochondria. The PHS mitochondria did exhibit elevated mitochondrial and extramitochondrial cystine than controls, however. The results indicate that PHS mitochondria do not lack antioxidant protection from GSH, but lower RCR and ADP:O ratios in PHS mitochondria indicate a dysfunction that may contribute to the pathophysiology of this metabolic disease in broilers.

Changes of haematic parameters, redox status and mitochondrial complex activity in the heart and liver of broilers fed with different density diets under low ambient temperature

“…Heart and liver mitochondria were obtained by differential centrifugation procedures as described by Cawthon et al (1999). The activities of the respiratory chain complexes were analysed using a spectrophotometer (Ultrospec 2100 Pro; Biochrom, Berlin, Germany) as described by Hatefi & Stiggall (1978), Iqbal et al (2004 and Liu et al (2007).…”

Mitochondrial Dysfunction Is an Early Manifestation of 1,1-Dichloroethylene-Induced Hepatotoxicity in Mice

“…Inhibition of respiratory parameters was not identified under these conditions. To validate the assay for mitochondrial toxicity in vitro, isolated mitochondria were incubated with tBH, a known mitochondrial toxicant, and this system was used as a positive control (Lash et al, 1995;Cawthon et al, 1999). tBH significantly inhibited state 3 respiration rates and increased state 4 respiration rates, resulting in significantly reduced RCRs.…”

Glutamic acid and protein reduction for broilers and commercial laying hens

“…The glutathione is a tripeptide (glutamic acid, glutamine and glycine) that acts as an antioxidant for the cells protection against the oxidative stress caused by peroxides (CAWTHON et al, 1999;WANG et al, 1997). Therefore, the glutamate performs an important role in the removal of oxidants and in regulation of the antibody response (LI et al, 2007;WU et al, 2004).…”

“…This non essential amino acid is important for the maintenance of the intestinal mucosa, for being source of energy for the mucosa turnover, via the ATP produced from the cycle of Krebs; is source of nitrogen for the synthesis of other amino acids and nitrogen compounds; and glutathione precursor (BERRES et al, 2010). The glutathione is a tripeptide composed by glutamic acid, glutamine and glycine, which acts in the mitochondrial matrix and cytosol as an antioxidant for the cells protection against the oxidative stress caused by peeroxides (CAWTHON et al, 1999;WANG et al, 1997).…”