Transport and distribution of 45Ca2+ in the perfused rat liver and the influence of adjuvant-induced arthritis

Abstract

The purpose of the present work was to investigate Ca(2+) transport and distribution under the conditions of the intact rat liver in health and disease (adjuvant-induced arthritis). The multiple-indicator dilution technique was used with the simultaneous injection of (45)Ca(2+) and indicators into the portal vein under defined conditions and analysis of the outflow profiles by means of a space-distributed variable transit time model. The best description of the (45)Ca(2+) outflow profiles corresponds to a model that assumes rapid distribution of (45)Ca(2+) between the vascular space and the cell surface and a slower transfer into the hepatocytes. In kinetic terms two distinct cellular pools were distinguishable, the cytosol and the endoplasmic reticulum. The concentration of Ca(2+) in the cytosol was much lower than in the vascular space and in the endoplasmic reticulum. The most prominent modification observed in the livers of arthritic rats was the increased Ca(2+) concentration in the hormone-sensitive cellular pool. Furthermore, reduced rates of Ca(2+) influx and efflux between the hormone-sensitive cellular pool and the cytosolic space were also detected in combination with a significantly reduced expression of the sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA2) protein. All these observations mean that in livers from arthritic rats more time is required to replenish the hormone sensitive Ca(2+) stores.

Merlot grape pomace hydroalcoholic extract improves the oxidative and inflammatory states of rats with adjuvant-induced arthritis

“…It should be stressed, however, that our results apply specifically to the Merlot grape pomace as the composition of the grape pomaces varies considerably among the various cultivars (Ribeiro et al, 2015). On the other hand, it would be of interest to investigate if the grape pomace treatment is equally able to prevent the metabolic modifications that are associated to arthritis which, especially in the liver, lead to modifications in important metabolic pathways such as glycolysis, gluconeogenesis and ureogenesis as well as in the calcium homeostasis (Fedatto-Jr et al, 1999Utsunomiya et al, 2013;Yassuda-Filho et al, 2003).…”

“…Furthermore, as a multisystem disease, rheumatoid arthritis also affects organs such as liver, heart, brain and vascular tissue. The liver of rats with adjuvant-induced arthritis, for example, presents increased rates of oxygen uptake, inhibition of gluconeogenesis and stimulation of glycolysis, alterations in the urea cycle and modifications in calcium homeostasis (Fedatto-Jr et al, 1999Utsunomiya, Scaliante, Bracht, & Ishii-Iwamoto, 2013;Yassuda-Filho et al, 2003). Substantial oxidative stress and molecular damage has also been demonstrated to occur in the plasma, liver, brain and heart of both arthritic patients (Mateen, Moin, Khan, Zafar, & Fatima, 2016) and experimental animals Comar et al, 2013;Schubert et al, 2016;Wendt et al, 2015).…”

Green tea extract improves the oxidative state of the liver and brain in rats with adjuvant-induced arthritis

“…There are also indications that, in the liver, the green tea can contribute to normalize the metabolic functions that are substantially modified by arthritis to the point that it is usual to classify these modifications as a cachectic state. [6][7][8][9][10] For example, green tea normalized the activity of glucose 6-phosphate dehydrogenase in the liver, a key enzyme of an important metabolic route ( pentose monophosphate pathway). Based on this observation, one can expect that the green tea treatment should be equally able to normalize the activity of other enzymes (e.g., glucokinase and glucose 6-phosphatase), a hypothesis to be tested by future work.…”

“…4,5 The liver of rats with adjuvant-induced arthritis, for example, presents increased rates of oxygen uptake, inhibition of gluconeogenesis and stimulation of glycolysis, alterations in the urea cycle and modifications in calcium homeostasis. [6][7][8][9][10] A detailed investigation on the oxidative state of the liver of arthritic animals has been carried out more recently. 11 Substantial modifications have been detected, for example higher levels of ROS, protein carbonyl groups and thiobarbituric acid reactive substances (TBARS) in several subcellular fractions (cytosol, mitochondria and peroxisomes).…”