Regenerative activity and liver function following partial hepatectomy in the rat using 31P-MR spectroscopy

Abstract

The aim of the present study was to determine whether alterations in hepatic energy expenditure following partial hepatectomy (PHx), as documented by in vivo hepatic 31 P-MRS, correlate with standard parameters of hepatic regeneration and/or liver function. In addition, we sought to determine whether changes in hepatic energy levels are proportional to the extent of hepatic resection. Adult male Sprague-Dawley rats (4-7 per group) underwent a 40%, 70%, or 90% PHx or sham surgeries. Magnetic resonance spectroscopy (MRS) examinations were performed on each animal 24 or 48 hours thereafter. After MRS examinations, [ 3 H]thymidine incorporation into hepatic DNA, proliferating cell nuclear antigen (PCNA) protein expression, and serum bilirubin determinations were performed on each rat. Twenty-four hours following surgery, rats that had undergone 70% PHx had unchanged adenosine triphosphate (ATP) levels but significantly lower ATP/inorganic phosphate (Pi) ratios (P < .05), whereas, at 48 hours post-PHx, both ATP and ATP/Pi levels were lower than in sham-and nonoperated controls (P < .05). Hepatic regeneration and liver dysfunction mirrored these changes; correlations existed between ATP/Pi ratios and [ 3 H]thymidine incorporation (r ‫؍‬ ؊0.61, P < .005), PCNA protein expression (r ‫؍‬ ؊0.62, P < .005), and serum bilirubin (r ‫؍‬ ؊0.49, P < .05). For rats that had undergone graded resections, depleted energy levels 48 hours post-PHx were proportional to the extent of resection, degree of enhanced regenerative activity, and liver dysfunction. In conclusion, 31 P-MRS-generated ATP/Pi index is a noninvasive, robust determination that correlates with standard parameters of hepatic regeneration and function. (HEPATOLOGY 2002;36:345-353.)

Biochemical metabolic changes assessed by31P magnetic resonance spectroscopy after radiation-induced hepatic injury in rabbits

“…Some previous studies have reported that an increase in PME levels is accompanied by a decrease in PDE levels or increased ratios of hepatic PME/ATP and PME/PDE in acute and chronic diffuse liver diseases [1,2,21,22] . However, in other investigators, and our study, PME levels did not increase nor did PDE levels decrease in the same acute and chronic diffuse liver diseases [6,8] . The main reason for these conflicting findings may be the broad, overlapping characteristics of these peaks along with the multiple signals contributing to these resonances hindering accurate quantification of the PME and PDE peaks [8] .…”

“…However, in other investigators, and our study, PME levels did not increase nor did PDE levels decrease in the same acute and chronic diffuse liver diseases [6,8] . The main reason for these conflicting findings may be the broad, overlapping characteristics of these peaks along with the multiple signals contributing to these resonances hindering accurate quantification of the PME and PDE peaks [8] . Another explanation is that hepatic phospholipid membrane activity may differ in animal models of liver diseases versus liver diseases in humans [6] .…”

“…Already, it has been reported that phosphorus-31 magnetic resonance spectroscopy ( 31 P MRS) not only complements liver biopsy but also is a possible replacement and, furthermore, 31 P MRS has a particular value in assessing disease progression [1] . 31 P MRS has been used to study liver metabolism in vivo for several years, including clinical liver disease ]1 -5] and experimental studies [6][7][8] . It enables the observation o f e n e r g y m e t a b o l i s m t h r o u g h t h e s i g n a l s o f phosphomonoesters (PME), phosphodiesters (PDE), inorganic phosphate (Pi) and adenosine triphosphate (ATP).…”

Noninvasive evaluation of liver repopulation by transplanted hepatocytes using 31P MRS imaging in mice

“…5,6,[8][9][10][11] 31 P MRSI has been used extensively to monitor the energetic status of the liver by monitoring signal from phosphorylated metabolites in rodents and humans. 25,26 CK has been used to monitor in vivo liver-directed gene therapy. 27 However, this is the first demonstration of successful application of this approach for evaluating hepatocyte engraftment and repopulation.…”

Regeneração hepática em bagre africano (Clarias gariepinus) após hepatectomia parcial.

“…O tempo de regeneração em mamíferos depende da espécie e varia conforme os autores. Assim, em ratos, após hepatectomia de 70% o fígado pode regenerar-se entre sete a dez dias (Wunder, 1976;Larsen, 1978;Sanz, 1982Sanz, , 1985Mangnall et al, 2003), sete dias segundo Corbin (2002) e seis a oito dias para Michalopolus (1990). A truta arco-íris regenera o fígado no prazo de 30 dias após HP de 25% e de 36%, sendo inclusive incapaz de manter constante no sangue os níveis de proteína, colesterol e de lipídio (Sanz et al, 1985).…”