Cyclosporine augments hepatic regenerative response in rats

Abstract

A number of mechanisms participate in the hepatic injury that occurs during and following liver transplantation. A normal allograft regenerative response is probably essential for a successful transplant outcome. In this study, the effect of cyclosporine, a potent immunosuppressant used routinely after liver transplantation, on the regenerative response of the liver after partial hepatectomy was investigated. Male Wistar rats were pretreated for one week with either cyclosporine or the olive oil vehicle and were subjected to either a two-thirds partial hepatectomy or a sham operation. Animals were sacrificed at various times postoperatively and the remnant livers were weighed to determine the liver weight to body weight ratio, two biochemical measures of a regenerative response (cytosolic ornithine decarboxylase activity and thymidine kinase activity), and the hepatic content of estrogen and androgen receptors, as the content of these receptors has been shown to modulate, at least in part, the subsequent hepatic regenerative response. The preoperative hepatic cytosol content of ornithine decarboxylase, thymidine kinase, and estrogen receptor was significantly greater (P less than 0.05) in rats pretreated with cyclosporine than in those treated with the vehicle alone. A significant increase in ornithine decarboxylase and thymidine kinase activities occurred after partial hepatectomy in both the cyclosporine-pretreated and vehicle-pretreated animals. The absolute levels for each parameter were also greater in the cyclosporine-treated animals than in the vehicle-treated controls at 24 hr after partial hepatectomy (P less than 0.05). The pattern of change in the hepatic cytosolic content of estrogen and androgen receptors in both groups of animals was comparable with those described previously for regenerating liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of cyclosporine on hepatic energy status and on fructose metabolism after portacaval shunt in dog as monitored by phosphorus-31 nuclear magnetic resonance spectroscopy in vivo,

“…Interestingly, despite its recognized potential for intrinsic hepatotoxicity (1-10), CsA has been shown to have "hepatotrophic" effects after partial hepatectomy (11)(12)(13)(14)(15)(16) or a PCS (21). Furthermore, CsA does not appear to either prevent or limit the hepatic regenerative response observed when a small-for-size liver is transplanted into a larger recipient (29) or when a reduced-size liver is used in pediatric recipients (30).…”

“…Hepatic regeneration may be crucial during and immediately after transplantation, when the liver recovers from the injury experienced during the period of ischemic cold preservation and reperfusion. The acute effects of CsA on liver regeneration have been investigated recently by several different groups (11)(12)(13)(14)(15)(16). These studies have shown that CsA may actually enhance the hepatocyte's regenerative response after partial hepatectomy.…”

Effects of tacrolimus on ischemia-reperfusion injury

“…120,121 Comparison of low-dose cyclosporine A (0.06 to 0.6 mg/kg/d) with low-dose tacrolimus (0.01 to 0.06 mg/kg/d) directly infused into the portal vein under partially ischemic conditions showed no difference in hepatotropic properties. 121 However, when greater doses of cyclosporine A (4 mg/kg/d) are compared, significantly greater mitosis is stimulated by high-dose tacrolimus (1 mg/kg/d).…”

FK 506 ameliorates the hepatic injury associated with ischemia and reperfusion in rats

“…Attempts to prevent or to diminish the allograft injury associated with organ harvesting, reperfusion and rejection have already involved the use of several different pharmacological agents. Recently, experimental studies obtained in animals have focused considerable attention on the hepatotrophic activities of cyclosporin A (9)(10)(11)(12)(13)(14) and FK (2,3,15), two potent immunosuppressive agents currently being used after clinical OLT.…”