Spermine increases arginase activity in the liver after carbon tetrachloride-induced hepatic injury in Long-Evans rats.

Arginase is the enzyme which synthesizes urea and ornithine, a precursor from which putrescine, spermidine and spermine are formed. These natural polyamines have been implicated in cell growth, replication and wound healing. The present study evaluated the possibility that spermine increases arginase activity and reduces liver damage caused by carbon tetrachloride. Intraperitoneally injected spermine at a dose of 1 mg/kg after a single intragastric administration of carbon tetrachloride (1.6 ml/kg) increased arginase activity (6.30-7.79 microg urea/mg protein per min) (P<0.05) as well as total protein content (0.29-0.37 mg/mg dry weight) in hepatic tissue, compared to the group which only received carbon tetrachloride. When liver cell damage was biochemically assessed, the carbon tetrachloride-treated group showed a 20-fold increase in serum glutamic oxaloacetate transaminase, compared to the control group (P<0.05), and this was significantly diminished by the administration of spermine (P<0.05). Serum triglycerides increased four times compared to the control group as a result of the carbon tetrachloride treatment and were diminished by spermine as well. These results indicate that spermine may play a role in the recovery of liver tissue after carbon tetrachloride-induced liver injury, maybe by increasing the synthesis of putrescine, a polyamine which has been found out to participate in the recovery of the hepatic tissue after an insult with carbon tetrachloride.

Regeneration of beta-cells and neogenesis from small ducts or acinar cells promote recovery of endocrine pancreatic function in alloxan-treated rats.

BACKGROUND: We previously showed by using biochemical parameters that male Sprague-Dawley rats receiving a single intraperitoneal (i.p.) administration of alloxan (120 mg/kg body weight) with no further treatment recovered endocrine pancreatic function after 12 days. METHODS: Male Sprague-Dawley rats received an i.p. injection of alloxan (120 mg/kg body wt), were killed at 3, 6, 9, or 12 days (n=7), and their capacity to recover endocrine function was evaluated by means of a) biochemical parameters, which included glucose, triglyceride, and total cholesterol measurements and b) nuclear incorporation of 5'-bromodeoxyuridine (BrdU) by beta and acinar cells as well as presence of neogenesis from either ductal or acinar cells using double-staining BrdU-insulin immunohistochemical technique. RESULTS: Three days after receiving a single i.p. administration of alloxan, rats showed increase in serum glucose, triglyceride, and total cholesterol concentrations, reaching levels of 542.4+/-63.1, 907.6+/-154.9, and 106.0+/-2.7 mg/dL (mean+/-standard deviation [SD]), respectively. At this time, increase in beta-cell replication was also observed, although this reached maximum by day 6 (p <0.001). Replication was also present in acinar cells, but these cells showed their maximum at day 3 (p <0.001) and subsequently decreased, as did beta-cells, almost steadily to normal values by day 12. Neogenesis of beta-cells was observed mainly as transdifferentiation from acinar cells at day 3 and from ductal cells at day 6, after which it tended to be normal. CONCLUSIONS: Male Sprague-Dawley rats receiving a single i.p. alloxan dose tended to normalize their endocrine function by day 12 after alloxan administration. This process included both regeneration and neogenesis of pancreatic beta-cells from either ductal or acinar cells.

[Pancreatic beta-cell neogenesis and regeneration]. / Neogénesis y regeneración de las células beta pancreáticas.

OBJECTIVE: To review the literature on beta-cell neogenesis and regeneration, with special interest in substances that regulate such processes. DESIGN: Representative papers were selected through a computer MEDLINE search from 1990 to 2000. RESULTS: Several studies showed that once islets of Langerhans developed from small pancreatic ducts, this process did not continue in normal adult individuals. However, it has been published that new beta-cell formation can occur in vivo in certain experimental models through neogenesis, in which gene pax 4 is extremely important. On the other hand, substances that stimulate the regenerative process of beta-cells include glucose, several hormones and certain growth factors. CONCLUSIONS: Substances that stimulate the regenerative process commonly express this effect in elevated, non-physiologic concentrations; thus, their possible therapeutic importance is not yet clear. Nevertheless, the Reg protein, present in regenerative pancreas and implied in neogenesis process, has actual possibilities of becoming therapeutically important.