Human Placental Extract Stimulates Liver Regeneration in Rats.

Abstract

The effect of human placental extract (HPE) on liver regeneration in rats was investigated. After intravenous administration of HPE to a-naphthylisothiocyanate (ANIT)-intoxicated rats, the labeling index in hepatocytes was significantly increased to a level 16.5 times higher than that of the control. A 1/500 dilution of HPE directly stimulated DNA synthesis of the hepatocytes in primary culture. HPE heated at 121 degrees C did not stimulate the labeling index in vivo or hepatocyte DNA synthesis in primary culture, suggesting that HPE contains heat-unstable but potent mitogens for hepatocytes. HPE contains hepatocyte growth factor (HGF), but the mitogenic effect of HPE cannot be explained by the effect exerted by HGF alone, since both the labeling index in vivo and hepatocellular DNA synthesis in vitro stimulated by HPE were much higher than those stimulated by HGF alone when the applied doses of HGF were set to be almost the same level between each case. When HPE was fractionated on a heparin-sepharose column, the mitogenic effect of HPE was found to be located mainly in the heparin-bound fraction. Hepatocyte DNA synthesis induced by this fraction was enhanced cooperatively by the heparin-unbound fraction, suggesting that there are some modulators in the heparin-unbound fraction which enhance the proliferative activity of the heparin-bound fraction by a synergetic mechanism. Both HPE and heated HPE completely recovered the biochemical marker activity for liver function (glutamic-pyruvic transaminase, GPT; alkaline phosphatase, ALP; lactate dehydrogenase, LAP; gamma-glutamyltransferase, gamma-GTP activities and the bilirubin concentration) almost to the control level in the serum of ANIT-intoxicated rats, indicating that HPE also contains a heat-stable fraction which repairs liver function.

Aspirin and Probenecid Inhibit Organic Anion Transporter 3–Mediated Renal Uptake of Cilostazol and Probenecid Induces Metabolism of Cilostazol in the Rat

“…7B). JBP485 is a dipeptide (Liu et al, 2000) with antihepatitis and gastrointestinal protective effects (Liu et al, 1998;Wu et al, 2008) that was first isolated from Laennec (Yang et al, 2009), a substrate of OAT1 and OAT3 (Zhang et al, 2010). We found that PCG, probenecid, JBP485, and aspirin inhibited the uptake of cilostazol in a concentration-dependent manner (Fig.…”

A Case of Recovery from Canine Destructive Cholangitis in a Miniature Dachshund

“…We used highdose (50-74 mg/kg/day) UDCA and human placental extract (HPE) for the dog on a trial basis. HPE contains several growth factors including hepatocyte growth factor (HGF) and can stimulate liver regeneration in rats with experimentally induced liver failure [7]. Although the relationship between these treatments and recovery in this case was unclear, no adverse effects associated with high-dose UDCA and HPE administration were encountered.…”

Efficacy and Safety of Human Placental Extract for Alcoholic and Nonalcoholic Steatohepatitis: An Open-Label, Randomized, Comparative Study

“…Reportedly, the constituents of HPE are quite diverse and include the followings: uracil, tyrosine, phenylalanine, L-tryptophan and collagen derived peptides [7][8][9] ; certain steroid hormones 10) ; cytokines such as hepatocyte growth factor (HGF). 11,12) Because of its strong antioxidant substances, anti-inflammatory mediators and growth factors, HPE may play a potential role in liver cell protection from such kind of hepatic injury. Therefore, in this study, we planned to evaluate the clinical value of HPE in terms of efficacy and safety for the treatment of liver diseases, especially ASH and NASH, and designed as a multicenter controlled clinical trial with an open-labeled randomized comparative non-inferiority study to improve the reliability.…”