PubMed Health⌕ Search

Biomedical subjects

C Di Padova

Publications and source records attributed to C Di Padova.

13 recordsLinked to original sources
PubMed1991

Bile and biliary lipid secretion in rats with hexachlorobenzene-induced porphyria. Effect of S-adenosyl-L-methionine administration.

We investigated liver morphology and biliary function in vivo in rats made porphyric by hexachlorobenzene (HCB). In one group of HCB rats we also evaluated whether S-adenosyl-L-methionine (SAMe), administered during the last 15 days of HCB treatment, attenuated liver injury and the accumulation of porphyrins (HCB + SAMe group). In HCB rats we found: (a) a 100% increase in liver weight; (b) a 500-fold increase in total liver porphyrins (TLP); (c) significantly increased serum bilirubin and cholesterol levels; (d) unchanged total bile flow (TBF) but enhanced levels of the bile acid independent fraction (BAIF); and (e) decreased excretion in bile of bile acids (BA), phospholipids (PL) and cholesterol (CHO) (58, 65 and 47%, respectively, expressed as mmol/min per kg liver). SAMe was found to partially reverse HCB-related effects. TLP levels were about 65% lower in HCB + SAMe treated rats than in HCB rats. However, while SAMe restored bile CHO excretion to control values, it did not influence bile excretion of BA, PL, or BAIF. In conclusion, HCB-induced porphyria was characterized by a complex derangement of liver morphology and biliary function that was unrelated to the extent of porphyrin accumulation in the liver.

Animals↗
PubMed1990

Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study.

Parenteral S-adenosylmethionine proved to be effective in reversing intrahepatic cholestasis in pregnant women. Based on these findings, a prospective multicenter, double-blind, placebo-controlled trial was planned to assess whether oral S-adenosylmethionine is effective in cholestatic patients with chronic liver disease. Accordingly, 220 inpatients (26% chronic active hepatitis, 68% cirrhosis, 6% primary biliary cirrhosis) with stable (1 month or more) at least twofold increases in serum total and conjugated bilirubin and alkaline phosphatase volunteered for the trial. Serum markers of cholestasis significantly (P less than 0.01) decreased after oral S-adenosylmethionine administration (1600 mg/day), and their values were significantly (P less than 0.01) lower than the corresponding values in the placebo group. S-adenosylmethionine significantly (P less than 0.01) improved subjective symptoms such as pruritus, fatigue, and feeling of being unwell, whereas placebo was ineffective. Two patients in the S-adenosylmethionine group and 9 controls (P less than 0.05) withdrew from the trial for reduced compliance because of inefficacy of treatment. Oral S-adenosylmethionine was tolerated to the same extent as placebo. In conclusion, short-term administration of oral S-adenosylmethionine is more effective than placebo in improving clinical and laboratory measures of intrahepatic cholestasis and offers a new therapeutic modality for the symptomatic management of this syndrome.

Administration, Oral↗
PubMed1990

Age-associated decline of hepatic handling of cholephilic anions in humans is reverted by S-adenosylmethionine (SAMe).

Decreased fluidity of hepatocyte plasma membrane may contribute to the age-associated changes of liver function. This study aimed at investigating whether the hepatic clearance of organic anions declines with age and whether S-adenosylmethionine (SAMe), a substance proven to be effective in reversing the age-related decrease of membrane fluidity, might influence this process. Nicotinic acid (NA) half-life and serum bilirubin pharmacokinetics after NA load (5.9 mumol/kg body weight i.v.) were studied in 10 healthy young males (YM) aged 14-28 years and in 10 healthy elderly males (EM) aged 65-81 years, before and after SAMe administration (800 mg/day intravenously for 10 days). At baseline, EM showed serum total bilirubin (STB) levels significantly higher than YM. Similarly, the bilirubinaemic mean curves, STB peak and STB time curve concentration after NA load, expressed as area under the curve (AUC), were significantly higher in EM than in YM (p less than 0.01). NA half-life was also significantly prolonged in the aged group (p less than 0.001). SAMe treatment was followed by a significant decrease of basal STB, STB peak and AUC of STB after NA load in EM (p less than 0.01 vs pre-treatment values) while NA half-life was significantly shortened in both groups (p less than 0.001). As NA and bilirubin share a common carrier protein for hepatic uptake, bilitranslocase, the changes observed in EM may be attributed to the reduced lateral mobility of hepatocyte plasma membrane proteins occurring with age. SAMe, by improving membrane fluidity, may increase the diffusion coefficient of bilitranslocase restoring the hepatic handling of organic anions.

Adolescent↗
PubMed1990

Protective effect of S-adenosyl-L-methionine in hepatic uroporphyria. Evaluation in an experimental model.

The potential use of S-adenosyl-L-methionine (SAMe) as therapy for human porphyria cutanea tarda was investigated in an experimental model of hepatic porphyria--that is, chronic treatment of female rats with 0.2% hexachlorobenzene (HCB) in the diet. Administration of SAMe (25 mg/kg subcutaneously twice daily) during the last 15 days of HCB administration halved porphyrin accumulation in the liver but did not alter HCB-induced massive inhibition of uroporphyrinogen decarboxylase. Equally unaffected were inhibition of glutathione peroxidase and stimulation of lipid peroxide formation induced by HCB. Hypothetically, the beneficial effect of SAMe on hepatic porphyrin accumulation might be linked to modifications of the cellular availability of adenosine triphosphate.

Animals↗
PubMed1990

S-adenosylmethionine for the treatment of intrahepatic cholestasis of pregnancy. Results of a controlled clinical trial.

Previous studies have shown that S-adenosylmethionine (SAMe) counteracts oestrogen-induced bile secretion failure. In order to confirm this anticholestatic activity, we conducted a single-blind clinical trial comparing SAMe with placebo in the treatment of women with intrahepatic cholestasis of pregnancy (ICP). Thirty patients in the last trimester of pregnancy were randomly assigned to receive either SAMe (800 mg/day i.v.) or placebo until delivery for a mean period of 18 days. After SAMe, the women exhibited significantly (p less than 0.01) lower levels of total bile acids, serum conjugated bilirubin and aminotransferases with respect to pretreatment levels as well as to the corresponding values of the placebo group. In addition, SAMe significantly reduced pruritus whereas placebo was ineffective. No adverse reactions on mother or child were recorded during SAMe treatment, and the follow-up of these cases showed an incidence of premature labour (earlier than 37 weeks of gestation) in 2 out of 15 vs 5 out of 15 cases in the placebo group. In conclusion, these findings document that SAMe is more effective than placebo in ameliorating subjective and objective parameters of ICP.

Adult↗
PubMed1979

Cicloxilic acid and the bile lipids in oral contraceptive users.

Cholesterol supersaturation of gallbladder bile induced by oral contraceptives is significantly reduced by the administration of cis-2-hydroxy-2-phenyl-cyclohexane-carboxilic acid (cicloxilic acid), a choleretic substance which has been demonstrated to exert an antilithogenic effect in the rat and in man.

Adolescent↗
PubMed1975

[Bile secretion].

The canaliculus is the primary site for the formation of bile. Here, active secretion of bile acids creates an osmotic gradient between bile and blood, crossed passively by water and solutes. Numerous experimental data point to the existence of a canalicular bile fraction that is independent of the active transport of bile acids and related to active sodium secretion. The bile ducts are not mere conduits for the passage of bile, but can also change its volume and composition by means of both absorption and secretion. Nervous, vascular, hormonal and pharmacological factors serve to modify bile secretion. In most cases, however, their mechanism of action is virtually unknown.

Adenosine Triphosphate↗
PubMedDate not supplied

A review of the studies on the clinical use of S-adenosylmethionine (SAMe) for the symptomatic treatment of intrahepatic cholestasis.

S-Adenosylmethionine (SAMe) proved to be effective in antagonizing bile secretion impairment induced by a wide range of hepatotoxins, including ethynylestradiol, taurolithocholate, chlorpromazine and alpha-naphthyl-isothiocyanate. The anticholestatic activity of SAMe may result from its role in the intermediate metabolism as this molecule is involved in transmethylation and transsulfuration reactions. Clinical experience, carried-out on more than 1,000 cholestatic patients, supports preclinical data. In particular, controlled clinical trials have documented that intravenous SAMe (800 mg/day) induced a significant decrease of biochemical parameters of cholestasis (serum total and conjugated bilirubin, serum total bile salts, and aminotransferases), as well as a significant improvement of pruritus in women with ICP compared with placebo. In addition, other studies provided the evidence that both parenteral (800 mg/day) and oral SAMe (1600 mg/day) significantly improves subjective (pruritus, fatigue, and general discomfort) and objective (serum total and conjugated bilirubin, and serum alkaline phosphatase) parameters of cholestasis in patients with intrahepatic cholestasis complicating chronic liver diseases compared with placebo. In all these trials, SAMe treatment has been well tolerated at the same extent as placebo. In conclusion, experimental and clinical investigations indicate that SAMe represents an effective and safe approach to the management of intrahepatic cholestasis.

Cholestasis, Intrahepatic↗