Biomedical subjects

D Serra

Publications and source records attributed to D Serra.

At least 73 records · Page 4Linked to original sources

PubMed1985

Metabolic activation of hepatocarcinogens in chronic hepatitis B.

S9 fraction pools of liver biopsy samples, collected from 129 patients in two consecutive studies, were comparatively assayed for their ability to activate aflatoxin B1 (AFB1) and a tryptophan pyrolysate product (Trp-P-2) in a miniaturized Salmonella mutagenicity test system. Metabolic activation was not affected to a significant extent by most of the monitored variability factors, such as sex, alcohol, cigarette smoking and liver histology (minimal changes, chronic persistent (CPH) or active (CAH) hepatitis, CAH steatosis, or cirrhosis). Conversely, a significant enhancement of activation was observed for AFB1 in cases of mild CAH and especially for Trp-P-2 in hepatitis B virus carriers, irrespective of their histologic diagnosis.

Aflatoxin B1↗

PubMed1985

In vivo effects of N-acetylcysteine on glutathione metabolism and on the biotransformation of carcinogenic and/or mutagenic compounds.

N-acetylcysteine (NAC) was administered to rats in various combinations with an enzyme inducer (Aroclor 1254) and with depletors of reduced glutathione (GSH), i.e., diethyl maleate (DEM) and buthionine sulfoximine (BSO). NAC increased intracellular glutathione levels in erythrocytes and in liver and lung cells, and replenished its stores following depletion. It did not affect the concentrations nor the spectral properties of cytochromes P-450 in hepatic and pulmonary microsomes, whereas it stimulated, especially in Aroclor-pre-treated animals, cytosolic enzyme activities involved in NADP reduction (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), in glutathione reduction (GSSG-reductase) and in the reductive detoxication of xenobiotics by-passing formation of reactive oxygen species (DT-diaphorase). In vivo treatment with the drug enhanced detoxication by liver and lung S-12 fractions of direct-acting mutagens (ICR 191, epichlorohydrin, 4-nitroquinolino-N-oxide and dichromate) and counteracted opposite effects triggered by administration of GSH depletors. The metabolic activation of procarcinogens (aflatoxin B1, 2-aminofluorene, cyclophosphamide, benzo[a]pyrene, a tryptophan pyrolysate product and cigarette smoke condensate) was inhibited by NAC in uninduced rats, while it was further stimulated in Aroclor-pre-treated animals. Additional assays, performed also with other enzyme inducers (phenobarbital and 3-methylcholanthrene) suggested that the effect of NAC on the metabolic activation of procarcinogens depends on the balance between an increased production of mutagenic metabolites (prevailing in induced animals) and their binding by intracellular thiols (prevailing under normal conditions). Thus, due to its dual role as a nucleophile and as a SH donor, NAC appears to exert protective effects by modulating glutathione metabolism and the biotransformation of mutagenic/carcinogenic compounds. This may have clinical relevance, since NAC is administered to individuals, such as cigarette smokers, who are more heavily exposed to GSH depletors and to carcinogenic agents.

Acetylcysteine↗

PubMed1985

Prominent role of DT-diaphorase as a cellular mechanism reducing chromium(VI) and reverting its mutagenicity.

Rat liver postmitochondrial (S-12) fractions accounted for the bulk of the activity of whole cell homogenates in reducing chromium(VI) and accordingly in decreasing its mutagenicity. Both cytosolic (S-105) and microsomal fractions concurred to this process, which in all subcellular preparations tested was selectively induced by phenobarbital and especially by Aroclor 1254, but not by 3-methylcholanthrene. Cytosolic fractions were markedly more efficient in reducing chromium(VI) than microsomal fractions recovered from the same amount of tissue (liver or lung), although the latter preparations had a higher specific activity. The microsomal activity was exclusively NADPH dependent. A minor part of the cytosolic reduction was determined by nonenzymatic components, notably by some electron donors and chiefly by reduced glutathione, which proved to reduce chromium(VI) at physiological concentrations. However, also in cytosolic fractions, the most important contribution to chromium reduction was enzyme catalyzed, as shown by the following properties: thermolability; requirement for exogenous NADH or NADPH [supplied as such or in the form of a NADPH-generating system (S-9 mix)]; and saturation by chromium(VI). The likely involvement of DT-diaphorase in this metabolic process is supported by several findings, including its sharp pH dependence and its partial suppression by known inhibitors of this enzyme protein, such as p-chloromercuribenzoate, L-thyroxine, and dicumarol (which conversely did not counteract the metabolic deactivation of the other direct-acting mutagens 2-methoxy-6-chloro-9-[3-(2-chloroethyl)aminopropylamino]acridine 2HCl and epichlorohydrin). Similarly, cytosolic reduction of chromium(VI) was partially inhibited by selective metabolic depletors of both coenzymes of DT-diaphorase, i.e., NADPH and NADH. Pretreatment of rats with enzyme inducers (phenobarbital and 3-methylcholanthrene) stimulated the activity of DT-diaphorase in liver cytosolic fractions. A dramatic stimulation (35 to 40 times over untreated controls) was produced by Aroclor 1254, which also coinduced the liver cytosolic activity of enzymes involved in the glucose 6-phosphate-dependent pathway of both nicotinamide-adenine-dinucleotide phosphate and glutathione reduction (glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and glutathione reductase). In the lung cytosol, a slight yet significant stimulation of some of these enzyme activities was determined by the daily intratracheal instillations of high doses of chromium(VI) itself for 4 weeks, a condition which has been found to enhance the pulmonary metabolism of this metal ion.

Animals↗

PubMed1982

[The male gonad in an adrenometabolic syndrome. Morpho-functional findings].

The hormonal and morphological features of the hypogonad condition observed in patients with Cushing's disease have been examined. Endocrine functional exploration carried out in 5 male patient showed normal gonadotropin incretion and excretion levels alongside a reduced plasma level of testosterone and an excess of suprarenal androgens, particularly DHA. Cytomorphological observation of the testicle not only confirms the state of gonadic functional quiescence, but makes it possible to exclude the existence of possible intrinsic changes which make gonads unable to respond to tropin stimulus. It is considered that, as is observed in normal humans under corticosteroid load, the excess of glycocorticoids in Cushing's disease depresses testicular endocrine activity, without activating feedback with gonadotrophic hypophysis, since the suprarenal androgens replace testosterone in the counter-regulation mechanism.

17-Hydroxycorticosteroids↗

PubMed1977

Effect of adrenocorticotropic hormone on pure exocrine pancreatic secretion in man.

The effect of adrenocorticotropic hormone (ACTH) on pure exocrine pancreatic secretion was studied in 7 subjects with external transduodenal drainage of the main pancreatic duct performed after biliary tract surgery. Intravenous injection of 0.25 mg of ACTH during a prolonged intravenous infusion of secretin (0.5 clinical units per kg-hr) plus cholecystokinin (0.5 Ivy dog units per kg-hr) significantly reduced protein and lipase (both concentration and output) without affecting volume and bicarbonate secretion. The reduction appeared soon after ACTH injection (peak inhibition in the first 15-min period) and lasted about 75 min. The adrenocortical response to ACTH reached its peak at the 60th min. The mechanism by which the pituitary hormone selectively inhibits pancreatic enzyme secretion without affecting volume and bicarbonate remains to be clarified.

Adrenocorticotropic Hormone↗

PubMed1975