title: Experimental hyperprolinemia induces mild oxidative stress, metabolic changes, and tissue adaptation in rat liver.
abstract: The present study investigated the effects of chronic hyperprolinemia on oxidative and metabolic status in liver and serum of rats. Wistar rats received daily subcutaneous injections of proline from their 6th to 28th day of life. Twelve hours after the last injection the rats were sacrificed and liver and serum were collected. Results showed that hyperprolinemia induced a significant reduction in total antioxidant potential and thiobarbituric acid-reactive substances. The activities of the antioxidant enzymes catalase and superoxide dismutase were significantly increased after chronic proline administration, while glutathione (GSH) peroxidase activity, dichlorofluorescin oxidation, GSH, sulfhydryl, and carbonyl content remained unaltered. Histological analyses of the liver revealed that proline treatment induced changes of the hepatic microarchitecture and increased the number of inflammatory cells and the glycogen content. Biochemical determination also demonstrated an increase in glycogen concentration, as well as a higher synthesis of glycogen in liver of hyperprolinemic rats. Regarding to hepatic metabolism, it was observed an increase on glucose oxidation and a decrease on lipid synthesis from glucose. However, hepatic lipid content and serum glucose levels were not changed. Proline administration did not alter the aminotransferases activities and serum markers of hepatic injury. Our findings suggest that hyperprolinemia alters the liver homeostasis possibly by induction of a mild degree of oxidative stress and metabolic changes. The hepatic alterations caused by proline probably do not implicate in substantial hepatic tissue damage, but rather demonstrate a process of adaptation of this tissue to oxidative stress. However, the biological significance of these findings requires additional investigation.
authors: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil.
authors: Andréa G K
authors: AG
authors: Ferreira
authors: Aline A
authors: AA
authors: da Cunha
authors: Fernanda R
authors: FR
authors: Machado
authors: Carolina D
authors: CD
authors: Pederzolli
authors: Giovana R
authors: GR
authors: Dalazen
authors: Adriano M
authors: AM
authors: de Assis
authors: Marcelo L
authors: ML
authors: Lamers
authors: Marinilce F
authors: MF
authors: dos Santos
authors: Carlos S
authors: CS
authors: Dutra-Filho
authors: Angela T S
authors: AT
authors: Wyse
mesh_terms: D050842:1-Pyrroline-5-Carboxylate Dehydrogenase / Q000172:deficiency; D000592:Amino Acid Metabolism, Inborn Errors / Q000139:chemically induced* / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D002374:Catalase / Q000378:metabolism; D005260:Female; D005452:Fluoresceins / Q000378:metabolism; D005978:Glutathione / Q000032:analysis; D005979:Glutathione Peroxidase / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D011392:Proline / Q000008:administration & dosage*; D011394:Proline Oxidase / Q000172:deficiency / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D005452:Fluoresceins; D008055:Lipids; D017392:Thiobarbituric Acid Reactive Substances; C037631:2',7'-dichlorofluorescein; D006003:Glycogen; D011392:Proline; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D050842:1-Pyrroline-5-Carboxylate Dehydrogenase; D011394:Proline Oxidase; D005978:Glutathione