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.

Adenosine A1-A2A Receptor-Receptor Interaction: Contribution to Guanosine-Mediated Effects

“…For evaluating ROS generation, slices were incubated with 80 µM 2 ,7 -dichlorofluorescein diacetate (DCFH-DA; Sigma-Aldrich) for 30 min [23]. Then, subsequent to the OGD/reoxygenation protocol, slices were washed twice with KRB and maintained for 15 min before adding DCFH-DA.…”

Guanosine prevents nitroxidative stress and recovers mitochondrial membrane potential disruption in hippocampal slices subjected to oxygen/glucose deprivation

“…DCFH-DA is deacetylated by intracellular esterases to form nonfluorescent form 2′,7′-dichlorodihydrofluorescein (DCFH), which is rapidly oxidized by reactive oxygen and/or nitrogen species present in samples, producing the highly fluorescent compound desterified 2′,7′-dichlorofluorescein (DCF). Peak excitation and emission wavelengths for DCF occur at 480 and 525 nm, respectively [23].…”

L-Proline Prevents Endoplasmic Reticulum Stress in Microglial Cells Exposed to L-azetidine-2-carboxylic Acid

“…However, in animal models, hyperprolinemia has also been associated with the occurrence of neurological deficits [15], likely due to energy metabolism deficits, Na(+),K(+)-ATPase, kinase creatine, oxidative stress and excitotoxicity [15]. Other studies indicate that excessive L-proline triggers oxidative damage in the blood cells of rats and to the liver [47,48], consistent with the idea that a balanced intake of the amino acid is required to provide optimal CNS protection. In this study, we co-administered L-proline at a concentration that was 20 times lower than AZE (50 µM L-proline vs. 1000 µM AZE).…”