Protective effect of resveratrol on citrullinemia type I-induced brain oxidative damage in male rats


Citrullinemia Type I is an inborn error, which leads to accumulation of citrulline and ammonia in blood and body tissues. We evaluated the in vitro effects of citrulline, ammonia and the influence of resveratrol on oxidative stress parameters in the cerebrum of 30- and 60-day-old male Wistar rats. Citrulline (0.1, 2.5, 5.0 mM), ammonia (0.01, 0.1, 1.0 mM) and resveratrol (0.01, 0.1, 0.5 mM) were added to the assays to measure thiobarbituric acid reactive substances (TBA-RS), total sulfhydryl content and the activity of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Citrulline (2.5 and 5.0 mM) increased TBA-RS in the cerebellum of 30-day-old and in the cerebral cortex and cerebellum of 60-day-old. Citrulline (5.0 mM) increased SOD and reduced GSH-Px in the hippocampus of 30-day-old, whereas in the cerebellum it increased GSH-Px. In the cerebral cortex, 2.5 and 5.0 mM citrulline reduced GSH-Px. In 60-day-old, 2.5 and 5.0 mM citrulline increased SOD in the cerebellum, increased GSH-Px in the cerebral cortex and 5.0 mM citrulline reduced CAT and increased SOD in the cerebral cortex. Ammonia (0.1 and 1.0 mM) reduced the sulfhydryl content in the cerebral cortex of 30- and 60-day-old, 1.0 mM ammonia increased SOD and reduced GSH-Px in the cerebellum of 30-day-old and increased SOD in the hippocampus and cerebellum of 60-day-old. Resveratrol was able to prevent the majority of these alterations. Thus, citrulline and ammonia induce oxidative stress in the cerebrum of rats; however, resveratrol was able to exert antioxidant effects against these substances.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.


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This work was supported by the University of Joinville Region (UNIVILLE).

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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Larissa Delmonego, Thayná Patachini Maia, Karine Louize Vincenzi, Aline Barbosa Lima, Luana Carla Pscheidt, Letícia Eger, Daniela Delwing-de Lima and Débora Delwing-Dal-Magro. The first draft of the manuscript was written by Larissa Delmonego and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Daniela Delwing-de Lima.

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All procedures performed in studies involving animals were in accordance with the Ethics Committee for Animal Research of the University of Joinville Region (UNIVILLE), Joinville, Brazil, under the protocol number 010/2016 – PRPPG/CEP.

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Delmonego, L., Maia, T.P., Delwing-Dal Magro, D. et al. Protective effect of resveratrol on citrullinemia type I-induced brain oxidative damage in male rats. Metab Brain Dis 36, 685–699 (2021).

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  • Citrullinemia type I
  • Oxidative stress
  • Antioxidants
  • Resveratrol