RESUMEN
Metabolic adaptations early in life can drive energy expenditure towards brain and physical development, with less emphasis on body mass gain and somatic growth. Dietary or pharmacological manipulations can influence these processes, but to date, the effects provided by riboflavin have not been studied. The study aimed to evaluate the effects of neonatal treatment with different doses of riboflavin on sensorimotor and somatic development in rodents. Based on this, the following experimental groups were formed: Control (C, 0 mg/kg), Riboflavin 1 (R1, 1 mg/kg), Riboflavin 2 (R2, 10 mg/kg) and Riboflavin 3 (R3, 100 mg/kg). Treatment with 100 mg/kg riboflavin anticipated the reflex ontogeny of righting, cliff aversion, negative geotaxis, and free-fall righting. Intervention with 10 and 100 mg/kg of riboflavin anticipated the reflex maturation of vibrissae placement. Eye-opening, upper incisor eruption, and lower incisor eruption reached maturational age more quickly for animals treated with 100 mg/kg, while caudal growth and body weight gain were reduced from the second week of treatment, for groups R2 and R3. Pearson's correlation analysis indicated a positive association between the administration of high doses of riboflavin and murine growth in the first week of treatment. There was, however, a negative association between treatment with a high dose of riboflavin and growth in the second week of administration, coinciding with a reduction in body weight gain in the R3 group. Treatment with 100 mg/kg of riboflavin also reduced energy expenditure parameters in the open field and catwalk. Although high-dose treatment stimulates the physiological plasticity of the CNS and reduces weight gain, hepatic parameters were preserved, highlighting the participation of the liver in the supply of fatty acids for neural maturation. Furthermore, hypothalamic NRF-1 expression was increased in the R3 group inversely to the reduction in weight gain. Our results suggest that high-dose riboflavin stimulates sensorimotor and somatic development and reduces the energy invested in growth, body weight gain, and locomotor activity, possibly involving NRF-1 gene modulation in the hypothalamus.
RESUMEN
Brain oxygen deprivation causes morphological damage involved in the formation of serious pathological conditions such as stroke and cerebral palsy. Therapeutic methods for post-hypoxia/anoxia injuries are limited and still have deficiencies in terms of safety and efficacy. Recently, clinical studies of stroke have reported the use of drugs containing riboflavin for post-injury clinical rehabilitation, however, the effects of vitamin B2 on exposure to cerebral oxygen deprivation are not completely elucidated. This review aimed to investigate the potential antioxidant, anti-inflammatory and neuroprotective effects of riboflavin in cerebral hypoxia/anoxia. After a systematic search, 21 articles were selected, 8 preclinical and 12 clinical studies, and 1 translational study. Most preclinical studies used B2 alone in models of hypoxia in rodents, with doses of 1-20â mg/kg (in vivo) and 0.5-5â µM (in vitro). Together, these works suggested greater regulation of lipid peroxidation and apoptosis and an increase in neurotrophins, locomotion, and cognition after treatment. In contrast, several human studies have administered riboflavin (5â mg) in combination with other Krebs cycle metabolites, except one study, which used only B2 (20â mg). A reduction in lactic acidosis and recovery of sensorimotor functions was observed in children after treatment with B2, while adults and the elderly showed a reduction in infarct volume and cognitive rehabilitation. Based on findings from preclinical and clinical studies, we conclude that the use of riboflavin alone or in combination acts beneficially in correcting the underlying brain damage caused by hypoxia/anoxia and its inflammatory, oxidative, and behavioral impairments.