Taurine Increases Zinc Preconditioning‐Induced Prevention of Nitrosative Stress, Metabolic Alterations, and Motor Deficits in Young Rats following Intrauterine Ischemia

Abstract

Oxygen deprivation in newborns leads to hypoxic-ischemic encephalopathy, whose hallmarks are oxidative/nitrosative stress, energetic metabolism alterations, nutrient deficiency, and motor behavior disability. Zinc and taurine are known to protect against hypoxic-ischemic brain damage in adults and neonates. However, the combined effect of prophylactic zinc administration and therapeutic taurine treatment on intrauterine ischemia- (IUI-) induced cerebral damage remains unknown. The present work evaluated this issue in male pups subjected to transient IUI (10 min) at E17 and whose mothers received zinc from E1 to E16 and taurine from E17 to postnatal day 15 (PND15) via drinking water. We assessed motor alterations, nitrosative stress, lipid peroxidation, and the antioxidant system comprised of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Enzymes of neuronal energetic pathways, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH), were also evaluated. The hierarchization score of the protective effect of pharmacological strategies (HSPEPS) was used to select the most effective treatment. Compared with the IUI group, zinc, alone or combined with taurine, improved motor behavior and reduced nitrosative stress by increasing SOD, CAT, and GPx activities and decreasing the GSSG/GSH ratio in the cerebral cortex and hippocampus. Taurine alone increased the AST/ALT, LDH/ALT, and AST/LDH ratios in the cerebral cortex, showing improvement of the neural bioenergetics system. This result suggests that taurine improves pyruvate, lactate, and glutamate metabolism, thus decreasing IUI-caused cerebral damage and relieving motor behavior impairment. Our results showed that taurine alone or in combination with zinc provides neuroprotection in the IUI rat model.

Prophylactic Zinc Administration Combined with Swimming Exercise Prevents Cognitive-Emotional Disturbances and Tissue Injury following a Transient Hypoxic-Ischemic Insult in the Rat

“…These results suggest that the increased CAT activity in the ischemic group reflects a response to oxidative stress, which is prevented by zinc combined with swimming. In addition, zinc decreases CAT activity in neonate rats [ 69 ] through the regulation of ERK phosphorylation [ 97 ].…”

“…The NO production was assessed by the accumulation of nitrites (NO 2 − ) by the modified technique of Griess as described previously [ 69 ]. The cerebral cortex and hippocampus were obtained 1 h after the memory test ( n = 5 rats in each group), mechanically homogenized in phosphate-buffered saline solution pH 7.4 (PBS), and centrifuged at 12,500 rpm for 30 min at 4°C by using a Z216MK microcentrifuge (HERMLE Labortechnik; Wehingen, Germany).…”

“…Malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) as an index of lipid peroxidation were measured in each group ( n = 5), following the procedure described previously [ 69 ]. The colorimetric reaction was performed in 200 μ L of the supernatant supplemented with 650 μ L of 10.3 mM N-methyl-2phenyl-indole (Sigma-Aldrich; Saint Louis, MO, USA), which was previously diluted in a mixture of acetonitrile: methanol (3 : 1) and 150 μ L of methanesulfonic acid (Sigma-Aldrich; Saint Louis, MO, USA).…”

“…The reaction was initiated by adding 330 μ L of H 2 O 2 (30 mM), and the absorbance was measured at 240 nm every 30 s for 2 minutes with a spectrophotometer (Lambda EZ-150; PerkinElmer Company; Waltham, MA, USA). The results were reported as the U min −1 /mg protein [ 69 ].…”

“…The values of cognitive tests, histopathology, and biochemical probes were expressed according to the modified HSPEPS [ 69 ], indicating the efficacy of one or more pharmacological strategies (Register # MX2020010357) treatments. A value lower than healthy was zero, equal to healthy was 1, and higher than healthy was 1.5 or 2, depending on the increasing grade ( Table 1 ).…”