RESUMEN
Isoflurane is a broadly used inhalation anesthetic that causes cognitive impairment in rodent models as well as humans. Although previous studies suggested an association between isoflurane exposure and neuro-inflammation, apoptosis and mitochondrial dysfunction, the pathogenesis of isoflurane-induced cognitive decline remains elusive. In the present study, 22-month-old male Sprague-Dawley male rats (n=96) were divided into three groups: Control (Cont), isoflurane (ISO) and MS-275 pre-treated groups. The rats were sacrificed following exposure to isoflurane and a cognitive test. The hippocampus of each animal was harvested for quantitative PCR, TUNEL staining and western blot analysis. Histone deacetylases (HDAC)-1, -2 and -3 exhibited a significant increase at the gene and protein expression levels, whereas negligible mRNA expressions were observed for genes HDAC 4-11 (P>0.05; compared with Cont). Pre-treatment with the HDAC inhibitor MS-275 significantly inhibited the increase in TUNEL-positive cells induced by isoflurane exposure (70.72% decrease; P<0.001; compared with ISO). Furthermore, MS-275 significantly decreased caspase-3 and Bax expression levels while increasing Bcl-2 protein expression. The isoflurane-induced changes in the MAPK pathway signaling proteins ERK1/2, JNK and p38 were also reversed with MS-275 pre-treatment. Finally, in a Morris water maze test, the time to find a hidden platform was reduced in MS-275 pre-treated rats, compared with the ISO group. Therefore, the present study provided insight into the effect of isoflurane exposure on neuronal apoptosis pathways, as well as cognitive decline via epigenetic programming of MAPK signaling in aged rats.
RESUMEN
Two in vitro trials were conducted to identify a peptide with antioxidant activity and immunoenhancement from cottonseed meal protein hydrolysate (CPH) for fish. Primary hepatocytes of Megalobrama amblycephala were treated with CPH. In experiment 1, CPH significantly increased aspartate aminotransferase (GOT), alanine aminotransferase (GPT), total superoxide dismutase (t-SOD), catalase (CAT), and lysozyme activities, as well as up-regulated SOD, CAT, antimicrobial peptides 1 (Leap 1) and Leap 2 mRNA levels (p < 0.05). However, CPH significantly down-regulated the expression of NADPH oxidase-2 (NOX2), Kelch-like-ECH-associated protein 1 (Keap1), NF-E2-related factor 2 (Nrf2) and BTB and CNC homolog 1 (Bach1) mRNA (p < 0.05) in fish hepatocytes. Experiment 2 showed that the molecular mass of CPH was distributed mainly in the 700-1024 Da range. Peptide 1 (P1) and P2 significantly decreased GOT and GPT activities in conditioned medium (p < 0.05); however, P4 and P6 did not affect GOT and GPT activities (p > 0.05). Furthermore, P4 significantly increased hepatocyte GOT, GPT, t-SOD, CAT levels and lysozyme activities (p < 0.05), up-regulated SOD, CAT, Leap1 and Leap2 mRNA expression levels, and down-regulated the expression of Nrf2 and NOX2 mRNA (p < 0.05) in fish hepatocytes. The above results indicated that CPH and P4 enhanced hepatocyte metabolism, as well as improved antioxidant capacities and innate immunity of blunt snout bream hepatocytes.
