Docosahexaenoic acid activates the Nrf2 signaling pathway to alleviate impairment of spleen cellular immunity in intrauterine growth restricted rat pups

Abstract

Intrauterine growth retardation (IUGR) impairs immune function in children. IUGR is associated with an imbalance of oxidative stress and abnormal apoptosis. Therefore, an IUGR rats model was established to determine the antioxidant capacity and apoptosis in newborn IUGR rats and explored whether these effects were regulated after Docosahexaenoic acid (DHA) supplementation to rat pups. First, eight normal-birth-weight (NBW) and eight IUGR neonatal rats (a 10% low-protein diet) were used to obtain the antioxidant capacity and apoptosis in IUGR rat pups. Then, 32 newborn rats were randomly assigned to the normal birth weight (NBW), DHA supplementation for NBW (ND), IUGR, and DHA supplementation for IUGR (ID) groups. Starting from the 7th day after birth, DHA was given to the experimental group and the same volume of distilled water was given to the control group for 21 days. (1) DHA improved the serum and spleen CD4/CD8 ratios and IL-4 and IFN-γ mRNA expression. (2) DHA decreased the level of MDA, but increased T-AOC in serum and spleen. (3) DHA increased the protein expression of Bcl-2 while decreased Bax. (4) DHA increased protein expression of the Nrf2 signaling pathway and the downstream antioxidant genes GSH-PX and CAT. DHA may alleviate the impairment of spleen cellular immunity in IUGR rat pups by inhibiting oxidative stress and apoptosis related to the activation of Nrf2 signaling pathway.

Utilization of Biopolymer-Based Lutein Emulsion as an Effective Delivery System to Improve Lutein Bioavailability in Neonatal Rats

“…Lutein supplementation has shown dose-dependent enhancements in adult mice's immune functions, such as increased natural killer cell activity and lymphoproliferative response in the spleen [79]. While the specific functions of lutein in the neonatal spleen remain unclear, it may aid spleen development and immunomodulation [80,81]. In this study, the lutein emulsion group displayed higher spleen lutein concentration, potentially benefiting spleen development and neonatal rat immunity.…”

Docosahexaenoic Acid as Master Regulator of Cellular Antioxidant Defenses: A Systematic Review

“…The number of studies conducted on animal models is limited to 15 cases. Twelve of them involved rats [ 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ], whereas three were conducted in mice [ 43 , 67 , 68 ]. Seven studies were focused on the liver [ 43 , 55 , 56 , 59 , 60 , 61 , 68 ], six on the nervous system [ 58 , 59 , 61 , 62 , 63 , 64 ], three on plasma/serum [ 55 , 65 , 68 ], and only one study was reported for the kidney [ 56 ], retina [ 57 ], spleen [ 66 ], stomach [ 67 ], and erythrocytes [ 65 ].…”

“…Twelve of them involved rats [ 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ], whereas three were conducted in mice [ 43 , 67 , 68 ]. Seven studies were focused on the liver [ 43 , 55 , 56 , 59 , 60 , 61 , 68 ], six on the nervous system [ 58 , 59 , 61 , 62 , 63 , 64 ], three on plasma/serum [ 55 , 65 , 68 ], and only one study was reported for the kidney [ 56 ], retina [ 57 ], spleen [ 66 ], stomach [ 67 ], and erythrocytes [ 65 ]. In addition, four studies were carried out in normal conditions [ 55 , 56 , 61 , 65 ], four studies in association with injuries [ 43 , 59 , 63 , 64 ], and seven studies in both conditions [ 57 , 58 , 60 , …”

“…Among them, 13 studies measured the enzymatic activity [ 43 , 55 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 67 , 68 ], while 9 and 2 studies evaluated the antioxidant defenses at the post-transcriptional [ 43 , 55 , 56 , 57 , 58 , 60 , 63 , 67 , 68 ] and transcriptional level, respectively [ 55 , 66 ]. Furthermore, one study evidenced an increase in cellular oxidative markers [ 56 ], four studies found a decrease [ 57 , 63 , 64 , 67 ], and nine studies reported no noticeable effects [ 43 , 55 , 56 , 57 , 58 , 62 , 65 , 67 , 68 ].…”

“…Despite these limitations, 14 studies reported a promoting effect of DHA supplementation on at least one expression or activity of antioxidant molecules [ 43 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ], whereas only an individual study reported no effects [ 55 ].…”