Apolipoprotein E(Centre Hospitalier Universitaire de Nimes)

The interaction between adenosine and dopamine is critically important in determining the incidence of oxygen convulsion. Simultaneous regulation of both adenosine and dopamine offers a superior approach to counteract oxygen convulsion, achieving a synergistic effect exceeding the sum of their individual impacts. These findings provide new directions and insights for future in-depth and systematic exploration of the pathogenesis of central nervous system oxygen toxicity.

Acrylamide (ACR) is a toxic, probably carcinogenic compound commonly found in fried foods and used in the production of many industrial consumer products. ACR-induced acute kidney injury is mediated through several signals. In this research, we investigated, for the first time, the therapeutic effects of phytochemicals apocynin (APO) and/or umbelliferone (UMB) against ACR-induced nephrotoxicity in rats and emphasized the underlying molecular mechanism. To achieve this goal, five groups of rats were randomly assigned: the control group received vehicle (0.5% CMC; 1 ml/rat), ACR (40 mg/kg, i.p.), ACR + APO (100 mg/kg, P.O.), ACR + UMB (50 mg/kg, P.O.), and combination group for 10 days. In ACR-intoxicated rats, there was a significant reduction in weight gain while the levels of blood urea, uric acid, creatinine, and Kim-1 were elevated, indicating renal injury. Histopathological injury was also observed in the kidneys of ACR-intoxicated rats, confirming the biochemical data. Moreover, MDA, TNF-α, and IL-1β levels were raised; and GSH and SOD levels were decreased. In contrast, treatment with APO, UMB, and their combination significantly reduced the kidney function biomarkers, prevented tissue damage, and decreased inflammatory cytokines and MDA. Mechanistically, it suppressed the expression of NLRP-3, ASC, GSDMD, caspase-1, and IL-1β, while it upregulated Nrf-2 and HO-1 in the kidneys of ACR-intoxicated rats. In conclusion, APO, UMB, and their combination prevented ACR-induced nephrotoxicity in rats by attenuating oxidative injury and inflammation, suppressing NLRP-3 inflammasome signaling, enhancing antioxidants, and upregulating Nrf-2 and HO-1 in the kidneys of ACR-induced rats.