Heme oxygenase 1 (HO-1) and carbon monoxide were shown to normalize oxidative stress and inflammatory reactions induced by neuropathic pain in the central nervous system, but their effects in the locus coeruleus (LC) of animals with peripheral inflammation and their interaction with nitric oxide are unknown. In wild-type (WT) and knockout mice for neuronal (NOS1-KO) or inducible (NOS2-KO) nitric oxide synthases with inflammatory pain induced by complete Freund’s adjuvant (CFA), we assessed: (1) antinociceptive actions of cobalt protoporphyrin IX (CoPP), an HO-1 inducer; (2) effects of CoPP and tricarbonyldichlororuthenium(II) dimer (CORM-2), a carbon monoxide-liberating compound, on the expression of HO-1, NOS1, NOS2, CD11b/c, GFAP, and mitogen-activated protein kinases (MAPK) in the LC. CoPP reduced inflammatory pain in different time-dependent manners in WT and KO mice. Peripheral inflammation activated astroglia in the LC of all genotypes and increased the levels of NOS1 and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK 1/2) in WT mice. CoPP and CORM-2 enhanced HO-1 and inhibited astroglial activation in all genotypes. Both treatments blocked NOS1 overexpression, and CoPP normalized ERK 1/2 activation. This study reveals an interaction between HO-1 and NOS1/NOS2 during peripheral inflammation and shows that CoPP and CORM-2 improved HO-1 expression and modulated the inflammatory and/or plasticity changes caused by peripheral inflammation in the LC.
The inactivation potential of HHP treatment (200 MPa-2 min) was evaluated against Salmonella enterica serovar Typhimurium in cauliflower and mandarin by-product infusions at 37 and 10 °C. By-product infusions exerted a strong antimicrobial effect used alone, achieving 5 log cycles of bacterial reduction for cauliflower by-product infusion after 10 hours and for mandarin by-product infusion after 80 hours, at 37 °C. The HHP treatment caused only one log cycle of cellular damage, but when inoculated cauliflower or mandarin by-product infusions were subjected to HHP treatment the antimicrobial effect against S. Typhimurium was enhanced, achieving 5 log cycles of inactivation in 6 hours at 37 °C in both cases. Inactivation curves were adjusted to the Weibull equation and the kinetic parameters (b and n) were obtained. When HHP treatment was combined with by-product infusions, the inactivation rates were greater than when either of the by-product infusions was added separately. In conclusion, a synergistic antimicrobial effect against S. Typhimurium appeared to take place when HHP treatment was combined with cauliflower or mandarin by-product infusion. These infusions could be considered as an additional microbial control measure to guarantee the food safety and food quality of pasteurized food products that are stored under refrigeration.
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