The heart-protective mechanism of nitronyl nitroxide radicals on murine viral myocarditis induced by CVB3.
Our previous researches showed that nitronyl nitroxyl derivatives, NNP and NNVP were good anti-oxidants and provided radioprotective effects in C6 cells. The objective of the present study is to investigate the possible antiviral effects and underlying pharmacological of the two nitronyl nitroxide radicals against CVB3 in vitro and in vivo. The results showed that NNP and NNVP were some of the most potent compounds in terms of their antiviral effects by protecting myocardial cells against oxidative damage of free radicals. Treatment with NNP or NNVP could decrease the intracellular ROS level in vitro. They could lead to a significant decrease in activities of biochemical markers AST, CK and LDH in infected murine serum and could increase SOD and CAT activities and decreased MDA activities compared with infected control in vivo. NNP and NNVP could reduce NO production in infected mice by reacting with NO to produce the imino nitroxides which was confirmed by ESR spectrometry. In addition, NNP and NNVP could both decrease the mRNA expression of proinflammatory cytokines, TNF-α, IL-2 and IL-6. In conclusion, nitronyl nitroxide radicals NNP and NNVP were shown to have antiviral activities against CVB3 and they may represent potential therapeutic agents for viral myocarditis.
School of Pharmacy, Fourth Military Medical University, Xi'an 710032, PR China.
Haibo
H
Wang
Peng
P
Gao
Linlin
L
Jing
Xiangyang
X
Qin
Xiaoli
X
Sun
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D029822:Enterovirus B, Human / Q000187:drug effects / Q000472:pathogenicity*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D051379:Mice; D009205:Myocarditis / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D009569:Nitric Oxide / Q000096:biosynthesis; D009589:Nitrogen Oxides / Q000737:chemistry*; D009929:Organ Size / Q000187:drug effects; D011759:Pyrrolidines / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats
D000998:Antiviral Agents; D016207:Cytokines; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides; D011759:Pyrrolidines; D009569:Nitric Oxide; D008315:Malondialdehyde; C039900:nitroxyl