Premium
Oral NF‐κB blockade attenuates pro‐inflammatory cytokines in the hypothalamic paraventricular nucleus of streptozotocin‐induced diabetes
Author(s) -
Kang YuMing,
Lei JingHui,
Ma Ying,
Guo Zheng,
Sun YaoJun,
Qin DaNian,
Zheng JinPing,
Francis Joseph
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.990.6
Subject(s) - streptozotocin , pyrrolidine dithiocarbamate , endocrinology , medicine , diabetes mellitus , oxidative stress , chemistry , proinflammatory cytokine , tumor necrosis factor alpha , inflammation , nf κb
A growing body of evidence suggests that inflammatory molecules contribute to the pathogenesis of diabetes. In this study, we explored the role played by inflammatory molecules in the central nervous system in the progression of streptozotocin‐induced diabetes. Adult male Sprague‐Dawley rats were injected with streptozotocin (STZ, 65 mg/kg, ip) to induce diabetes, and treated for 4 weeks with the NF‐κB inhibitor pyrrolidine dithiocarbamate (PDTC, 150mg/kg/day) orally or vehicle. Streptozotocin‐induced diabetic rats had higher levels of PICs (TNF‐α, interleukin (IL)‐1β and IL‐6) in plasma and in the hypothalamic paraventricular nucleus (PVN), and higher levels of Fra‐LI (an indicator of chronic neuronal activation), superoxide, p47 phox (a subunit of NAD(P)H oxidase) and NF‐κB activation (determined by phosphorylated IKKβ) in the PVN when compared with control rats. Treatments with PDTC for 4 weeks reduced the plasma levels of PICs, decreased Fra‐LI, superoxide, PICs, p47 phox and phosphorylated IKKβ in the PVN of the STZ‐induced diabetic rats. These findings indicate that PTDC, as a NF‐κB inhibitor, may have a beneficial effect on the diabetes by attenuating the pro‐inflammatory cytokines and inhibiting oxidative stress. Supported by NIH HL‐080544.