Successful abrogation by thymoquinone against induction of diabetes mellitus with streptozotocin via nitric oxide inhibitory mechanism.
Nitric oxide (NO) is involved in the destruction of beta-cells during the development of type I diabetes mellitus (DM). We demonstrated the possibility of rescuing beta-cells by intervention with thymoquinone (TQ) using streptozotocin (STZ) rat diabetic model. The hyperglycemic and hypoinsulinemic responses to STZ were significantly abrogated in rats cotreated with TQ, and this abrogating effect has persisted for 1 month after stopping of TQ treatment. Unlike observations recorded after diabetic chronicity of 1month, where there was a significant reduction of both serum and pancreatic nitrites, a significant increase in both nitrites was observed within the first 3 days in STZ rats, with or without lipopolysaccharide (LPS) stimulation, compared with controls and the TQ-cotreated. In vitro production of nitrite was significantly higher by 3-day-diabetic macrophages with or without stimulation compared to control or TQ-treated ones. However, 1-month-diabetic macrophages showed insignificant decrease of nitrite which turned significant upon stimulation. TQ has no effect on either IkB degradation or NF-kB activation; however, it significantly inhibited both p44/42 and p38 mitogen-activated protein kinases (MAPKs) which contribute to the transcriptional machinery of inducible nitric oxide synthase and NO production. These data emphasize the protective value of TQ against development of type I DM via NO inhibitory pathway.
El-Mahmoudy
Abubakr
A
Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University-Benha Branch, 13736 Moshtohor, Egypt.
Shimizu
Yasutake
Y
Shiina
Takahiko
T
Matsuyama
Hayato
H
El-Sayed
Mossad
M
Takewaki
Tadashi
T
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D007328:Insulin / Q000097:blood; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000096:biosynthesis; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000032:analysis / Q000097:blood; D010179:Pancreas / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D051996:Transcription Factor RelA; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D016227:Benzoquinones; D001786:Blood Glucose; D020672:I-kappa B Proteins; D007328:Insulin; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D009573:Nitrites; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D013311:Streptozocin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; C003466:thymoquinone