Synergistic protective effect of folic acid and vitamin B 12 against nicotine-induced oxidative stress and apoptosis in pancreatic islets of the rat.

FOLIC acid; VITAMIN B12; OXIDATIVE stress; ISLANDS of Langerhans; NICOTINE; LABORATORY rats

Context: Nicotine is an abundant and most significant component of cigarette smoke. Epidemiological evidence strongly suggests an association between cigarette smoking and pancreatic injury, although effects of smoking on endocrine pancreas are still controversial. Objective: We examined the impact and underlying mechanisms of action of folic acid and vitamin B12on nicotine-induced damage in pancreatic islets of rats. Materials and methods: Male Wistar rats were treated with nicotine (3 mg/kg body weight/d, intraperitonealy) with or without folic acid (36 µg/kg body weight/d, orally) and vitamin B12(0.63 µg/kg body weight/d, orally) for 21 d. Fasting blood glucose, oral glucose tolerance test, HBA1c, insulin, oxidative stress parameters, proinflammatory cytokines, and CRP level were measured. Histological evaluation, TUNEL assay, and immunohistochemical staining of NF-κB and caspase-3 were also performed. Results: Folic acid and vitamin B12blunted the nicotine-induced impairment in fasting blood glucose (51–56% recovery), HbA1c(64–76% recovery), oral glucose tolerance, insulin level (23–40% recovery), and islet cell counts (26–74% recovery) in rats. Moreover, folic acid in combination with vitamin B12also attenuated the nicotine-induced changes in markers of oxidative stress (17–88% recovery), TNF-α (40–99% recovery), and IL-6 level (47–65% recovery), CRP level (59–73% recovery), expression of NF-κB and caspase-3, and apoptosis in pancreatic islet cells. Discussion and conclusion: The present study shows that folic acid and vitamin B12supplementation can reduce nicotine-induced impairment in glucose homeostasis and apoptosis and damage of pancreatic islet cells by modulating oxidative stress, levels of proinflammatory cytokines, and expression of NF-κB. [ABSTRACT FROM AUTHOR]

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