Abstract
Nicotine is the major alkaloid present in cigarettes that induces various biochemical and behavioral changes. Nanonaringenin (NNG) and vitamin E are antioxidants that are reported to mitigate serious impairments caused by some toxins and oxidants. Thus, we aimed to investigate the efficacy of NNG, vitamin E, and their combinations to ameliorate behavioral, biochemical, and histological alterations induced by nicotine in rats. Adult male albino rats were randomly grouped into six equal groups (10 rats/group): control, N (nicotine 1 mg/kg b.w./day S/C from 15th to 45th day, 5 days a week), NNG (25 mg/kg b.w./day orally for 45 days), N + NNG, N + E (nicotine + vitamin E 200 mg/kg b.w./day orally), and N + NNG + E (nicotine + NNG + vitamin E at the aforementioned doses). Behavioral tests were conducted on day 15 and 30 postnicotine injection, while memory tests, brain neurotransmitters, antioxidants, and histopathological examination were examined at day 30 only. As a result, nicotine impaired rats' activity (hypoactivity and hyperactivity) and memory, induced anxiolytic and anxiogenic effects on rats, and altered neurotransmitters (acetylcholinesterase, serotonin, and dopamine), and redox markers (MDA, H2O2, GSH, and catalase) levels in brain homogenates. Thickening and congestion of the meninges and degeneration of the cerebral neurons and glia cells were observed. Cosupplementation with NNG, vitamin E, and their combination with nicotine was beneficial in the alleviation of activity impairments and improved short memory and cognition defects and exploratory behaviors. Our results indicate the antioxidant potential of NNG and vitamin E by modulating redox markers and neurotransmitters in the brain. Thus, data suggest that the prophylactic use of NNG, vitamin E, and/or their combination for (45 days) may have a successful amelioration of the disrupted behavior and cognition and biochemical and histopathological alterations induced by nicotine.
Highlights
Tobacco smoking caused death to 100 million persons worldwide in the 20th century and is expected to kill about one billion people in the 21st century if the same manners remain [1]. e major alkaloid that existed in cigarettes is nicotine (N) about 1–2 mg/ml and was detected in the smoker’s blood [2]
Nicotine activates the nicotinic acetylcholine receptors present in the brain [3]. e nAChRs activation enhances the liberation of various neurotransmitters such as acetylcholine, glutamate, dopamine (DA), noradrenaline (NDA), and gamma amino Journal of Toxicology butyric acid (GABA) in the brain [4, 5]. ese neurotransmitters play an important role in modulating a great number of behaviors, including locomotion, anxiety, exploration, learning, and memory [3]
Nicotine is implicated in the production of free radicals and reactive oxygen species (ROS) and generates oxidative stress [6, 7] which leads to mitochondrial dysfunction that causes neural death [8]. erefore, antioxidants are highly needed by brain for the high oxygen demands and long-life duration of the neurons [9]
Summary
Tobacco smoking caused death to 100 million persons worldwide in the 20th century and is expected to kill about one billion people in the 21st century if the same manners remain [1]. e major alkaloid that existed in cigarettes is nicotine (N) about 1–2 mg/ml and was detected in the smoker’s blood [2]. Nicotine is implicated in the production of free radicals and reactive oxygen species (ROS) and generates oxidative stress [6, 7] which leads to mitochondrial dysfunction that causes neural death [8]. Natural antioxidants have attracted more attention to face free radical damage in different tissues in rats induced by various oxidants [10,11,12,13,14]. Flavonoids are a group of natural products that have valuable biological activities, including antioxidant, anti-inflammation, and antitumor properties [15,16,17]. Vitamin E is an antioxidant that could compete for oxidative stress status, such as neurodegenerative diseases [22]. NG mitigated anxiety-like effects induced by iron and hypoxic stress in rats [29, 30]
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