Evaluation of Varied Modalities of Tocotrienol Supplementations to Counter the Cerebellar Oxidative Stress Caused by Low-to-moderate Doses of Ethanol in Rats

Abstract

Background and Aim: Self-intoxication with Ethanol (Et) is a common problem worldwide. Being a psychoactive drug, neurotoxic effects of Et are well known. Cerebellum is highly vulnerable to Et exposure. Tocotrienols (T3) are relatively rare components of vitamin E and have the potential to prevent the oxidative stress and act as neuroprotective. Varied modalities of T3 supplementations were evaluated to identify the possibilities of countering cerebellar oxidative stress caused by low-to-moderate doses of Et exposure. Methods: Four phase of experiments were carried out with nil (Et-0) and three doses of Et exposures (Et-I, Et-II and Et-III) for 4 weeks. In each phase, 4 groups of Wistar rats were maintained with sham supplementation (NT3), Prior Supplementation (PT3), Simultaneous Supplementation (ST3) and Total Supplementation (TT3) with T3 for 6 weeks. Cerebellar levels of reduced Glutathione (GSH), Lipid Peroxidation (LPO) and activities of catalase, Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and Glutathione Reductase (GR) were estimated and Superoxide and Peroxide Handling Capacities (SPHCs) were calculated. Results: All the tested cerebellar oxidative stress parameters and handling capacities were significantly influenced by the modalities of T3 supplementation. However, low-to-moderate doses of Et exposures contributed significantly in alterations of LPO level, GPx activity, GR activity and glutathione-dependent SPHC of cerebellum. Conclusion: Critical evaluation of studied parameters suggest insufficient overall performance of ST3 type of supplementation, whereas, TT3 type of supplementation was the best among the modalities of T3 supplementation. However, excess T3 supplementation may not be beneficial in some cases of oxidative stress parameters and SPHC of cerebellum.

Tocotrienol supplementations ameliorate oxidative stress in thalamus of rats exposed to low-to-moderate doses of ethanol

“…As already reported, these ethanol exposures and varied modalities of T3 supplementation affected the changes in body weight in dose-and supplementation-specific ways. 11 For the thalamic GSH content, the influence of T3 supplementation was statistically significant without any significant interaction with the low-to-moderate doses of Et exposures. Among the supplementation modalities, thalamic GSH contents of TT3 groups were significantly higher than the others during all four phases of the study (Figure 2A).…”

“…Consumption of alcohol is on the rise in India and some other Asian countries and the trend is likely to endure beyond 2030 28 Rises in disposable income 28 and social acceptance towards alcoholic beverages 11 refute the WHO mandate of a 10% reduction in harmful uses of alcohol by 2025. Therefore, this work assessed the effectiveness of different modalities of T3 supplementation against the thalamic oxidative stresses caused by low-to-moderate dosages of Et exposures.…”

“…9 It can protect the lipid-rich body from the damaging effects of oxidative stress, including the brain. Remarkably, T3 also provides neuroprotection, which might be supplementary to the defense against oxidative stress 11 and that to even at nanomolar concentrations. 12,13 On the other hand, excess and long-term supplementation of T3 may cause a build-up of itself and potentially may have prooxidant and even neurotoxic effects in vitro.…”