The Roles of Melatonin and Vitamin E Plus Selenium in Prevention of Oxidative Stress Induced by Naloxone-Precipitated Withdrawal in Heroin-Addicted Rats

Abstract

The therapeutic effects of melatonin or vitamin E plus Se (vE + Se) on the restrain of the heroin withdrawal-induced oxidative stress were studied. For this, rats were divided into ten groups. The rats were injected by fixed or variable doses of heroin for 16 consecutive days, and naloxone was given 1 h after the last heroin injection. One hour after naloxone administration, some groups were treated with melatonin or vE + Se. After 1 h this, blood samples were taken, and the levels of malondialdehyde (MDA) and reduced glutathione (GSH) in whole blood, ascorbic acid, α-tocopherol, retinol, β-carotene, nitrite, nitrate, and ceruloplasmin levels in the serum were measured. Our findings showed that, naloxone administration precipitated the heroin withdrawal. This also increased the level of MDA and decreased the levels of GSH in blood. Melatonin or vE + Se administration prevented the rise in MDA levels and increased the GSH levels. On the other hand, there were some significant differences between α-tocopherol, retinol, β-carotene, nitrite, nitrate, and ceruloplasmin levels of experimental groups. Results of present study showed that heroin withdrawal increased the lipid peroxidation and depressed endogenous antioxidative systems. Additionally, melatonin or vE + Se administrations prevented lipid peroxidation and augmented endogenous antioxidant defense systems.

Study of Oxidants and Antioxidants in Addicts

“…Besides, an indirect correlation has been observed between drug habit and antioxidant vitamin status (9). Vitamin E and selenium administrations prevented lipid peroxidation and improved endogenous antioxidant defense systems (62).…”

Selenium–Vitamin E Combination and Melatonin Modulates Diabetes-Induced Blood Oxidative Damage and Fetal Outcomes in Pregnant Rats

“…In vivo, it is an effective pharmacological agent in reducing oxidative damage under conditions in which excessive free radical generation is believed to be involved [13,14,19] The ability of MLT to reduce LPO may stem from its function as a preventive antioxidant (scavenging the initiating radicals) or from as yet unidentified actions. Moreover, peroxynitrite has also been shown to be directly scavenged by MLT [31][32][33].…”

“…The protective effects of Se (as co-antioxidant) seem to be primarily associated with its presence in the selenoenzymes, which are known to protect DNA and other cellular components from oxidative damage. Furthermore, a large-scale randomized controlled trial found that a combination of Se and vitamin E reduced many cancer morbidity and mortality [13][14][15]. In light of this, we decided to use the lipophilic antioxidant vitamin E and Se together for antioxidative protection of streptozocin (STZ)-induced radical production in pregnant rat.…”

Oxidative Stress and Drugs of Abuse: An Update

“…Moreover, impairment of prooxidative/antioxidative homeostasis was found in plasma of human heroin addicts [44]. Interestingly, heroin withdrawal may also induce oxidative stress, since naloxone-precipitated withdrawal increased the levels of MDA in the blood of heroin-addicted rats [45].…”

“…Administration of heroin to mice induced a decrease in total antioxidant capacity in serum [43] and in antioxidant enzymes, such as SOD, catalase, and GPx in the brain, and elevated markers of oxidative damage of DNA, proteins and lipids [42]. Naloxone-precipitated heroin withdrawal in rats depressed blood antioxidant systems, which could be prevented by administration of melatonin or vitamin E plus selenium, the latter being an essential cofactor of GPx [45].…”