Ajoene restored behavioral patterns and liver glutathione level in morphine treated C57BL6 mice

Abstract

Oxidative stress exacerbates drug dependence induced by administration of opiate analgesics such as morphine-induced tolerance and physical dependence associated with the reduction in hepatic glutathione (GSH) level. Ajoene obtained from garlic (Allium sativum L.) has been reported for anti-tumorigenic, anti-oxidative and neuroprotective properties, however, little is known about its effect on morphine-induced dependence. Therefore, this study aimed at the effect of ajoene on physical and/or psychological dependence and liver GSH content in morphine-treated mice. Conditioned place preference (CPP) test and measurement of morphine withdrawal syndrome were performed in C57BL6 mice for behavioral experiments. Thereafter, mice were sacrificed for measurement of serum and liver GSH levels. Ajoene restored CPP and naloxone-precipitated jumping behavior in mice exposed to morphine. Moreover, the reduced level of liver GSH content in morphine treated mice was back to normal after ajoene administration. Taken together, ajoene improved behavioral patterns in mice exposed to morphine suggesting its potential therapeutic benefit against morphine-induced dependence.

Genistein Improves Liver Damage in Male Mice Exposed to Morphine

“…Morphine can cause injuries to liver and renal tissues. [ 5 12 ] Oxidative stress is a factor greatly involved in the liver damage caused by drugs and toxins. The increased activity of liver enzymes in serum indicates hepatic damage, which leads to the reduced performance of liver cells.…”

“…Morphine is mainly metabolized in the liver and its consumption increases the liver toxicity. [ 11 ] Based on the study results of Yun et al .,[ 12 ] morphine has been introduced as a toxic and lethal factor for liver cells. Antioxidants in foodstuff can protect the cells against various types of oxidative damage caused by free radicals.…”

Glutathione and Glutathione-Like Sequences of Opioid and Aminergic Receptors Bind Ascorbic Acid, Adrenergic and Opioid Drugs Mediating Antioxidant Function: Relevance for Anesthesia and Abuse

“…Morphinone binds covalently to proteins in liver specifically at cysteines to produce morphinone–cysteine adducts that interfere with protein function [ 27 , 28 , 29 , 30 ]. This adduct reaction is inhibited, and protein function maintained, by the presence of sulfhydryl compounds such as glutathione and L-cysteine [ 28 , 31 ], S -adenosyl- l -methionine [ 32 ], and the disulfide-containing garlic compound ajoene (( E )-1-(prop-2-enyldisulfanyl)-3-prop-2-enylsulfinylprop-1-ene) [ 33 ]. The mechanism of this protection appears to be a competition reaction: morphinone reacts covalently with the sulfur-containing compounds in preference to the proteins.…”

The effect of morphine on development of ulcer lesions of the rats exposed to indomethacin induced stress

“…U nekim radovima se pominje da je hronična primena morfina dovela do oštećenja jetre kod pacova i miševa koji su razvili toleranciju i fizičku zavisnost prema istom [18,41]. Kod tretiranih životinja zabeležen je značajan pad u sadržaju redukovanog glutationa (GSH) u jetri (do 40%), ali i aktivnosti superoksid dizmutaze (SOD), katalaze (CAT) i glutation S transferaze (GST), ali i povećan nivo malondialčdehida (MDA), kao indeksa lipidne peroksidacije [18,41,42].…”

“…O uticaju morfina na razvoj oksidativnog stresa postoje vrlo kontradiktorni podaci, većina autora tvrdi da on izaziva oksidativni stres, ali ima i onih koji tvrde suprotno, tj. da deluje antioksidantno [16,17,18]..…”