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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Assessment of thymoquinone effects on apoptotic and oxidative damage induced by morphine in mice heart
Cyrus Jalili1, Maryam Sohrabi1, Faramarz Jalili2
1Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Abstract:
Opioids bind to specific receptors that are located in the central nervous system (CNS) and many other organs such as cardiovascular tissue. Morphine binds to opioid receptors and can induce oxidative stress under some certain conditions. Thymoquinone (TQ) has shown many therapeutic effects such as anti-inflammatory, antioxidant and immunomodulatory ones. Considering the oxidative effects of morphine, antioxidant effects of TQ and effects of oxidative damage in various types of biomolecules, the present study was conducted to determine the effect of morphine plus TQ on the expression of apoptotic genes in the heart of male mice. Hence we used real-time PCR to identify alterations in mRNA expression of genes involved in apoptotic pathway, including p53, Bax and Bcl-2 between the morphine-treated and TQ plus morphine-treated mice. Serum nitric oxide (NO) (Griess assay) and total antioxidant capacity (TAC) were analyzed and compared. In the morphine group, compared to control group, a significant increase in P53 and Bax mRNA expression and a significant decrease in Bcl-2 mRNA expression were observed (p < 0.01). In TQ plus morphine groups, NO was decreased (P <0 .001) and TAC levels were increased significantly (P < .001). Interestingly, TQ (9 and 18 mg/kg) plus morphine caused a significant decrease in p53 and Bax and a significant increase in Bcl2 mRNA expression, compared to morphine-treated group (p < 0.01). Collectively, the results of this study indicated that TQ, as an antioxidant, can improve the apoptotic effects induced by morphine in the heart tissue of mice.
Insights
Thymoquinone (TQ) mitigates morphine-induced oxidative stress and apoptosis in male mouse hearts. This antioxidant compound improved apoptotic gene expression and restored antioxidant capacity, offering cardioprotective effects against morphine toxicity.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Molecular Biology
Background:
- Opioid receptors are present in the central nervous system and cardiovascular tissues.
- Morphine can induce oxidative stress, potentially leading to cellular damage.
- Thymoquinone (TQ) exhibits known antioxidant, anti-inflammatory, and immunomodulatory properties.
Purpose of the Study:
- To investigate the cardioprotective effects of Thymoquinone (TQ) against morphine-induced apoptosis in male mice.
- To analyze the impact of TQ on apoptotic gene expression (p53, Bax, Bcl-2) in cardiac tissue.
- To evaluate the influence of TQ on oxidative stress markers, including nitric oxide (NO) and total antioxidant capacity (TAC).
Main Methods:
- Real-time PCR was employed to quantify mRNA expression of apoptotic genes (p53, Bax, Bcl-2).
- Griess assay was used to measure serum nitric oxide (NO) levels.
- Total antioxidant capacity (TAC) was assessed to determine the overall antioxidant status.
- Mice were divided into control, morphine-treated, and TQ plus morphine-treated groups.
Main Results:
- Morphine administration significantly increased p53 and Bax mRNA expression while decreasing Bcl-2 mRNA expression.
- TQ treatment (9 and 18 mg/kg) in combination with morphine significantly reduced NO levels and increased TAC.
- TQ co-administration notably reversed the effects of morphine on apoptotic gene expression, decreasing p53 and Bax while increasing Bcl-2 mRNA levels.
Conclusions:
- Thymoquinone (TQ) demonstrates significant cardioprotective effects against morphine-induced apoptosis in mice.
- TQ's antioxidant properties help to ameliorate the detrimental effects of morphine on cardiac tissue.
- TQ represents a potential therapeutic agent for mitigating opioid-induced cardiotoxicity.
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