Lithium reverses the effect of opioids on eNOS/nitric oxide pathway in human umbilical vein endothelial cells

Nezamoleslami, Sadaf; Sheibani, Mohammad; Mumtaz, Faiza; Esmaeili, Jamileh; Shafaroodi, Hamed; Dehpour, Ahmad Reza

doi:10.1007/s11033-020-05740-9

Cited by 7 publications

(5 citation statements)

References 40 publications

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“…It was demonstrated that the repeated morphine treatment causes an increase in the secretion of some mediators including NO (17). Inhibition of NOS and the prevention of NO overproduction diminished morphine tolerance (25). Studies provided evidence that blockade of NO with aminoguanidine could decrease the development of morphine tolerance and dependence through the inhibition of iNOS, revealing the involvement of iNOS in these phenomena (10,26).…”

Section: Discussionmentioning

confidence: 99%

The Expression and Function of Nitric Oxide Synthase Enzyme in Atorvastatin Effects on Morphine-Induced Dependence in Mice

et al. 2021

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Background: Atorvastatin exerts neuroprotective effects on the treatment of central nervous system disorders. Morphine analgesic tolerance and dependence remain as major concerns in medicine. Nitric oxide (NO) pathway mediates the development of opioid analgesic tolerance and dependence, as well as atorvastatin neuroprotection. Objectives: The present study aimed to assess the possible involvement of the NO/cGMP pathway in the process of the effects of atorvastatin on morphine physical dependence. Methods: Dependence was induced by repetitive injection of morphine sulfate. Naloxone was injected at the dose of 4 mg/kg on the last day of the experiment to assess withdrawal signs. Animals received atorvastatin (1, 5, 10, and 20 mg/kg, orally). Nitric oxide synthase (NOS) inhibitors and ODQ were injected before protective dose atorvastatin. The gene expression of NOS isoforms was evaluated by real time-PCR. Thereafter, the hippocampal levels of cGMP and nitrite were measured. Results: Treatment with atorvastatin 10 mg/kg significantly attenuated naloxone-induced withdrawal behaviours. The administration of L-NAME, aminoguanidine, and ODQ before atorvastatin enhanced its effects. The treatment with atorvastatin significantly decreased the nitrite and cGMP levels as well as NOS gene expression in the hippocampus of dependent animals. Conclusions: It can be concluded that atorvastatin, possibly, through inducible NOS, could alleviate morphine dependence and withdrawal signs.

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Section: Discussionmentioning

confidence: 99%

The Expression and Function of Nitric Oxide Synthase Enzyme in Atorvastatin Effects on Morphine-Induced Dependence in Mice

et al. 2021

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“…The neurogenic relaxation of the cavernosal smooth muscle is also mediated by neuronal NO, as the NANC transmitter, generated by the nNOS activity [ 35 ]. Lithium may affect these processes via several mechanisms, including ( Figure 2 ): (i) inhibitory effects on inositol cycle and depletion of inositol via inhibiting inositol phosphatases [ 93 ], (ii) decreasing IP 3 -induced Ca 2+ current from the endoplasmic reticulum (ER) to the intracellular space and reducing ER Ca 2+ stores [ 94 , 95 , 96 , 97 ], (iii) possible inhibitory effects on either eNOS or nNOS activity as evidenced by lithium-induced decreased NO metabolites or L-citrulline in various tissues including blood as well as decreased eNOS expression in human umbilical vein endothelial cells [ 13 , 51 , 52 , 98 ].…”

Section: Lithium and Sexual Dysfunctionmentioning

confidence: 99%

“…Another study found that indomethacin potentiated the acetylcholine-induced relaxation of the isolated aorta from chronic lithium-treated rats [ 89 ]. Lithium was also found to decrease cAMP levels in the rat cortex [ 103 ] and human umbilical vein endothelial cells [ 98 ].…”

Section: Lithium and Sexual Dysfunctionmentioning

confidence: 99%

“…Neurogenic relaxation of the cavernosal smooth muscle is also mediated by neuronal NO, generated by the neuronal NOS (nNOS) activity in the cavernosal nerves [ 35 ]. Lithium can also decrease eNOS and nNOS activities as evidenced by decreased eNOS expression in vascular tissues as well as NO metabolites in brain tissues [ 51 , 52 , 98 ]. ATP, adenosine triphosphate; CaM, calmodulin; cGMP, cyclic guanosine monophosphate; GC, guanylyl cyclase; GTP, guanosine triphosphate; PK, protein kinase; PKG, protein kinase G; PIP 2 , phosphoinositide 4,5-biphosphate; VDCC, voltage-dependent calcium channel.…”

Section: Figurementioning

confidence: 99%

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Lithium and Erectile Dysfunction: An Overview

Sheibani

Ghasemi

Dehpour

2022

Cells

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Lithium has been a mainstay of therapy for patients with bipolar disorders for several decades. However, it may exert a variety of adverse effects that can affect patients’ compliance. Sexual and erectile dysfunction has been reported in several studies by patients who take lithium as monotherapy or combined with other psychotherapeutic agents. The exact mechanisms underlying such side effects of lithium are not completely understood. It seems that both central and peripheral mechanisms are involved in the lithium-related sexual dysfunction. Here, we had an overview of the epidemiology of lithium-related sexual and erectile dysfunction in previous clinical studies as well as possible pathologic pathways that could be involved in this adverse effect of lithium based on the previous preclinical studies. Understanding such mechanisms could potentially open a new avenue for therapies that can overcome lithium-related sexual dysfunction and improve patients’ adherence to the medication intake.

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“…It was proven that Activation of NMDA receptors leads to activation of nitric oxide (NO) synthase and subsequent NO production 6 . As a result, NO has a role in opioid dependence and tolerance 7 .…”

Section: Introductionmentioning

confidence: 99%

Stevia Extract and MK-801 Attenuate Nalbuphine Tolerance and Dependence in Mice: Role of Glutamate, Nitric Oxide, and Oxidative stress

Ali

2023

Sphinx Journal of Pharmaceutical and Medical Sciences

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This study aimed to investigate for the first time, the potential role of stevia aqueous extract alone and in combination with MK-801 on nalbuphine-induced tolerance and dependence in mice using biochemical and histological tools. In this study, Repeated administration of stevia extract (300 mg/kg, p.o) along with nalbuphine (10 mg/kg, s.c.) attenuated the development of tolerance, as measured by the hot plate test, and dependence, as assessed by naloxone (5 mg/kg, i.p.) -precipitated withdrawal manifestations. Concomitantly, increase in brain glutamate level, malondialdehyde level, and serum nitrite level-induced by repeated administration of nalbuphine to mice or by administration of naloxone to nalbuphine-dependent mice were inhibited by co-administration of stevia extract. Also, co-administration of the stevia extract inhibited the decrease in brain intracellular reduced glutathione level and glutathione peroxidase activity induced by both treatments. The inhibitory effect of the extract on nalbuphine-induced tolerance and dependence and on naloxone-induced biochemical alterations in nalbuphine-dependent mice was enhanced by concurrent i.p. administration of the NMDA receptor antagonist, MK-801 (0.25 mg/kg). histopathological results revealed that stevia extract coadministration produced decrease in nerve cell degeneration, vacuolation, apoptosis and enhance neuropil appearance. This histopathological improvement increased by concurrent administration of MK-801 with stevia extract. These results provide evidence that stevia extract appears to have a therapeutic potential in opioid tolerance and dependence, through inhibition of nalbuphine-induced elevation in glutamate level, NO overproduction and oxidative stress.

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Lithium reverses the effect of opioids on eNOS/nitric oxide pathway in human umbilical vein endothelial cells

Cited by 7 publications

References 40 publications

The Expression and Function of Nitric Oxide Synthase Enzyme in Atorvastatin Effects on Morphine-Induced Dependence in Mice

The Expression and Function of Nitric Oxide Synthase Enzyme in Atorvastatin Effects on Morphine-Induced Dependence in Mice

Lithium and Erectile Dysfunction: An Overview

Stevia Extract and MK-801 Attenuate Nalbuphine Tolerance and Dependence in Mice: Role of Glutamate, Nitric Oxide, and Oxidative stress

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