Browsing by Author "Yurt K.K."

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Diclofenac sodium and hippocampus: A brief evaluation
(2021-01-26) Gasmalla H.E.E.; Yurt K.K.; Nurein M.A.; Kaplan S.
The purpose of this chapter is to highlight the relationship between oxidative stress (OS) as a mechanism by which diclofenac sodium (DS) can affect the hippocampus, the vulnerability of the hippocampus to OS, and the responsiveness of both DS and hippocampus to antioxidants. This review also explores other studies that evaluate the effect of DS on the hippocampus. The hippocampus is a part of the hippocampal formation (HF) that is involved in functions related to memory, learning, and emotions. DS as one of the non-steroidal anti-inflammatory drugs (NSAIDs) is a phenylacetic acid derivative, it is known as an anti-inflammatory, analgesic, and antipyretic drug. Studies suggest that the toxicity of DS is induced by OS and reduced by antioxidants; the hippocampus is a vulnerable region and affected by OS. It is also responsive to the protective roles of substances having antioxidant activities, considering this; many antioxidants have been proven to be neuroprotective. Several studies used antioxidants to minimize the effect of OS on the nervous tissues. It indicates the useful effect of antioxidants, on the other hand, randomized controlled trials have concluded that antioxidants have no significant effects on Parkinson disease (PD) and Alzheimer disease (AD), both diseases associated with OS. The probable explanation for unexpected result might be due to limitations regarding the generalization of the results obtained from animals on humans. It is a general rule that animal models cannot mimic the same long duration of disease development or ageing processes. Other factors include dosage differences between animal models and humans, and using an antioxidant that scavenges reactive oxygen species (ROS) rather than eliminating the source of their production is also a contributing factor. There are different mechanisms of OS with different sources of ROS, thus the use of multiple antioxidants would be more beneficial, also, it looks crucial to administer antioxidants in early stages or prior to disease development, more work in this field is needed.
Dose-dependent effects of diclofenac sodium on the nervous system
(2021-01-26) Kaplan A.A.; Yurt K.K.; Marangoz A.H.; Ragbetli M.Ç.; Kaplan S.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are prostaglandin inhibitors used for the alleviation of pain, inflammation, myocardial infarction and stroke. Prostaglandins are also important chemical mediators in the human body, being involved in both normal and abnormal functioning of organs and systems. Diclofenac sodium (DS) is reported to cross from the human placenta to the foetus during the first and second trimesters. The drug crosses the placental barrier to prevent the biosynthesis of prostanoids and passes into the foetal circulation, where it causes significant side-effects and sometimes malformations in newborns. Experiments have suggested that exposure to DS during the prenatal period produces teratogenic effects on the CNS and neuroanatomical anomalies in animal models. However, it has also been suggested that used in low doses, DS may produce beneficial effects on neurological systems, especially in terms of prenatal development. The aim of this chapter is to fill this knowledge gap by means of quantitative and qualitative analysis in order to identify the probable neuroprotective/neurotoxic effect on the nervous system of DS administration in differing doses. Another aim is to report potential results regarding its use during the prenatal period. The chapter will also add further information to the existing literature regarding the effects of DS on the spinal cord, brain, cerebellum and peripheral nerves.
Melatonin neuroprotection of the hippocampus exposed to diclofenac sodium during pre- and postnatal life
(2021-01-26) Yurt K.K.; Kaplan S.
Diclofenac sodium (DS), a phenyl acetic acid derivative, is a potent inhibitor of cyclooxygenase that has been extensively used worldwide for many years in the treatment of inflammation and pain. However, despite these benefits, it also exhibits numerous adverse effects on the central nervous system, especially when used prenatally. Melatonin (MLT) is a neuroendocrine substance largely produced in the brain. It has been shown to exhibit several properties, including antioxidant, anti-inflammatory, and antiapoptotic effects, and acts as a neuroprotective agent. MLT exhibits pleiotropic neurobiological effects via cell membrane receptors. Pyramidal and granular neurons in the hippocampus contain MLT membrane receptors (MT1 and MT2). In this chapter, we discuss the cellular and molecular mechanisms of DS-induced reactive oxygen species generation in the hippocampus, the molecular targets, and responses, how oxidative stress affects hippocampus functions, and the MLT mechanism of action in terms of potential protection against DS-induced toxicity.
Peripheral nerve system and nonsteroidal anti-inflammatory drugs: molecular, morphological, and clinical approaches
(2021-01-26) Altun G.; Kaplan A.A.; Yurt K.K.; Kaplan S.
Nonsteroidal anti-inflammatory drugs (NSAIDs) show its action by inhibiting the enzyme cyclooxygenase (COX); reduce pain and fever and stop inflammation at higher doses. Often, they may show cardiotoxic and renal side effects, notably on gastrointestinal system. Beside of them, it has also neurotoxic effects on the central and peripheral nervous system. Diclofenac sodium (DS), an NSAID drug, is a non-selective COX inhibitor. Experimental studies have pointed out various antioxidants against DS-based neurotoxicity occurring in the central and peripheral nervous system. Although the side effects of these drugs, they are often preferred for the treatment of peripheral neuropathic pain. Recent studies suggest that combinations with other types of drugs would be more effective in the treatment of neuropathic pain. In addition, current studies tend to explore the role of new herbal-derived pharmaceutical molecules in the treatment of neuropathic pain. In this regard, there are no enough clinical and experimental studies that are controversial on the effectiveness and safety of herbal-based treatments. In this chapter, it was aimed to discuss the effect of NSAIDs on the neuropathic pain and sciatic nerve morphology in terms of molecular, experimental, and clinical approaches, considering the pharmacological properties and side effects of NSAIDs.
Prenatal administration of non-steroidal anti-inflammatory drugs and optic nerve development
(2021-01-26) Kivrak E.G.; Kaplan A.A.; Yurt K.K.; Kaplan S.
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used by women of reproductive age to alleviate conditions such as fever, pain and inflammation. These drugs, especially when taken during pregnancy, can cause adverse effects, depending on the duration of treatment and dosage employed, in the foetal and newborn periods. Although prenatal exposure to NSAIDs causes adverse effects on the developing central nervous system (CNS) and peripheral nervous system (PNS), these have not yet been fully explained. Prenatal NSAIDs administration can also cause changes in the morphology of optic nerve fibres, such as reducing the myelin sheath thickness and decreasing the numerical density of the developing optic nerve. One of the side-effects of NSAIDs on the CNS is impaired nerve cell signalling due to the apoptotic and / or necrotic process created by oxidative stress. It is recommended that NSAIDs be used with caution until maternal effects are more severe than teratogenic risks and patients are more informed about their side effects. This chapter evaluates the effects of prenatal NSAID exposure on the development of the optic nerve using stereological, histological and electron microscopic techniques.
Prenatal diclofenac sodium exposure and sertoli cells: A light and electron microscopic evaluation
(2021-01-26) Deniz Ö.G.; Kaplan A.A.; Annaç E.; Yurt K.K.; Kaplan S.
Developing technology and global free trade have together created a consumer society in the field of health, and this has in turn increased the consumption of drugs. The use of non-steroidal anti-inflammatory drugs (NSAIDs), with their toxic effects, has also increased considerably in recent years. The teratogenic potential of these drugs during pregnancy, their effects on fetal organs, fetal growth, and their neonatal and long-term effects in children all require consideration. NSAIDs given to pregnant women cross the placenta and may cause adverse embryo-fetal and neonatal effects, depending on the type of drug administered, the dose and length of treatment, and the duration of pregnancy. Placental transition continues in all cases, independently of gestational age. The half-life of these drugs is longer in the fetal circulation (14.7 hours) than in the maternal circulation (2.2 hours). The fetus is therefore more exposed to the deleterious effects of the drug. These effects result from the mechanisms of action of NSAIDs and physiological changes in drug pharmacokinetics in the gestational period. Diclofenac sodium (DS) is a commonly used NSAID among women of reproductive age. The use of these drugs during pregnancy is reported to be capable of leading to developmental disorders in both human and animal embryos, since they cross the placental barrier and affect the fetus. This drug inhibits the biosynthesis of prostaglandins, cross the placental barrier, get into fetal circulation, and exhibit toxic effects in organs such as the brain, kidney, ovary and testis. Sertoli cells are the somatic cells of the testis with an important role in spermatogenesis and testis formation. In this context; this chapter discusses in detail the effects of the prostaglandin synthesis inhibitor DS on the development of Sertoli cells in terms of light and electron microscopy, particularly its use during pregnancy, and is intended to contribute to the current scientific literature.