Cyclophosphamide treatment evoked side effects on skeletal muscle monitored by DSC
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Cyclophosphamide treatment evoked side effects on skeletal muscle monitored by DSC Dénes Lőrinczy1 Received: 2 October 2019 / Accepted: 23 January 2020 © The Author(s) 2020
Abstract Polyneuropathy is defined as a simultaneous malfunction of several peripheral nerves, which could be a side effect of cancer therapy as well. Many kinds of drugs, supposedly cyclophosphamide, also can induce a disease classified as toxic polyneuropathy. It is well known that a severe problem in the locomotor activity can join to it. Recently, we have no enough information about the attacked points in the structure of muscle proteins, as well as about the change in the interaction of myosin actin. In the present study, we analyse this side effect on skeletal muscle (m. gastrocnemius) by differential scanning calorimetry (DSC), as an established thermal analysis method, to follow the possible consequence of drug treatment in the most important muscle protein. We used cyclophosphamide-treated in vitro animal model (guinea pig) with a comparable dosage and time handling of human protocol to show evidences of this drug-induced effects. According to our results, we could show a dose-dependent difference between thermal parameters (denaturation temperature and calorimetric enthalpy) of untreated and treated samples assigned to their contractile proteins (actin and myosin), which can be detected by DSC. It proved that we can create new possibilities in the detection and prognosis of expected and unwanted side effects of cyclophosphamide, such as change of locomotor activity joined to polyneuropathy. Keywords DSC · ATP hydrolysis cycle · Actin/myosin · Cancer · Cyclophosphamide
Introduction In the twenty-first century, malignancies are the second leading cause of death after cardiovascular disease in developed countries and show a slight upward trend. During chemotherapy, cyclophosphamide is an effective immunosuppressive drug with wide application field, e.g. haematologic malignancies and in each type of solid tumours, etc. [1]. It is the reason that appeared on the most important drugs’ list published by WHO in April, 2015 [2]. It is a good tool during polyneuropathy treatment, but in several cases, it can induct this disorder too [1]. Cyclophosphamide has a wide variety of attacked points, and depending on the affected area, sensory, motor or vegetative signs of disfunction could occur, which makes more difficult to find the correct diagnosis. Locomotive human activity is controlled by the central nervous system, and the
“commands” are conducted through the nerves to the muscles. The good muscle function this way depends on the actual structure/stage of nervous and muscle system, mainly on the conformation of myosin and actin and on their interaction as well as on the communication between them. Any damage or unexpected changes in protein structure caused by chemotherapeutic agents in any step will cause a malfunction. It was shown in animal model that the cyclophosphamide can cause dose-dependent effect in the thermal characteristic of
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