Retrospection of the effect of hydroxyurea treatment in patients with sickle cell disease

Verma, Henu Kumar; Lakkakula, Saikrishna; Lakkakula, Bhaskar V.K.S.

doi:10.2478/ahp-2018-0001

Cited by 18 publications

(12 citation statements)

References 68 publications

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“…The main liability during HU therapy is myelosuppression, that is, decline in RBC and hemoglobin (Hb) levels. 4 The present study results of HU on key hematological parameters in the rat model are similar to the previously reported observations. 16 − 18 Concomitant treatment of andrographolide (100 mg/kg, oral) in the presence of HU showed significant boosting of the RBC level ( p < 0.01) when compared with the treatment of HU alone.…”

Section: Resultssupporting

confidence: 93%

“…HU is an anticancer drug, and therefore, myelosuppression is a major adverse effect associated with its treatment. 4 In this context, preclinical as well as clinical studies are ongoing worldwide to improve the pathophysiological conditions of the SCA patients depending upon the different targets, viz. decline in sickling behavior, reduction in oxidative stress, enhancement of HbF production, lessening of platelet aggregation, lowering of adhesion behavior, reduction in inflammation, and so on.…”

Section: Introductionmentioning

confidence: 99%

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Investigating the Potential Use of Andrographolide as a Coadjuvant in Sickle Cell Anemia Therapy

et al. 2022

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Andrographolide is one of the main active principles of Andrographolide paniculata and has been extensively explored for its therapeutic use. Current studies focus on phytotherapeutics-based adjuvant therapy to symptomatically treat sickle cell anemia (SCA) as there is no specific drug/gene therapy available to date. The present study aimed to explore the potential of andrographolide as an adjuvant therapy for SCA in the presence or absence of hydroxyurea (HU), a key drug for SCA treatment. A panel of ex vivo and in vivo experimentations was performed to explore the antisickling activity of andrographolide, followed by evaluating pharmacokinetic and pharmacodynamic (PK/PD) activities in the presence of HU. Andrographolide showed significant antisickling activity using blood from SCA patients (ex vivo) and did not show any deleterious effect to cause hemolysis using rat blood (ex vivo). It displayed a substantial decrease in HU-induced decline in splenic lymphocyte proliferation and cytokine level (TNF-α and IFN-γ) using rat splenocytes (ex vivo). Concomitant oral administration of andrographolide with HU in rats for 15 days exhibited a noticeable improvement in the RBC count and hemoglobin levels comparable to the efficacy of l -glutamine (in vivo). Simultaneous administration of andrographolide with HU caused no marked effect on any pharmacokinetic parameters of HU except the highest plasma concentration of HU and its corresponding time point, which significantly dropped and delayed, respectively (in vivo). No considerable effect of andrographolide was observed on urease and horseradish peroxidase activity (in vitro). Overall, results suggest that andrographolide has several beneficial actions to be an adjuvant therapy to symptomatically manage SCA, but it should be avoided during the prescribed therapy of HU.

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Section: Resultssupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Investigating the Potential Use of Andrographolide as a Coadjuvant in Sickle Cell Anemia Therapy

et al. 2022

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“… 70 In addition to increased Hb F synthesis and decreased Hb S polymerization, effects include increased Hb synthesis, decreased neutrophil count, hemolysis, RBC membrane damage, endothelial cell activation and adhesion, to mention a few. 71 …”

Section: Old and New Therapiesmentioning

confidence: 99%

Management of Sickle Cell Disease Complications Beyond Acute Chest Syndrome

Ogu¹,

Badamosi²,

Camacho³

et al. 2021

JBM

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Sickle cell disease results in numerous complications that can lead to significant morbidity and mortality. Amongst them, acute chest syndrome is the leading cause of mortality. As a result, most providers are in tune with this complication and well versed with management. As sickle cell patients now live longer, they face a multitude of other complications that if left unattended, can lead to significant morbidity and mortality as well. It is critical to look beyond acute chest syndrome and adopt a more comprehensive approach to the management of the sickle cell patient.

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“…Sickle cell anemia (SCA) is an inherited disorder of blood caused by the substitution of glutamic acid by valine at the 6 th position in the β-globin chain of hemoglobin (Hb) that leads to severe pathological complications such as hemolysis, vaso-occlusion, organ damage, and death. , Hydroxyurea (HU) is the first-ever approved drug by the United States Food and Drug Administration (USFDA) for the treatment of SCA . HU mainly enhances fetal hemoglobin production to decrease the polymerization of sickle hemoglobin and hemolysis . Despite the beneficial HU effects, there are potential dose-dependent adverse effects such as myelosuppression. , Gene therapy can provide an ultimate solution for SCA, but this is not available till date.…”

Section: Introductionmentioning

confidence: 99%

“…1 HU mainly enhances fetal hemoglobin production to decrease the polymerization of sickle hemoglobin and hemolysis. 3 Despite the beneficial HU effects, there are potential dose-dependent adverse effects such as myelosuppression. 4,5 Gene therapy can provide an ultimate solution for SCA, but this is not available till date.…”

Section: Introductionmentioning

confidence: 99%

Effect of Concomitant Hydroxyurea Therapy with Rutin and Gallic Acid: Integration of Pharmacokinetic and Pharmacodynamic Approaches

et al. 2021

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Hydroxyurea (HU) is the first-ever approved drug by USFDA for sickle cell anemia (SCA). However, its treatment is associated with severe side effects like myelosuppression. Current studies are focused on the supplementation therapy for symptomatic management of SCA. In the present study, we aimed to explore rutin's and gallic acid's potential individually, for concomitant therapy with HU using pharmacokinetic and pharmacodynamic approaches since there is no such precedent till date. In vivo pharmacokinetic studies of HU in rats showed that rutin could be safely co-administered with HU, while gallic acid significantly raised the plasma concentration of HU. Both the phytochemicals did not have any marked inhibitory effect on urease but have considerable effects on horseradish peroxidase enzyme. The experimental phytoconstituents displayed a very low propensity to cause in vitro hemolysis. Gallic acid markedly enhanced the HU-induced decrease in lymphocyte proliferation. A substantial improvement by rutin or gallic acid was observed in HU-induced reduction of the main hematological parameters in rats. Combined treatment of HU with rutin and gallic acid reduced serum levels of both IL-6 and IL-17A. Overall, both rutin and gallic acid are found to have promising phytotherapy potential with HU. Further exploration needs to be done on both candidates for use as phytotherapeutics for SCA.

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Retrospection of the effect of hydroxyurea treatment in patients with sickle cell disease

Cited by 18 publications

References 68 publications

Investigating the Potential Use of Andrographolide as a Coadjuvant in Sickle Cell Anemia Therapy

Investigating the Potential Use of Andrographolide as a Coadjuvant in Sickle Cell Anemia Therapy

Management of Sickle Cell Disease Complications Beyond Acute Chest Syndrome

Effect of Concomitant Hydroxyurea Therapy with Rutin and Gallic Acid: Integration of Pharmacokinetic and Pharmacodynamic Approaches

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