Cardiovascular & Hematological Agents in Medicinal Chemistry - Volume 21, Issue 1, 2023

Radiation-induced heart disease (RIHD) is a significant cause of morbidity in breast and other mediastinal cancers. The many molecular and cellular patho-mechanisms that have a role in RIHD are not completely understood. Endothelial injury, oxidative stress, and inflammation, as well as endoplasmic reticulum and mitochondrial damage, are considered the primary causes of RIHD. Ferroptosis is a newly discovered type of cell death that results from irondependent lipid peroxide accumulation. As ferroptosis plays an important role in the pathogenesis of cardiovascular diseases, it seems that it has a significant effect on RIHD. It was recently shown that ionizing radiation (IR) generates severe ferroptosis, which is a critical component of Radiotherapy-mediated normal cell toxicity. These findings support the use of a ferroptosis inhibitor to reduce RIHD. In this perspective review, we summarize the role of ferroptosis in pathogens of cardiovascular disease and radiation toxicity, and we will introduce ferroptosis inhibitors as a new strategy to prevent or reduce RIHD.

Diabetic patients with chronic kidney disease have a high risk of developing cardiovascular disease-related mortality and morbidity compared to non-diabetic chronic kidney disease patients. The Majority of chronic kidney disease patients with diabetes remain undiagnosed and have a higher incidence of cardiovascular comorbidities even when they do not progress to endstage renal failure. Both traditional cardiovascular risk factors and non-traditional cardiovascular risk factors are known to be present in a higher magnitude in diabetic patients with chronic kidney disease and are known to partially account for the increased incidence of cardiovascular disease compared to non-diabetic chronic kidney disease patients. Moreover, there is no definitive evidence for potential therapeutic treatment options for cardiovascular disease among diabetic patients with chronic kidney disease, as these patients have often not been included in major cardiovascular trials. Therefore, there is a need to recognize diabetic patients with chronic kidney disease patients having a high cardiovascular disease risk for definite and immediate medical attention at an individual patient level. Increased awareness, timely diagnosis, and intervention with respect to control these plays a pivotal role in avoiding undesirable cardiovascular disease events and lead to improved treatment outcomes among these patients. Further research is warranted to understand the risk factors for cardiovascular disease and to develop and implement preventive and treatment strategies to decrease the high morbidity and mortality among diabetic patients with chronic kidney disease. This review summarizes the available epidemiological data, and risk factors, discusses clinical presentations, and suggests prevention and management strategies for cardiovascular disease risk among diabetic patients with chronic kidney disease.

Aims: The goal of this work was to evaluate the antihypertensive activity of Prunus armeniaca. Background: Prunus armeniaca is known for its beneficial medicinal properties. Objective: This study aimed to evaluate the effect of the aqueous extract of Prunus armeniaca L. (P. armeniaca) leaves (PAAE) on arterial blood pressure in normotensive and hypertensive rats. Materials and Methods: In the in vivo examination, N-omega-Nitro-L-arginine methyl ester hydrochloride( L-NAME)-induced hypertensive and normotensive rats received PAAE (160 and 100 mg/kg) orally for the acute experiment spanning 6 hours and for seven days for the subchronic treatment; their blood pressure parameters were also evaluated. In the in vitro experiment, isolated intact thoracic aortic rings were precontracted with KCl (80 mM) and epinephrine (EP) (10 μM), and vascular dilatation was assessed. Results: PAAE lowered blood pressure parameters in L-NAME-induced hypertensive without affecting normotensive rats following oral administration, suggesting that PAAE possesses an antihypertensive effect. In addition, PAAE (0.25-1 mg/mL) revealed a vasorelaxant effect in thoracic aortic rings precontracted by EP (10 μM), and this effect was especially reduced in the presence of glibenclamide or nifedipine. However, PAAE (0.25-1 mg/mL) had only a minimal vasorelaxant effect on thoracic aortic rings precontracted by KCl (80 mM). Conclusion: The results demonstrate that the P. armeniaca aqueous extract possesses potent antihypertensive and vasorelaxant activity, and its vasorelaxant activity seems to be mediated through the opening of ATP-sensitive K+ channels and inhibition of L-type calcium channels.

Aim: This study investigates the prevalence of non-malignant lesions of the cervix among various biopsy samples. Methods: This case study consists of 50 cases of cervical biopsy over almost two years. The case history and clinical details of the patients were obtained. Results: 60% of the cases that participated in this study reported white discharge per vaginum as a common clinical symptom. 4 cases (8%) showed koilocytic changes specific to the human papillomavirus during the study. Only 2% of the non-specific cervicitis showed lymphoid aggregates. Endocervical changes projected papillary endocervicitis with 9 cases (18%), squamous metaplasia with 7 cases (14%), and nabothian follicle cyst with 3 cases (6%). Conclusion: It has been concluded that 50 cases were studied histologically, which had adequate representation of both ecto and endocervical tissue. Moreover, 31-40 years of age of patients showed the highest percentage of non-neoplastic lesions of the cervix when compared to other age groups.

Aims: The study aimed to study the antihypertensive activity of Laurus nobilis. Background: Laurus nobilis L. is used to treat hypertension in Morocco. Objective: The study was designed to investigate the effect of the aqueous extract leaves of Laurus nobilis (AELN) on blood pressure. Materials and Methods: The antihypertensive and vasorelaxant activities of AELN were pharmacologically investigated in normotensive and L-NAME-induced hypertensive rats. Thereafter, blood pressure was evaluated, and the ex-vivo vasorelaxant activity of this extract was performed. Results: A considerable decrease in blood pressure parameters were observed in L-NAMEinduced hypertensive rats treated with AELN. The extract induced a vasorelaxant effect on the aorta precontracted with epinephrine or KCl by inhibiting extracellular Ca2+ entry. Conclusion: The study demonstrates that Laurus nobilis aqueous extract exhibits potent antihypertensive and vasorelaxant activities via inhibiting Ca²⁺ entry.

Background: There are several controversies regarding the association between serum magnesium depletion and microalbuminuria in type 2 diabetic patients. Objective: Therefore, this study aimed to assess serum magnesium concentrations in Type 2 diabetic patients with microalbuminuria and normoalbuminuria in Birjand, Iran, in 2019. Methods: In this cross-sectional study, 25 type 2 diabetes patients with microalbuminuria were enrolled as the case group and 25 type 2 diabetes patients with normoalbuminuria as the control group. Both groups were matched for age, sex, hypertension, and dyslipidemia. Blood samples were obtained for serum magnesium measurement. Results: Our findings showed no significant difference between serum magnesium concentration in the case and control groups (mean serum magnesium concentration for case group: 2.34 ± 0.35 mg/dl and control group: 2.27 ± 0.33 mg/dl). Pearson correlation coefficient analysis did not show any correlation between serum magnesium levels and urine albumin levels in patients with microalbuminuria versus patients with normoalbuminuria (r = 0.06, p = 0.67). Conclusion: This study did not indicate a correlation between serum magnesium concentrations and microalbuminuria in Type 2 diabetic patients.

Background & Objective: The use of the hemoperfusion method is recommended for treating cytokine storms and reducing complications in patients with COVID-19. The side effects of this treatment are not known; therefore, this study was performed to determine the final outcome and complications of hemoperfusion in patients with COVID-19 hospitalized in ICU. Methods: In this retrospective cross-sectional study, all patients with severe COVID-19 without any comorbidities or organ failure underwent hemoperfusion treatment in ICU at Kosar Hospital in Semnan, Iran, from March to November 2021 were included. The clinical data and short-term complications up to 10 days after hemoperfusion and the final outcome were extracted from medical files. Results: The mean age of 40 patients with severe COVID-19 undergoing hemoperfusion was 57.5±15.9 years. Most (24, 60%) patients were male. The time interval from hospitalization to hemoperfusion and the time interval between hemoperfusion and final outcome was 4.85 days and 8.30 days, respectively. Arrhythmia, bleeding, thrombocytopenia, and coagulation disorders were the most common short-term complications of hemoperfusion in patients with COVID-19, respectively. Most complications occurred on the second and third days after hemoperfusion. Mortality occurred in 20 (50 %) patients with severe COVID-19 undergoing hemoperfusion in ICU. Conclusion: It seems that the short-term complications and deaths due to hemoperfusion are relatively high in patients with COVID-19 admitted to the ICU. Further studies are recommended.

Introduction: Chronic myeloid leukemia (CML) is a progressive myeloproliferative disorder resulting from forming a chimeric BCR-ABL gene. The proteins derived from this gene can affect some genes from various signaling pathways such as PI3K/AKT/Wnt/catenin/JAK/Stat involved in proliferation, differentiation, cell death, and genes related to autophagy. Imatinib is the first-line treatment for CML patients, with durable and proper responses in Iranian children and adult CML patients. Hence, we aimed to evaluate the mRNA expression of some selected key genes from those pathways in patients with CML before and under treatment. Methods: In the case-control study, the mRNA expression of PTEN, LEF1, JAK3, LC3 and p62 genes were measured in 51 CML patients (6 patients before treatment and 45 patients under treatment with imatinib mesylate) and 40 healthy controls using the Real-time PCR method. Results: The mRNA expression of PTEN and P62 were significantly higher in newly diagnosed patients than in controls (P<0.0001 and P = 0.0183, respectively), while the expression of the LC3 gene was significantly lower in the untreated newly diagnosed group than in control subjects (P = 0.0191). The expression level of PTEN, LEF1, JAK3 and P62 genes were significantly decreased in patients under treatment than in the group before treatment (P = 0.0172, P = 0.0002, P = 0.0047 and P = 0.0038, respectively). A positive correlation was seen between the gene expression of P62 and BCR-ABL in the patients under treatment (r 0529, P = 0.016). Conclusion: Our findings showed that the changes in expression of these genes were related to the patient’s treatment. Due to the key role of these genes in proliferation, differentiation and tumor suppression, it is proposed that these genes may be helpful for follow-up of treatment in CML patients.