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Protective role of Roflumilast against cadmium-induced cardiotoxicity through inhibition of oxidative stress and NF-κB signaling in rats.
Saudi Pharm J 2019; 27(5):673-681SP

Abstract

Cadmium (Cd), a potent cardiotoxic environmental heavy metal, induces oxidative stress and membrane disturbances in cardiac myocytes. Phosphodiesterase (PDEs) retards the positive inotropic effects of β-adrenoceptor activation by decreasing levels of cAMP via degradation. Hence, PDE inhibitors sensitize the heart to catecholamine and are therefore, used as positive inotropic agents. The present study was designed to probe the potential attenuating effects of the selective PDE4 inhibitor (Roflumilast, ROF), on cardiac biomarkers, lipid profile, lipid peroxidation products, antioxidant status and histology of cardiac tissues against Cd-induced cardiotoxicity in rats. Rats were randomly distributed into four different groups: group 1, served as the normal control group. Group 2, served as the toxic control group and were administered Cd (3 mg/kg, i.p.) for next 7 days. Groups 3 and 4, served as treatment groups that received Cd with concomitant oral administration of ROF doses (0.5 and 1.5 mg/kg), respectively for 7 days. Serum samples of toxic control group rats resulted in significant (P < 0.001) increase in lactate dehydrogenase (LDH), creatine phosphokinase (CPK), total cholesterol (TC), triglycerides (TG) and low density lipoproteins (LDL) levels with concomitant decrease in high density lipoproteins (HDL) levels in serum which were found reversed with both of ROF treatment groups. Cd also causes significant increased (P < 0.001) in myocardial malondialdehyde (MDA) contents while cardiac glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) enzyme activities were found decreased whereas both doses of ROF, significantly reversed these oxidative stress markers and antioxidant enzymes. Cardiotoxicity induced by Cd also resulted in enhanced expression of non-phosphorylated and phosphorylated form of NF-κB p65 and decreased expression of glutathione-S-transferase (GST) and NQO1 which were found reversed with ROF treatments, comparable to normal control group. Histopathological changes were also improved by ROF administration as compared to Cd treated rats alone. In conclusion, Roflumilast exhibited attenuating effect against Cd-induced cardiac toxicity.

Authors+Show Affiliations

Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.Department of Basic Sciences, Preparatory Year Deanship, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia. Department of Histopathology and Cytopathology, Faculty of Medical Laboratory Sciences, University of Gezira, Wad Madani, Sudan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31297022

Citation

Ansari, Mohd Nazam, et al. "Protective Role of Roflumilast Against Cadmium-induced Cardiotoxicity Through Inhibition of Oxidative Stress and NF-κB Signaling in Rats." Saudi Pharmaceutical Journal : SPJ : the Official Publication of the Saudi Pharmaceutical Society, vol. 27, no. 5, 2019, pp. 673-681.
Ansari MN, Ganaie MA, Rehman NU, et al. Protective role of Roflumilast against cadmium-induced cardiotoxicity through inhibition of oxidative stress and NF-κB signaling in rats. Saudi Pharm J. 2019;27(5):673-681.
Ansari, M. N., Ganaie, M. A., Rehman, N. U., Alharthy, K. M., Khan, T. H., Imam, F., ... Hamad, A. M. (2019). Protective role of Roflumilast against cadmium-induced cardiotoxicity through inhibition of oxidative stress and NF-κB signaling in rats. Saudi Pharmaceutical Journal : SPJ : the Official Publication of the Saudi Pharmaceutical Society, 27(5), pp. 673-681. doi:10.1016/j.jsps.2019.04.002.
Ansari MN, et al. Protective Role of Roflumilast Against Cadmium-induced Cardiotoxicity Through Inhibition of Oxidative Stress and NF-κB Signaling in Rats. Saudi Pharm J. 2019;27(5):673-681. PubMed PMID: 31297022.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective role of Roflumilast against cadmium-induced cardiotoxicity through inhibition of oxidative stress and NF-κB signaling in rats. AU - Ansari,Mohd Nazam, AU - Ganaie,Majid A, AU - Rehman,Najeeb Ur, AU - Alharthy,Khalid M, AU - Khan,Tajdar H, AU - Imam,Faisal, AU - Ansari,Mushtaq A, AU - Al-Harbi,Naif O, AU - Jan,Basit L, AU - Sheikh,Ishfaq A, AU - Hamad,Abubaker M, Y1 - 2019/04/02/ PY - 2019/01/15/received PY - 2019/04/01/accepted PY - 2019/7/13/entrez PY - 2019/7/13/pubmed PY - 2019/7/13/medline KW - CRF KW - Cadmium KW - Cardiotoxicity KW - GST KW - NF-κB KW - NQO1 KW - Roflumilast SP - 673 EP - 681 JF - Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society JO - Saudi Pharm J VL - 27 IS - 5 N2 - Cadmium (Cd), a potent cardiotoxic environmental heavy metal, induces oxidative stress and membrane disturbances in cardiac myocytes. Phosphodiesterase (PDEs) retards the positive inotropic effects of β-adrenoceptor activation by decreasing levels of cAMP via degradation. Hence, PDE inhibitors sensitize the heart to catecholamine and are therefore, used as positive inotropic agents. The present study was designed to probe the potential attenuating effects of the selective PDE4 inhibitor (Roflumilast, ROF), on cardiac biomarkers, lipid profile, lipid peroxidation products, antioxidant status and histology of cardiac tissues against Cd-induced cardiotoxicity in rats. Rats were randomly distributed into four different groups: group 1, served as the normal control group. Group 2, served as the toxic control group and were administered Cd (3 mg/kg, i.p.) for next 7 days. Groups 3 and 4, served as treatment groups that received Cd with concomitant oral administration of ROF doses (0.5 and 1.5 mg/kg), respectively for 7 days. Serum samples of toxic control group rats resulted in significant (P < 0.001) increase in lactate dehydrogenase (LDH), creatine phosphokinase (CPK), total cholesterol (TC), triglycerides (TG) and low density lipoproteins (LDL) levels with concomitant decrease in high density lipoproteins (HDL) levels in serum which were found reversed with both of ROF treatment groups. Cd also causes significant increased (P < 0.001) in myocardial malondialdehyde (MDA) contents while cardiac glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) enzyme activities were found decreased whereas both doses of ROF, significantly reversed these oxidative stress markers and antioxidant enzymes. Cardiotoxicity induced by Cd also resulted in enhanced expression of non-phosphorylated and phosphorylated form of NF-κB p65 and decreased expression of glutathione-S-transferase (GST) and NQO1 which were found reversed with ROF treatments, comparable to normal control group. Histopathological changes were also improved by ROF administration as compared to Cd treated rats alone. In conclusion, Roflumilast exhibited attenuating effect against Cd-induced cardiac toxicity. SN - 1319-0164 UR - https://www.unboundmedicine.com/medline/citation/31297022/Protective_role_of_Roflumilast_against_cadmium-induced_cardiotoxicity_through_inhibition_of_oxidative_stress_and_NF-κB_signaling_in_rats L2 - https://linkinghub.elsevier.com/retrieve/pii/S1319-0164(19)30052-0 DB - PRIME DP - Unbound Medicine ER -