Curcumin Prevents Cyclophosphamide-Induced Lung Injury in Rats by Suppressing Oxidative Stress and Apoptosis

Sultan A M Saghir,Amir M Al Hroob,Naif Al-Gabri,Hagar Y Rady,Medhat Taha,Ayman M Mahmoud,Maged A Al-Garadi,Sulaiman A Alharbi,Mahfoudh A M Abdulghani,Amer A Almaiman,Nouran K Olama,May Bin-Jumah

doi:10.3390/pr8020127

Abstract

Curcumin (CUR) has been used since ancient times to treat several ailments as it possesses many pharmacological activities. This study intended to explore the mechanism underlying the protective effects of CUR in remodeling oxidative stress and apoptotic signals in cyclophosphamide (CP)-induced pulmonary injury in albino rats. CUR was administered at a dose of 300 mg/kg/day for 7 days and on the seventh day a single dose of CP (200 mg/kg) was given. Histopathological and ultrastructural examinations of CP-intoxicated rats showed complete alveolar obstruction, thickened inter-alveolar septa, enlarged blood vessels, severe inflammatory edema with pyknotic nuclei, and disappearance of cytoplasmic organelles. Significant increases in caspase-3, malondialdehyde (MDA), and protein carbonyl (PCO) and significant decreases in superoxide dismutase (SOD) and glutathione peroxidase (GPx) were observed. In contrast, rats that received CUR showed clear and empty lumina with single row of pneumocytes, disappearance of edema, and no interstitial electron dense bodies in rats’ lung tissues. Additionally, CUR significantly reduced caspase-3, MDA, and PCO and increased SOD and GPx. In conclusion, these findings revealed the protective effects of CUR against CP-induced pulmonary injury in rats through suppressing oxidative damage and apoptosis.

Highlights

Cyclophosphamide (CP) is an antineoplastic alkylating agent extensively used for treating various malignancies, including lymphoma, leukemia, multiple myeloma, ovarian cancer, breast cancer, and sarcoma [1]
[42].changes, the potential of to prevent histological and ultrastructural changes, oxidative stress, and apoptosis provoked by CP in the lung of rats
hematoxylin and eosin (H&E) staining of the lung and tissues of the CPchanges group showed the presence staining of the lung tissues of the group showed the presence of sever obstruction of alveoli, thickened interalveolar septa, edema in the interalveolar septa, and compensatory emphysema alveoli, thickened interalveolar edema in the interalveolar septa, and compensatory combined with thickened septa. septa, This was confirmed by the ultrastructural examination of lung tissues emphysema combined with thickened septa

Summary

Introduction

Cyclophosphamide (CP) is an antineoplastic alkylating agent extensively used for treating various malignancies, including lymphoma, leukemia, multiple myeloma, ovarian cancer, breast cancer, and sarcoma [1]. Protein carbonyl (PCO), a type of oxidized protein formed as a result of reaction with ROS, plays an important role in oxidative stress processes. It can react with ROS or other molecules such as lipids and sugars to generate reactive carbonyl derivatives (RCD), which are highly reactive with protein. The metabolites 4-hydroxycyclophosphamide and acrolein have been suggested to induce direct toxic effect on lung cells These two metabolites can directly damage the lung cells through minimizing microsomal enzyme activity [14] and disturbing the antioxidant activity in lung [15,16,17]

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