Synergistic Power of Piceatannol and/or Vitamin D in Bleomycin-Induced Pulmonary Fibrosis In Vivo: A Preliminary Study

Nehal Ezz Eldeen; Yasser M Moustafa; Maha Abdullah Alwaili; Amani A Alrehaili; Dina M Khodeer

doi:10.3390/biomedicines11102647

Synergistic Power of Piceatannol and/or Vitamin D in Bleomycin-Induced Pulmonary Fibrosis In Vivo: A Preliminary Study

Biomedicines. 2023 Sep 27;11(10):2647. doi: 10.3390/biomedicines11102647.

Authors

Nehal Ezz Eldeen¹, Yasser M Moustafa^{1

2}, Maha Abdullah Alwaili³, Amani A Alrehaili⁴, Dina M Khodeer¹

Affiliations

¹ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
² Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt.
³ Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
⁴ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.

Abstract

Oxidative stress and epigenetic alterations, including the overexpression of all class I and II histone deacetylases (HDACs), particularly HDAC2 and HDAC4, have been identified as key molecular mechanisms driving pulmonary fibrosis. Treatment with piceatannol (PIC) or vitamin D (Vit D) has previously exhibited mitigating impacts in pulmonary fibrosis models. The present study investigated the effects of PIC, Vit D, or a combination (PIC-Vit D) on the expression of HDAC2, HDAC4, and transforming growth factor-beta (TGF-β) in the lungs; the phosphatidylinositide-3-kinase (PI3K)/AKT signaling pathway; and the antioxidant status of the lungs. The objective was to determine if the treatments had protective mechanisms against pulmonary fibrosis caused by bleomycin (BLM) in rats. Adult male albino rats were given a single intratracheal dosage of BLM (10 mg/kg) to induce pulmonary fibrosis. PIC (15 mg/kg/day, oral (p.o.)), Vit D (0.5 μg/kg/day, intraperitoneal (i.p.)), or PIC-Vit D (15 mg/kg/day, p.o. plus 0.5 μg/kg/day, i.p.) were given the day following BLM instillation and maintained for 14 days. The results showed that PIC, Vit D, and PIC-Vit D significantly improved the histopathological sections; downregulated the expression of HDAC2, HDAC4, and TGF-β in the lungs; inhibited the PI3K/AKT signaling pathway; decreased extracellular matrix (ECM) deposition including collagen type I and alpha smooth muscle actin (α-SMA); and increased the antioxidant capacity of the lungs by increasing the levels of glutathione (GSH) that had been reduced and decreasing the levels of malondialdehyde (MDA) compared with the BLM group at a p-value less than 0.05. The concomitant administration of PIC and Vit D had a synergistic impact that was greater than the impact of monotherapy with either PIC or Vit D. PIC, Vit D, and PIC-Vit D exhibited a notable protective effect through their antioxidant effects, modulation of the expression of HDAC2, HDAC4, and TGF-β in the lungs, and suppression of the PI3K/AKT signaling pathway.

Keywords: HDAC2; HDAC4; PI3K/AKT; TGF-β; bleomycin; oxidative stress; piceatannol; pulmonary fibrosis; vitamin D.

Grants and funding

This research received no external funding.