Hesperidin Attenuates Hypothyroidism-Induced Lung Damage in Adult Albino Rats by Modulating Oxidative Stress, Nuclear Factor Kappa-B Pathway, Proliferating Cell Nuclear Antigen and Inflammatory Cytokines

Walaa Hegazy; Hader I Sakr; Manal Abdul Hamid; Mohamed A Abdelaziz; Marwa Salah; Eman S Abdel Rehiem; Adel Abdel Moneim

doi:10.3390/biomedicines11061570

Hesperidin Attenuates Hypothyroidism-Induced Lung Damage in Adult Albino Rats by Modulating Oxidative Stress, Nuclear Factor Kappa-B Pathway, Proliferating Cell Nuclear Antigen and Inflammatory Cytokines

Biomedicines. 2023 May 29;11(6):1570. doi: 10.3390/biomedicines11061570.

Authors

Walaa Hegazy¹, Hader I Sakr^{2

3}, Manal Abdul Hamid⁴, Mohamed A Abdelaziz^{5

6}, Marwa Salah⁴, Eman S Abdel Rehiem⁷, Adel Abdel Moneim⁷

Affiliations

¹ Histology Division, Basic Science Department, Faculty of Physical Therapy, Nahda University, Beni-Suef 62511, Egypt.
² Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
³ Department of Medical Physiology, Medicine Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia.
⁴ Cell Biology, Histology and Genetics Division, Zoology Department, Faculty of Science, Beni-Suef University, Salah Salem St., Beni-Suef 62511, Egypt.
⁵ Basic Medical Sciences Department, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
⁶ Medical Physiology Department, Faculty of Medicine, Al-Azhar University, Cairo 11651, Egypt.
⁷ Molecular Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Salah Salem St., Beni-Suef 62511, Egypt.

Abstract

The occurrence of worsening pulmonary function has been connected to hypothyroidism (HPO). Hesperidin (HES) was suggested to have antioxidant, anti-proliferative, and anti-inflammatory potential. Our study's objective was to determine whether HES could reduce carbimazole (CBZ)-induced lung injury more effectively than Eltroxin (ELT) in adult male albino rats or not. At random, 32 rats were distributed into four groups: Group I: normal control, to induce HPO, the remaining three groups were given CBZ (20 mg/kg/day) dissolved in distilled water for 1 week. They were then split up into three groups. Group II: orally administered CBZ (20 mg/kg b.w in water/day), Group III: HES (200 mg/kg/day) dissolved in 1% carboxymethyl-cellulose + CBZ treated, and Group IV: ELT (0.045 mg/kg/day) dissolved in distilled water + CBZ treated. All treatments were delivered for 12 weeks. Blood was collected to assess thyroid-stimulating hormone (TSH) and thyroid hormones (THs). Lung injury was evaluated based on the pulmonary content of interleukin (IL)-35, IL-6, and tumor necrosis factor-alpha (TNF-α), along with the estimation of lipid peroxidation, catalase, glutathione levels, superoxide dismutase, heme oxygenase-1 (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2). The histological, ultrastructural, and immunohistochemical study of nuclear factor Kappa-B (NF-κB) and inducible nitric oxide synthase (iNOS), together with estimating the proliferation of cells using Antigen Ki-67 in lung tissue were performed. HES and ELT primarily suppressed variable lung damage mechanisms by suppressing TSH, the NF-κB/TNF-α pathway, iNOS, lipid peroxidation, Ki-67, and inflammatory mediators. On the other hand, they improved THs, antioxidant parameters, and the Nrf2/HO-1 pathway. HES and ELT exhibited an ameliorative effect that was reflected in the histopathological, immunohistochemical, and ultrastructural results. These results indicate that HES is a pneumoprotective agent that could be a promising treatment for oxidative stress, inflammation, and proliferation.

Keywords: hesperidin; histopathological; hypothyroidism; immunohistochemical; inflammatory cytokines; lung injury; oxidative stress.

Grants and funding

Project number (PSAU / 2023 / R / 1444)./This study was supported via funding from Prince Sattam Bin Abdulaziz University