Cytoprotective Antioxidant, Anti-Inflammatory, and Antifibrotic Impact of Celery Seed Oil and Manuka Honey Against Cyclophosphamide-Induced Cystitis in Rabbits

Ayman M Mousa; Khaled S Allemailem; Fahad A Alhumaydhi; Faris Alrumaihi; Ahmad Almatroudi; Mohammad Aljasir; Ameen S S Alwashmi; Osamah Al Rugaie; Khaled E A Soliman; Abdullah S M Aljohani; Waleed Al Abdulmonem; Ahmed A Ahmed; Arif Khan; Masood A Khan; Naif AlSuhaymi; Mahdi H Alsugoor; Wafa Abdullah Al-Megrin; Abulmaaty M Elsayed

doi:10.1155/2022/2863023

Cytoprotective Antioxidant, Anti-Inflammatory, and Antifibrotic Impact of Celery Seed Oil and Manuka Honey Against Cyclophosphamide-Induced Cystitis in Rabbits

Evid Based Complement Alternat Med. 2022 Mar 17:2022:2863023. doi: 10.1155/2022/2863023. eCollection 2022.

Authors

Ayman M Mousa^{1

2}, Khaled S Allemailem^{1

3}, Fahad A Alhumaydhi³, Faris Alrumaihi³, Ahmad Almatroudi³, Mohammad Aljasir³, Ameen S S Alwashmi³, Osamah Al Rugaie⁴, Khaled E A Soliman^{4

5}, Abdullah S M Aljohani⁶, Waleed Al Abdulmonem⁷, Ahmed A Ahmed⁸, Arif Khan¹, Masood A Khan¹, Naif AlSuhaymi⁹, Mahdi H Alsugoor⁹, Wafa Abdullah Al-Megrin¹⁰, Abulmaaty M Elsayed^{11

12}

Affiliations

¹ Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia.
² Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha 13518, Egypt.
³ Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia.
⁴ Department of Basic Medical Sciences, College of Medicine and Medical Sciences, Qassim University, Unaizah 51452, Saudi Arabia.
⁵ Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Sohag University, Sohag 82524, Egypt.
⁶ Department of Veterinary Medicine, College of Agricultural and Veterinary Medicine, Qassim University, Buraydah 51452, Saudi Arabia.
⁷ Department of Pathology, College of Medicine, Qassim University, Buraydah 51452, Saudi Arabia.
⁸ Research Center, College of Medicine, Qassim University, Buraidah 51452, Saudi Arabia.
⁹ Department of Emergency Medical Services, Faculty of Health Sciences, AlQunfudah, Umm Al-Qura University, Makkah 21912, Saudi Arabia.
¹⁰ Department of Biology, Faculty of Science, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
¹¹ Department of Anatomy and Histology, Faculty of Medicine, Mutah University, Mutah, Jordan.
¹² Department of Anatomy and Embryology, Faculty of Medicine, Benha University, Benha 13518, Egypt.

Abstract

Patients treated with cyclophosphamide (CP) usually suffer from severe hemorrhagic cystitis (HC). Our previous study exhibited that mesna + celery cotherapy partially ameliorated HC. Therefore, there is a substantial need to seek alternative regimens to get complete protection against CP-induced HC. The current study investigated the effects of mesna + celery seed oil (MCSO) or mesna + manuka honey (MMH) cotherapy against CP-induced HC in adult male rabbits. The forty rabbits were divided into four equal groups and treated for three weeks. The control group (G1) received distilled water and the second group (G2) received CP (50 mg/kg/week). The third group (G3) received CP + MCSO (CPMCSO regimen), and the fourth group (G4) received CP + MMH (CPMMH regimen). The urinary bladder (UB) specimens were processed to evaluate UB changes through histopathological, immunohistochemical, ultrastructural, and biochemical investigations. In G2, CP provoked HC features (urothelial necrosis, ulceration, and sloughing), UB fibrosis, and TNF-α immunoexpression. Besides, CP reduced the activity of antioxidant enzymes (GPx1, SOD3, and CAT) and elevated the serum levels of NF-κB, TNF-α, IL-1B, and IL-6 cytokines in G2 rabbits. In contrast, the CPMMH regimen caused significant increments of UB protection against HC in G4 rabbits compared to the partial protection by the CPMCSO regimen in G3. Therefore, our study indicated for the first time that the novel CPMMH regimen resulted in complete UB protection against CP-induced HC via combined antioxidant, anti-inflammatory, and antifibrotic properties.