Effects of rosmarinic acid on cyclophosphamide-induced nephrotoxicity in rats
Öz
Purpose: Cyclophosphamide (CP) is an antineoplastic agent. It is used in the treatment of many types of cancer. Rosmarinic acid (RA) exhibits remarkable biological activities such as anti-inflammatory, antitumor, antibacterial, and antimicrobial effects. This study aimed to evaluate the effect of rosmarinic acid against CP-induced nephrotoxicity.
Materials and Methods: Eighteen male Sprague Dawley rats were randomly divided into 3 equal groups; Sham group (n=6): 0.9% saline solution/8 days/oral gavage + 0.9% saline solution/8th day/intraperitoneal, CP group (n=6): 0.9% saline solution/8 days/oral gavage + 200 mg/kg/8th day/intraperitoneal CP, and CP+RA group (n=6): 100 mg/kg/8 days/oral gavage RA + 200 mg/kg/8th day/intraperitoneal CP was applied. Hematoxylin and Eosin, Periodic Acid-Schiff, and Masson’s Trichrome staining were performed on the collected tissues
Results: Histopathological evaluation revealed tubular atrophy, glomerular damage, vascular congestion, vacuolization, and interstitial inflammation in the CP group. Histopathological scores were significantly lower in the CP+RA group compared to the CP group. Intertubular fibrosis was observed in the CP group compared to the Sham group. Fibrosis decreased with rosmarinic acid. PAS-stained sections from the CP group showed tubular epithelial vacuolization, brush border, and basal membrane disruption. These findings decreased with rosmarinic acid. The increased blood urea nitrogen level in the CP group was lower in the CP+RA group, while the decreased SOD level in the CP group was higher in the CP+RA group.
Conclusion: RA has protective effects against CP causing tubular atrophy, glomerular damage, vascular congestion, vacuolization, and interstitial inflammation in the kidney
Anahtar Kelimeler
Nephrotoxicity, Cyclophosphamide, Rat, Rosmarinic acid
Proje Numarası
TTU-2018-8011
Kaynakça
- Emadi A, Jones RJ, Brodsky RA. Cyclophosphamide and cancer: golden anniversary. Nat Rev Clin Oncol. 2009;6:638-47.
- Fraiser LH, Kanekal S, Kehrer, JP. Cyclophosphamide toxicity. Characterising and avoiding the problem. Drugs. 1991;42:781–95.
- Swamy MK, Sinniah UR, Ghasemzadeh A. Anticancer potential of rosmarinic acid and its improved production through biotechnological interventions and functional genomics. Appl Microbiol Biotechnol. 2018;102:7775-93.
- Swarup V, Ghosh J, Ghosh S, Saxena A, Basu A. Antiviral and anti-inflammatory effects of rosmarinic acid in an experimental murine model of Japanese encephalitis. Antimicrob Agents Chemother. 2007;51:3367-70.
- Ge L, Zhu M, Li X, Xu Y, Ma X, Shi R et al. Development of active rosmarinic acid-gelatin biodegradable films with antioxidant and long-term antibacterial activities. Food Hydrocoll. 2018;83:308-16.
- Laura PF, Garzón MT, Vicente M. Relationship between the antioxidant capacity and effect of rosemary (Rosmarinus officinalis L.) polyphenols on membrane phospholipid order. J Agric Food Chem. 2010;58:161-71.
- Cojocaru IM, Cojocaru M, Sapira V, Ionescu A. Evaluation of oxidative stress in patients with acute ischemic stroke. Rom J Intern Med. 2013;51:97-106.
- Ijaz MU, Mustafa S, Batool R, Naz H, Ahmed H, Anwar H. Ameliorative effect of herbacetin against cyclophosphamide-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction. Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221132140.
- Voelcker G. Causes and possibilities to circumvent cyclophosphamide toxicity. Anticancer Drugs. 2020;31:617-622.
- Ahmed RA, Alam MF, Alshahrani S, Jali AM, Qahl AM, Khalid M, et al. Capsaicin ameliorates the cyclophosphamide-induced cardiotoxicity by ınhibiting free radicals generation, inflammatory cytokines, and apoptotic pathway in rats. Life (Basel). 2023;14;13:786.
