Raspberry Ketones Attenuate Cyclophosphamide-Induced Pulmonary Toxicity in Mice through Inhibition of Oxidative Stress and NF-ΚB Pathway

Abstract

Cyclophosphamide (CP) was found to have a potential toxic effect on lung tissues. Raspberry ketones (RKs) are natural antioxidant chemicals isolated from red raspberries (Rubus ideaus). They are commonly used for weight loss and obesity. The current study aimed to evaluate the possible protective effects of RKs against lung toxicity induced by CP. Mice were allocated into six groups: (1) control group; (2) CP group: received a single intraperitoneal dose of CP (150 mg/kg, i.p.); and (3–6) mice were pre-treated orally with different doses of RKs (25, 50, 100, and 200 mg/kg) for 14 consecutive days, respectively, before the administration of an intraperitoneal dose of CP (150 mg/kg, i.p.). Mice were then sacrificed under anesthesia, then lungs were removed for histopathological and biochemical investigations. A single dose of CP markedly altered the levels of some oxidative stress biomarkers and resulted in the fragmentation of DNA in lung homogenates. Histological examination of CP-treated mice demonstrated diffuse alveolar damage that involved apparent hyalinization of membranes, thickening of inter alveolar septa, and proliferation of type II pneumocytes. The immunohistochemical results of CP-treated mice revealed strongly positive Bax and weakly positive proliferating cell nuclear antigen (PCNA) staining reactivity of the nuclei of the lining epithelium of the bronchioles and alveoli. CP activated the cyclooxygenase-2/nuclear factor-kappa B pathway. However, pre-treatment with RKs significantly attenuated CP-evoked alterations in the previously mentioned parameters, highlighting their antioxidant, anti-inflammatory, and anti-apoptotic potential. RKs may be suggested to be a potential candidate to ameliorate CP-induced pulmonary toxicity.

The Antioxidant Carrichtera annua DC. Ethanolic Extract Counteracts Cisplatin Triggered Hepatic and Renal Toxicities

“…After fixation in 10% neutral buffered formalin, liver and kidney tissues were dehydrated with ethanol then embedded into paraffin wax blocks. Sections of approximately 5 µm were prepared then stained with hematoxylin/eosin (H&E) according to the method mentioned [ 41 ] then blindly examined for the extent of liver and kidney damage. The obtained sections were photographed by means of standard digital microscope camera (CX 41 binocular microscope, Olympus Deutschland, Hamburg, Germany).…”

“…Furthermore, immunohistochemical investigation was performed to evaluate the activity of the inflammatory and apoptosis biomarkers interleukin-1β (IL-1β) and caspase-3 respectively. Sections from liver and kidney tissues were stained with anti-IL-1β (Catalog number bs-0812R, Bioss Inc., Woburn, MA, USA) and anti-caspase 3 (Catalog number GTX30246, GeneTex, Irvine, CA, USA) after preparation according to the method described in [ 41 , 47 ]. 3,3-diaminobenzidine (Power-Stain™ 1.0 Poly HRP DAB Kit for Mouse + Rabbit, GENEMED, South San Francisco, CA, USA) was applied as a chromogen for immunoreaction visualization, as well as Mayer’s haematoxylin as a counterstaining.…”

Potentials of Raspberry Ketone as a Natural Antioxidant

“…Mohamed et al [ 64 ] aimed to investigate the possible protective effects of RK on lung toxicity induced by cyclophosphamide (CP) in mice. The mice were randomly divided into six groups: Group 1 (control group); Group 2 (received a single intraperitoneal (IP) dose of CP (150 mg/kg)); Groups 3–6 (pre-treated orally with four different doses of RK (25, 50, 100, and 200 mg/kg) for 14 days, before the IP administration of CP).…”

“…Likewise, Mohamed et al [ 64 ] also evaluated the MDA level, as a marker for damage to the lipid bilayer of cell membranes, to investigate the effect of CP on oxidative stress. As a result, the MDA level in mice with acute IP administration of CP was significantly increased (group 2, 730.25 ± 16.07 nmol/mg protein) compared with that in control group (group 1, 322.22 ± 9.89 nmol/mg protein).…”

An ADH toolbox for raspberry ketone production from natural resources via a biocatalytic cascade

“…In addition, raspberry ketone is utilized as an attractant in insect baits (Perez 1983 ; Metcalf et al 1983 ; Deifel 1989 ) and as a component in perfumes (Dumont et al 1996 ; Farwick et al 2019 ), whereas further applications in cosmetic industry, e.g., as skin whitening or hair growth inducing agent, remain controversial (Harada et al 2008 ; Kim et al 2016 ). Other publications promote dose-dependent health benefits with regard to an anti-obese effect (Morimoto et al 2005 ; Park 2015 ; Tsai et al 2017 ; Zhao et al 2019 ; Mir et al 2019 ) or suggest medical applications due to its anti-oxidant and anti-inflammatory potential (Parmar and Tripathi 1991 ; Khan et al 2018 ; Fouad et al 2019 ; Mohamed et al 2020 ; Hamdy et al 2020 ).…”