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Diacerein modulates TLR4/ NF-κB/IL-1β and TRPC1/CHOP signalling pathways in gentamicin-induced parotid toxicity in rats |
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| Authors: | Dalia Mohamed Ali Mohamed H Mahmoud Rehab Ahmed Rifaai Michael Atef Fawzy Medhat Atta Nermeen N Welson Gaber El-Saber Batiha Athanasios Alexiou Marios Papadakis Walaa Yehia Abdelzaher |
| Institution: | 1. Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Minia University, Minia, Egypt
Contribution: Investigation (equal), Methodology (equal);2. Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia Contribution: Funding acquisition (equal);3. Department of Histology and Cell Biology, Faculty of Medicine, Minia University, Minia, Egypt Contribution: Methodology (equal), Resources (equal);4. Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia, Egypt Contribution: Data curation (lead), Investigation (equal), Methodology (equal);5. Department of Anatomy, Faculty of Medicine, Minia University, Minia, Egypt Contribution: Investigation (equal), Methodology (equal);6. Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Beni-Suef University, Beni Suef, Egypt;7. Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt Contribution: Funding acquisition (equal), Project administration (lead);8. Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, New South Wales, Australia;9. Department of History of Medicine, School of Medicine, University of Ioannina, Ioannina, Greece;10. Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt |
| Abstract: | The present study aimed to identify the possible protective effect of diacerein (DIA) on gentamicin (GNT)-induced parotid toxicity in rats. DIA was administered in the presence and absence of GNT. Thirty-two Wistar adult male rats were randomly arranged into four groups: control, DIA (50 mg/kg/day), GNT (100 mg/kg) and GNT+DIA groups for 8 days. Parotid oxidative stress parameters, besides inflammatory and apoptotic biomarkers, were evaluated. Salivary flow rate, transient receptor potential canonical 1 (TRCP1), and C/EBP homologous protein (CHOP) in parotid tissue were measured. A parotid histopathological examination and an interleukin-1 beta (IL-1β) immunohistochemical study were also performed. GNT significantly increased parotid oxidative stress, inflammatory, apoptotic and CHOP biomarkers with decreased salivary flow rate and TRCP1 level. A histopathological picture of parotid damage and high IL-1β immunoexpression were detected. DIA significantly normalized the distributed oxidative, inflammatory and apoptotic indicators, CHOP and TRCP1, with a prompt improvement in the histopathological picture and a decrease in IL-1β immunoexpression. These results reported that DIA protects against GNT-induced parotid toxicity via modulation of TLR4/NF-κB/IL-1β and TRPC1/CHOP signalling pathways. |
| Keywords: | diacerein gentamicin parotid toxicity rats |