Protective Effects of Silymarin Against Amphotericin-B-associated Nephrotoxicity in Rats: in Vivo and in Silico Studies
Oluwafemi Ezekiel Kale1,2*,Olaoluwa Temitope Talabi3, Muinat Moronke Adeyanju4 , Ambrose Oche Gorge5, Temitope Funmi Kale2, Adebola Dan Deru6,Foluke Debora Adewunmi6, Abidemi James Akindele7, Olufunsho Awodele7
- Department of Pharmacology and Therapeutics, Olabisi Onabanjo University, Ago-Iwoye, Sagamu Campus, Ogun State, Nigeria.
- Department of Pharmacology, Benjamin Carson (Snr.) School of Medicine, Babcock University, Ilishan Remo, Ogun State, Nigeria.
- Department of Biochemistry, College of Medicine, PMB 12003, Idi-Araba Campus, University of Lagos, Nigeria
- Department of Biochemistry, Olabisi Onabanjo University, Ago-Iwoye, Sagamu Campus, Ogun State, Nigeria.
- Department of Biochemistry, University of Ilorin, Ilorin, Nigeria.
- Department of Biochemistry, Benjamin Carson (Snr.) School of Medicine, Babcock University, Ilishan Remo, Ogun State, Nigeria.
- Department of Pharmacology, Therapeutics and Toxicology, College of Medicine, PMB 12003, Idi-Araba Campus, University of Lagos, Nigeria
| Key words:
Nephrotoxicity, Amphotericin, Silymarin; Wistar Rats; Molecular Docking. .
*Corresponding author: kale.oluwafemi@oouagoiwoye.edu.ng; kalefemi@gmail.com Page No.: 54-65 Volume: 2, Issue 2 2021 Trends in Natural Products Research Copy Right: NAPREG |
Abstract Amphotericin B (AmB) is a well-known antifungal drug but its use is limited by its nephrotoxicity. This study investigated the possible modulatory effect of Silymarin during AmB induced nephrotoxicity using both in vivo and in silico methods. Adult rats were divided into six groups of seven per group and assigned into the control, AmB (2.5 mg/kg, i.p.), silymarin(dose), AmB (2.5 mg/kg) plus silymarin (0.5, 1 and 2 mg/kg, p.o.) groups. Treatments lasted for seven days and all rats the were sacrificed 24 hours after the last administration. Changes in biochemical, antioxidant parameters, and kidney histopathology were assessed. Also, in silico analyses using the PyRx, and Auto DockVina exhaustive search docking function were also conducted. From the results, AmB administration produced significantly (p < 0.05) elevated serum creatinine, urea and uric acid levels by 187 %, 100.2 % and 58.4 % compared with the control group. Similarly, serum total cholesterol (TC) (80.2 %) and malondialdehyde (MDA, 145.5 %) levels were increased. Reduced glutathione (GSH) and high-density lipoprotein (HDL) levels were significantly (p < 0.05) lowered in AmB-administered rats. Silymarin treatments lowered creatinine, MDA, and increased GSH, HDL, catalase levels respectively. Silymarin significantly lowered (p < 0.05) TC levels and restored kidney damages in treated rats. Molecular docking results, indicated that silymarin had the highest binding energy of -5.2 kcal/mol and demonstrated potentials at the active site of CYS18 and HIS19 hydrogen bonds residues or PHE47, TYR68, PRO31, MET18, LYS80, ILE82, and LEU33 hydrophobic interactions. Overall, these results showed that silymarin possesses the potential to offer chemo preventive benefits against AmB-associated toxicity, although, further trials to unravel the clinical relevance will be explored. |