Evaluating the inhibitory effect of resveratrol on the multiplication of several Babesia species and Theileria equi on in vitro cultures, and Babesia microti in mice

Shimaa Abd El-Salam El-Sayed; El-Sayed El-Alfy; Mohamed Z Sayed-Ahmed; Uday Kumar Mohanta; Saad S Alqahtani; Nawazish Alam; Sarfaraz Ahmad; Md Sajid Ali; Ikuo Igarashi; Mohamed Abdo Rizk

doi:10.3389/fphar.2023.1192999

Evaluating the inhibitory effect of resveratrol on the multiplication of several Babesia species and Theileria equi on in vitro cultures, and Babesia microti in mice

Front Pharmacol. 2023 May 30:14:1192999. doi: 10.3389/fphar.2023.1192999. eCollection 2023.

Authors

Affiliations

¹ National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
² Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
³ Parasitology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
⁴ Department of Clinical Pharmacy, College of Pharmacy, Jazan University, Jizan, Saudi Arabia.
⁵ Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
⁶ Department of Pharmaceutics, College of Pharmacy, Jazan University, Jizan, Saudi Arabia.
⁷ Department of Internal Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.

Abstract

Introduction: Histone post-translational modification is one of the most studied factors influencing epigenetic regulation of protozoan parasite gene expression, which is mediated by histone deacetylases (KDACs) and acetyltransferases (KATs). Objective and methods: The present study investigated the role of resveratrol (RVT) as an activator of histone deacetylases in the control of various pathogenic Babesia sp. and Theileria equi in vitro, as well as B. microti infected mice in vivo using fluorescence assay. Its role in mitigating the side effects associated with the widely used antibabesial drugs diminazene aceturate (DA) and azithromycin (AZM) has also been investigated. Results: The in vitro growth of B. bovis, B. bigemina, B. divergens, B. caballi and Theileria equi (T. equi) was significantly inhibited (P < 0.05) by RVT treatments. The estimated IC50 values revealed that RVT has the greatest inhibitory effects on B. bovis growth in vitro, with an IC50 value of 29.51 ± 2.46 µM. Reverse transcription PCR assay showed that such inhibitory activity might be attributed to resveratrol's stimulatory effect on B. bovis KDAC3 (BbKADC3) as well as its inhibitory effect on BbKATS. RVT causes a significant decrease (P < 0.05) in cardiac troponin T (cTnT) levels in heart tissue of B. microti- infected mice, thereby indicating that RVT may play a part in reducing the cardiotoxic effects of AZM. Resveratrol showed an additive effect with imidocarb dipropionate in vivo. Treatment of B. microti-infected mice with a combined 5 mg/kg RVT and 8.5 mg/kg ID resulted in an 81.55% inhibition at day 10 postinoculation (peak of parasitemia). Conclusion: Our data show that RVT is a promising antibabesial pharmacological candidate with therapeutic activities that could overcome the side effects of the currently used anti-Babesia medications.

Keywords: T. equi; azithromycin; babesia; cardiac troponin T; diminazene aceturate; imidocarb dipropionate; resveratrol.

Grants and funding

This study was supported by the Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia for funding the publication fee of this research work through project number: ISP22-11.