Metabolites of Trichoderma harzianum re-balance T-reg/Th-17 cytokine axis in epileptic rats

Abstract

Abstract Background Recurrent seizure is synchronous neuronal network hyperexcitation. Even though many anti-epileptic drugs (AEDs) are available, but have several drawbacks, including multiple drug interactions, suboptimal response rates, significant adverse effects, and a narrow therapeutic index. Trichoderma is a biocontrol agent which maintains stress-related gene expression to adapt to unstable environmental conditions. The current study sought to delineate the ameliorative effects of metabolites of Trichoderma harzianum (T. harzianum) culture filtrate (ThCF) by assessing the functions of T regulatory cells and rebalancing oxidative stress. Methods Experimental rats were divided into control, epileptic, valproic acid-treated, and T. harzianum cultured filtrate (ThCF). Lipid peroxidation, nitric oxide, and antioxidant defense enzymes were estimated. Moreover, interleukins-6, -10, -17, tumor necrosis factor (TNF-α), and transforming growth factor (TGF-β) were estimated using ELISA kits, in addition to T-reg markers; cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and forkhead box P3 (FOXP3) were estimated by qRT-PCR. Results Data revealed that the T. harzianum cultured filtrate (ThCF) retarded the lipid oxidation rate and has antioxidant activities, as well as increased levels of GPx, CAT, and SOD. Moreover, ThCF re-balances T-reg/Th-17 cytokines, restoring the pro/anti-inflammatory cytokines and Treg markers, e.g., FOXP3 and CTLA-4, to their normal level. Conclusion Trichoderma harzianum has a potent antioxidant activity with high capacity to scavenge ROS and downregulate all T-reg markers. Therefore, the present data are directed toward the characterization of new active constituents of secondary metabolites of T. harzianum with significant therapeutic functions in several diseases. The promising findings may suggest more clinical and experimental scenarios to reduce AED’s drawbacks and side effects.

Keywords

• Epilepsy
• Trichoderma harzianum
• Lipid peroxidation
• Antioxidants
• T-regulatory cells