Canadian journal of physiology and pharmacology | 2021
Quercetin Modulates Nrf2 and NF-κB/TLR-4 Pathways to Protect against Isoniazid and Rifampicin Induced Hepatotoxicity in vivo.
Abstract
Isoniazid and rifampicin are crucial for treating tuberculosis (TB); however, they can cause severe hepatotoxicity leading to liver failure. Therapeutic options are limited and ineffective. We hypothesized that prophylaxis with quercetin attenuates isoniazid and rifampicin induced liver injury. We randomly divided Wistar rats into seven groups (n=6). The animals received isoniazid and rifampicin or were co-treated with quercetin or silymarin for 28 days. The protective effect of quercetin was assessed using liver function tests and liver histology. NRF2 and NF-κB pathways were explored to elucidate the mechanism of action. Quercetin co-administration prevented the elevation of ALT, AST, ALP and bilirubin compared to isoniazid and rifampicin treatment alone. In the histological analysis, we observed that quercetin prophylaxis lessened the severity of hepatic necrosis and inflammation compared to the anti-TB drug treated group. Quercetin attenuated anti-TB drug induced oxidative stress by increasing NRF2 activation and expression, boosting endogenous antioxidant levels. Additionally, quercetin blocked inflammatory mediators HMGB-1 and IFN-γ, inhibiting activation of the NF-κB/TLR-4 axis. Quercetin protects against anti-TB liver injury by activating NRF2 and blocking NF-κB/TLR-4.