Hepatoprotective potential of diosmin against hepatotoxic effect of isoniazid and rifampin in wistar rats

Abstract

Objective The treatment of tuberculosis with isoniazid and rifampin is associated with hepatocellular damage. Therefore, the study was designed to evaluate the hepatoprotective potential of diosmin against hepatotoxic effect of isoniazid and rifampin in Wistar rats. Methods Hepatotoxicity was induced by administering isoniazid and rifampin (100 mg/kg), whereas diosmin was given as treatment control. Markers of liver function (ALT, AST, ALP and bilirubin), inflammatory cytokines (TNFα, IL-6 and IL-1β), apoptosis (caspase-3), oxidative stress parameters (LPO, GSH, CAT and SOD) and histological changes in liver were assessed in normal, hepatotoxic control and treatment groups. Results The administration of isoniazid and rifampin significantly increased markers of liver dysfunction (ALT, AST, ALP and bilirubin), cytokines (TNFα, IL-6 and IL-1β) and apoptosis (caspase-3). However, daily dosing of diosmin significantly reduced these markers of liver dysfunction, inflammatory cytokines and apoptosis to near normal levels. Additionally, markers of hepatocellular oxidative stress parameters were significantly altered as evident from increased LPO level and decreased endogenous antioxidants such as GSH, SOD and CAT in isoniazid-and rifampin-treated hepatotoxic group. It was observed that diosmin treatment reduced high levels of LPO and demonstrated significant improvement in antioxidant levels. Histological studies of liver also supported our biochemical findings, which are also manifested as diosmin treatment exhibited protection against hepatocellular degeneration and inflammation. Conclusion Results of the present study demonstrate hepatoprotective potential of diosmin against isoniazid-and rifampin-treated hepatotoxicity. Thus, we conclude that diosmin may be used along with anti-tubercular drugs (isoniazid and rifampin) in tuberculosis patients to overcome their hepatotoxic adverse effect.

Robust anti-tubercular profile of Solanum virginianum extract in enhancing isoniazid bioavailability and curtailing stress tolerance in Mycobacterium smegmatis

“…Anti-tubercular medications are known to cause increased levels of crucial enzymes, including alkaline phosphatase (ALP), serum glutamic oxaloacetic transaminase (SGOT or AST), and serum glutamic pyruvic transaminase (SGPT or ALT), which serve as indicative markers for hepatotoxicity ( González et al, 2017 ). Nonetheless, traditional medicinal plants, such as Apium graveolens , Apium paniculata , Ficus religiosa , Fumaria indica , Glycyrrhiza glabra , Syzygium aromaticum , Withania somnifera , and Tinospora cordifolia, have been historically employed for tuberculosis treatment, concurrently exhibiting hepatoprotective attributes ( Liu et al, 2008 ; Samal, 2016 ; Anwer et al, 2023 ). These plants represent abundant reservoirs of alkaloids, flavonoids, diterpenoids, tannins, lipids, sterols, etc., showcasing antimicrobial properties and protective effects on the liver ( Ansari et al, 2023 ).…”