Abstract
Objective: Rifampicin (RIF) could be a recognized therapeutic and preventive agent against tuberculosis. Still, high rates of many side effects and symptoms related to hepatotoxicity have identified during treatment. So, the current study was aimed to evaluate the antioxidant and hepatoprotective activity of methanolic extract of Annona Squamosa Linn (MEAS) and N-Acetyl Cysteine (NAC) against RIF induced hepatic injury in male rats.
 Methods: The hepatoprotective effects of MEAS (500 mg/kg b.wt.) and NAC (100 mg/kg b.wt.) or co-treatment were assessed in a model of hepatotoxicity by RIF (300 mg/kg b. wt.) in male rats daily for 21 d. Moreover, bilirubin, total protein, albumin, ALT, AST, ALP, GGT, MDA, and GSH were estimated. In addition, the levels of IL-6, IL-10, 8(OH)dG, and Bcl2 were evaluated.
 Results: The oral administration of MEAS and NAC or their combination resulted in significant reductions in the levels of bilirubin, albumin, hepato-specific markers namely ALT, AST, ALP, GGT, and MDA as compared to the RIF group. Furthermore, MEAS and NAC or the combination of MEAS and NAC treatment significantly up-regulated the levels of total protein, glutathione reductase with concomitant decrease in inflammatory marker level IL-6 and apoptotic marker level 8(OH)dG as well as increment the level of anti-inflammatory marker IL-10 and anti-apoptotic marker Bcl2 as compared to the RIF group. Histological examination of the liver tissue indicated that co-treatment with MEAS and NAC completely abolished the inflammation and degeneration in hepatocytes and restore the liver tissue to its normal structure.
 Conclusion: The present findings demonstrated that a co-treatment of MEAS and NAC seems to be more productive and curative than alone MEAS or NAC treatment and strongly compensated the liver damage induced by RIF.
Highlights
Tuberculosis (TB) remains one of the fatal infectious diseases triggered by bacillus mycobacteria, mainly Mycobacterium tuberculosis
It is a source of enzymes capable of transforming foreign molecules. It metabolizes and detoxifies various endogenous and exogenous compounds [30]. In view of this idea, the present study showed that rats treated with anti-tubercular drug RIF recorded a dose-dependent, significant (p
The disaggregation of polyribosomal profiles induced by antituberculosis drugs is associated with the inhibition of protein synthesis, which may be parallelly responsible for the fatty liver, it contributes to disabling of the cell [36]
Summary
Tuberculosis (TB) remains one of the fatal infectious diseases triggered by bacillus mycobacteria, mainly Mycobacterium tuberculosis. It proceeds to be a major global health problem, responsible for ill-health among millions of people each year. Drug-induced hepatotoxicity continues to be a great problem in the management of TB [4]. It is the main cause of disruption during a tuberculosis treatment course and may lead to hospitalization or life-threatening events [3, 5]. It has been recognized that oxidative stress remains one of the mechanisms for Isoniazid (INZ) and RIF initiated hepatic injury [6]. Reactive oxygen species (ROS) strengthened RIF-INZ-induced hepatotoxicity, cardiovascular diseases, cancer, inflammatory diseases, autoimmune diseases (diabetes), neurodegenerative diseases, and aging decline [7]
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