en عمومى General پژوهشي Research <strong>Background: </strong>Recently, advances have emerged in medicine and pharmacotherapeutics, providing novel treatments for tuberculosis (TB). It is noteworthy that long-term drug consumption for TB treatment often leads to hepatotoxicity, which can have serious or even fatal side effects. Thus, many studies have focused on the assessment of the hepatoprotective effects of betaine, a glycine derivative. This study aimed at evaluating the effects of betaine to explore the underlying biochemical mechanisms of hepatotoxicity in rats, using combined isoniazid (INH) and rifampicin (RMP).<br> <strong>Methods: </strong>We used an animal model to induce hepatotoxicity with combined INH-RMP and to determine the protective effects of betaine at three doses of 125, 250 and 500 mg/kg.<br> <strong>Results:</strong> Treatment with INH and RMP led to a significant upregulation of hepatic damage markers, along with marked alteration in the histopathological lesions. The results after the use of betaine were found to be satisfactory at 500 mg/kg comparable to silymarin (200mg/kg). The hepatotoxicity was also found to be associated with generation of reactive oxygen species (ROS) and oxidative stress, indicating the deterioration of the antioxidant defense system in the liver. However, pretreatment with betaine seemed to ameliorate the INH-RMP-induced hepatotoxicity, along with marked down-regulation of oxidative stress and hepatotoxicity markers.<br> <strong>Conclusion: </strong>The study findings indicated that treatment with betaine may help alleviate the INH-RMP-induced liver pathology. This was evident by the reduced inflammation and oxidative stress via mitochondrial GSH regeneration, ROS inhibition, and protection of mitochondria complex II. Further studies are warranted to investigate the validity of these outcomes. Tuberculosis, hepatotoxicity, hepatoprotection, betaine, Oxidative stress, Reactive oxygen species. 61 69 http://ijt.arakmu.ac.ir/browse.php?a_code=A-10-1118-1&slc_lang=en&sid=1 Preena John preenajohn123@gmail.com 100319475328460015152 0009-0005-8297-5139 No Department of Pharmacology, SVKM’S Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, 400 056, India Nirav Bhatia niravbhatia1989@gmail.com 100319475328460015153 100319475328460015153 No Department of Pharmacology, SVKM’S Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, 400 056, India Pravin Kale pravinpkale@gmail.com 100319475328460015154 100319475328460015154 No Department of Pharmacology, SVKM’S Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, 400 056, India Gaurav Doshi gaurav.pharmacology@gmail.com 100319475328460015155 100319475328460015155 Yes Department of Pharmacology, SVKM’S Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, 400 056, India