Abstract:This study evaluates the hepatoprotective effect of carotenoids against isoniazid (INH) and rifampicin (RIF). Thirty-six adult rats were divided into the following 4 groups: (1) control group treated with normal saline; (2) INH + RIF group treated with 50 mg·(kg body mass)-1·day-1 of INH and RIF each; (3) INH + RIF+ carotenoids group treated with 50 mg·(kg body mass)-1·day-1 of INH and RIF each and 10 mg·(kg body mass)-1·day-1 of carotenoids; and (4) carotenoids group treated with 10 mg·(kg body mass)-1·day-1 … Show more
“…Hydrazine is the product of cytochrome P450 metabolising activity (5) and is believed to induce oxidative stress (6). One of the consequences of oxidative stress is lipid peroxidation, as established in animal models treated with anti-tuberculosis drugs such as isoniazid (7) or hydrazine (8). Another consequence, established by Chowdhury et al (9), is mitochondrial damage in hepatocytes.…”
Isoniazid is one of the most commonly used drugs to treat tuberculosis. Its administration is associated with a high incidence of hepatotoxicity. The aim of this study was to establish the protective effects of taurine against cytotoxicity induced by isoniazid and its suspected toxic metabolite hydrazine in isolated rat hepatocytes by measuring reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial depolarisation, reduced glutathione (GSH), and oxidised glutathione (GSSG). Isoniazid caused no signifi cant ROS formation in normal hepatocytes, but in glutathione-depleted cells it was considerable. Hydrazine caused ROS formation and lipid peroxidation in both intact and glutathione-depleted cells. Both isoniazid and hydrazine caused mitochondrial membrane depolarisation. Hydrazine lowered cellular GSH reserve and increased GSSG. Taurine ) effectively countered the toxic effects of isoniazid and/or hydrazine by decreasing ROS formation, lipid peroxidation, and mitochondrial damage. Taurine prevented depletion of GSH and lowered GSSG levels in hydrazine-treated cells. This study suggests that the protective effects of taurine against isoniazid and its intermediary metabolite hydrazine cytotoxicity in rat hepatocytes could be attributed to antioxidative action.
“…Hydrazine is the product of cytochrome P450 metabolising activity (5) and is believed to induce oxidative stress (6). One of the consequences of oxidative stress is lipid peroxidation, as established in animal models treated with anti-tuberculosis drugs such as isoniazid (7) or hydrazine (8). Another consequence, established by Chowdhury et al (9), is mitochondrial damage in hepatocytes.…”
Isoniazid is one of the most commonly used drugs to treat tuberculosis. Its administration is associated with a high incidence of hepatotoxicity. The aim of this study was to establish the protective effects of taurine against cytotoxicity induced by isoniazid and its suspected toxic metabolite hydrazine in isolated rat hepatocytes by measuring reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial depolarisation, reduced glutathione (GSH), and oxidised glutathione (GSSG). Isoniazid caused no signifi cant ROS formation in normal hepatocytes, but in glutathione-depleted cells it was considerable. Hydrazine caused ROS formation and lipid peroxidation in both intact and glutathione-depleted cells. Both isoniazid and hydrazine caused mitochondrial membrane depolarisation. Hydrazine lowered cellular GSH reserve and increased GSSG. Taurine ) effectively countered the toxic effects of isoniazid and/or hydrazine by decreasing ROS formation, lipid peroxidation, and mitochondrial damage. Taurine prevented depletion of GSH and lowered GSSG levels in hydrazine-treated cells. This study suggests that the protective effects of taurine against isoniazid and its intermediary metabolite hydrazine cytotoxicity in rat hepatocytes could be attributed to antioxidative action.
“…23,24) The hepato-protective properties of carotenoids and tocopherols have also been demonstrated in recent studies. 25,26) These effects were achieved when carotenoids and -tocopherols were respectively treated every single day with 10 mg for 6 weeks and 200 mg for 4 weeks per 1 kg body mass of rats. The LM-3 cultivar therefore had more potential as an antioxidant, at least in hepatocytes, than the other cultivars.…”
“…Difference in N-acetylation can be a result of variant NAT2 alleles that produce fast and slow acetylator phenotypes and has been associated with various cancers [18]. Hepatoprotection by carotenoids in ''INH-and RIF''-induced hepatic injury in rats showed partial protection [19]. Over the past 40 years, many techniques have been devised to determine the acetylator status phenotypically, but most of those techniques did not give an unequivocal characterization of the phenotype [20].…”
This study suggests that the acetylator status of TB patients can be detected by phenotypic method as efficaciously as by genotypic method. Therefore, phenotypic method can replace genotypic method to determine acetylating status as phenotypic method is simple and inexpensive.
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