Biochemical Evaluation of Some Natural Products against Toxicity Induced By Anti-tubercular Drugs in Rats

Tuberculosis (TB) is a communicative disease caused by Mycobacterium tuberculosis bacteria that may cause death if it is left untreated. WHO (2010) recommended standard drugs as first line anti-tuberculosis (anti-TB) therapy involved (HRZE): isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) received as a fixed dose combination suspension according to the body weight. However, hepatic and renal toxicity are the most serious adverse effects of these drugs. Therefore, In vitro antioxidant studies were carried out include: antiradical activity by 1,1-Diphenyl-2-picrylhydrazyl (DPPH) assay, ferric reducing antioxidant power (FRAP) and metal chelating activity. Furthermore, this study aimed to evaluate the protective effects of the hydroethanolic extract of Mentha peprita, Origanum vulgare and Pimpinella anisum against toxicity induced during treatment with combinations of anti-tuberculosis drugs compared with silymarin in rats. In vitro study revealed that all the tested extracts considered as a good source of natural antioxidants due to their high content of phenolic and flavonoid compounds and thus exhibited good antioxidant potential that decreased in the order of M. peprita > O. vulgare > P. anisum. In vivo study using a total of 56 female Sprague-Dawely rats divided into seven groups (8 rats each) as follows: Group 1 served as a normal control for 30 days; Group 2 received a combined suspension of anti-TB drugs (HRZE) in a fixed dose of 6.75, 13.5, 36.0 and 24.8 mg/Kg b.w/day, p.o., respectively for 30 days. Group 3-7 received a sole dose of M. peprita, O. vulgare or P. anisum extract or a combined polyherbal extract or silymarin (100 mg/kg b.w/day, p.o) 30 min prior to anti-TB drugs for the same period. The results demonstrated that administration of a combined anti-TB drugs induced hepatotoxicity as evidenced from a significant elevation in the serum enzyme activities [alanine amino transferase (ALT), aspartate amino transferase (AST) and alkaline phosphatase (ALP)], total bilirubin (T. Bil) and decrease in total protein (T.P), associated with renal disorder as confirmed from a market elevation in serum urea, creatinine and uric acid as well as oxidative stress confirmed from a significant decrease in total antioxidant capacity (TAC) and reduced glutathione (GSH) along with marked elevation in both markers of lipid peroxidation [malondialdehyde (MDA), Conjugated dienes (CD) and total hydroperoxides (ROOHs)], protein oxidation (protein carbonyl, PC) and DNA fragmentation. However, co-adminstration of the tested extracts with anti-TB drugs showed good hepatorenal-protection as evidence from maintenance of the aforementioned biochemical changes near normal. This improvement was decreased in the order of silymarin ~ polyherbal preparation > M. peprita > O. vulgare > P. anisum may be due to their high content of phenolic and flavonoids which might offer hepato-renal protection. This study revealed the synergistic effect of the hydroethanolic extract of Mentha peprita, Origanum vulgare and Pimpinella anisum to protect the liver and kidney tissues against toxicity induced during treatment with combined anti-TB drugs through increasing antioxidant defence capacity. In conclusion: These tested extracts may be used as a dietary supplement in polyherbal preparation by patients taking anti-tuberculosis medications. Further studies will be needed in different animal model with different doses to delineate the precise mechanisms underlying the effects of this polyherbal preparation. [Zeinab Yousef Ali. Biochemical evaluation of Some Natural Products against Toxicity Induced by Antitubercular Drugs in Rats. N Y Sci J 2012;5(10):69-80]. (ISSN: 1554-0200). http://www.sciencepub.net/newyork. 12