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allied
academies
Joint Event on
S e p t e m b e r 1 0 - 1 1 , 2 0 1 8 | D u b l i n , I r e l a n d
TOXICOLOGY AND PHARMACOLOGY
PHARMACEUTICAL CHEMISTRY & DRUG DISCOVERY
&
Global Congress on
International Conference on
Pharma Chem Congress 2018 & Toxicology Congress 2018
Asian Journal of Biomedical and Pharmaceutical Sciences
|
Volume 8
Asian J Biomed Pharmaceut Sci 2018, Volume 8 | DOI: 10.4066/2249-622X-C2-006
MITIGATION OF DRUG-INDUCED HEPATOTOXICITY BY NOVEL PHENOLIC
ACID-ISONIAZID MUTUAL PRODRUGS: DESIGN, SYNTHESIS, KINETICS
AND BIO EVALUATION
Suneela Dhaneshwar
Amity University, Uttar Pradesh, India
Aims & Objective: To overcome hepatotoxicity caused by long term use of anti-tubercular agent isoniazid (INH), a novel hepato-
protective prodrug strategy was developed by combining INH with phenolic acids as antioxidant carriers for probable synergistic
effect.
Methodology: INH was conjugated with antioxidant phenolic acids through a bioreversible amide linkage using Schotten Bau-
mann technique. Synthesized prodrugs were characterized by spectral analysis and
in vitro
release kinetics was studied by HPLC.
Hepatoprotective potential was evaluated in male Wistar rats by performing the liver function tests, oxidative stress markers and
histopathology studies.
Results: Prodrugs resisted hydrolysis in acidic (pH 1.2), basic (pH 7.4) buffers and rat stomach homogenates whereas hydrolyzed
significantly (56.03-88.62%) in intestinal homogenates over a period of 6h. All the prodrugs were effective in abating oxidative
stress and re-establishing the normal hepatic physiology. Especially the effect of prodrugs of INH with gallic acid and syringic
acid in restoring the levels of enzymes superoxide dismutase and glutathione peroxidase and abrogating liver damage was note-
worthy.
Conclusion: The findings of this investigation demonstrated that the reported mutual prodrugs can add safety and efficacy to
future clinical protocols of tuberculosis treatment.