Effects of a new 1,2,3-thiadiazole containing hydrazone antimycobacterial agent on serum and liver biochemical parameters in female mice
- 9 September 2019
- journal article
- research article
- Published by Taylor & Francis Ltd in Drug and Chemical Toxicology
- Vol. 45 (1), 113-119
- https://doi.org/10.1080/01480545.2019.1660671
Abstract
Isoniazid (INH), a first-line drug in anti-tuberculosis therapy, is known to be potentially harmful and is associated with numerous side effects especially in the blood and liver. In the course of our previous investigations, 1,2,3-thiadiazole containing hydrazone (compound 3) showed excellent antimycobacterial activity against a referent strain M. tuberculosis H37Rv (MIC value 0.39 μM), low cytotoxicity, and did not have toxic effects when administered by oral or intraperitoneal routes to experimental animals (selectivity index SI > 1979, LD50>2000 mg/kg b.w.) what revealed its suitability for further exploration. In the present study compound 3 was chosen to determine its effects on the liver and kidney functions in female mice. The compound was administered orally for 14 days at three doses (100, 200, and 400 mg/kg b.w.). The quantity of malondialdehyde (MDA), the level of reduced glutathione (GSH), blood hematological and biochemical parameters were assessed, and urine analysis was carried out. As a positive control INH was used orally at a dose of 50 mg/kg b.w. The investigated compound 3 did not affect the urine and serum hematological and biochemical parameters as INH did, compared to those of the control mice. The new compound did not affect significantly the MDA quantity and maintained its level near to the control values, though lower by 36% (p < 0.05) than in the INH treated animals. At the higher doses, 200 and 400 mg/kg, it depleted the GSH content by 25% (p < 0.05), compared to the control. However, its level remained 47% (p < 0.05) higher than in the INH treated animals.Keywords
Funding Information
- Medical Science Council, MU-Sofia, Bulgaria (77/03.05.2018)
This publication has 36 references indexed in Scilit:
- New indole and indazole derivatives as potential antimycobacterial agentsMedicinal Chemistry Research, 2019
- Quinolone-isoniazid hybrids: synthesis and preliminary in vitro cytotoxicity and anti-tuberculosis evaluationMedChemComm, 2019
- Ameliorative Effect of Rutin Against Isoniazid-induced Alterations in Certain Hematological and Biochemical Parameters of Albino RatsInternational Journal of Pharmacology, 2017
- Synthesis, antimycobacterial activity and docking study of 2-aroyl-[1]benzopyrano[4,3- c ]pyrazol-4(1 H )-one derivatives and related hydrazide-hydrazonesBioorganic & Medicinal Chemistry Letters, 2017
- Antimycobacterial activity of novel hydrazide-hydrazone derivatives with 2 H -chromene and coumarin scaffoldBioorganic & Medicinal Chemistry Letters, 2017
- Mechanisms of isoniazid‐induced idiosyncratic liver injury: Emerging role of mitochondrial stressJournal of Gastroenterology and Hepatology, 2014
- Isoniazid suppresses antioxidant response element activities and impairs adipogenesis in mouse and human preadipocytesToxicology and Applied Pharmacology, 2013
- The protective effects of ursodeoxycholic acid on isoniazid plus rifampicin induced liver injury in miceEuropean Journal of Pharmacology, 2011
- Activity of a new class of isonicotinoylhydrazones used alone and in combination with isoniazid, rifampicin, ethambutol, para-aminosalicylic acid and clofazimine against Mycobacterium tuberculosisJournal of Antimicrobial Chemotherapy, 2002
- Isoniazid – and rifampicin–induced oxidative hepatic injury – protection by N–acetylcysteineHuman & Experimental Toxicology, 2000