MyMedR

Fulltext Cytotoxic Activity of Isoniazid Derivative in Human Breast Cancer Cells

Barathan M, Zulpa AK, Vellasamy KM, Mariappan V, Shivashekaregowda NKH, Ibrahim ZA, et al.

In Vivo, 2021 8 20;35(5):2675-2685.

PMID: 34410956 DOI: 10.21873/invivo.12551

BACKGROUND/AIM: Isoniazid is an antibiotic used for the treatment of tuberculosis. Previously, we found that the isoniazid derivative (E)-N'-(2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) could be developed as novel antimycobacterial agent by lead optimization. We further explored the ability of this compound compared to zerumbone in inhibiting the growth of MCF-7 breast cancer cells.

MATERIALS AND METHODS: Cytotoxicity was measured by the MTT assay and further confirmed via apoptosis, ROS, cell cycle, DNA fragmentation and cytokine assays.

RESULTS: ITHB4 demonstrated a lower IC50 compared to zerumbone in inhibiting the proliferation of MCF-7 cells. ITHB4 showed no toxicity against normal breast and human immune cells. Apoptosis assay revealed that ITHB4, at a concentration equal to the IC50, induces apoptosis of MCF-7 cells and cell cycle arrest at the sub-G1 and G2/M phases. ITHB4 triggered accumulation of intracellular ROS and nuclear DNA fragmentation. Secretion of pro-inflammatory cytokines induced inflammation and potentially immunogenic cell death.

CONCLUSION: ITHB4 has almost similar chemotherapeutic properties as zerumbone in inhibiting MCF-7 growth, and hence provide the basis for further experiments in animal models.

Matched MeSH terms: Isoniazid/therapeutic use

Lupus vulgaris in an immunocompromised patient

Jalalonmuhali M, Lee YY, Lee CK, Ismail R, Chandran PA

Int J Dermatol, 2014 Feb;53(2):234-7.

PMID: 22913324 DOI: 10.1111/j.1365-4632.2012.05463.x

Matched MeSH terms: Isoniazid/therapeutic use

Novel compounds targeting InhA for TB therapy

AlMatar M, Makky EA, Var I, Kayar B, Köksal F

Pharmacol Rep, 2018 Apr;70(2):217-226.

PMID: 29475004 DOI: 10.1016/j.pharep.2017.09.001

Tuberculosis (TB) is described as lethal disease in the world. Resistant to TB drugs is the main reason to have unfavourable outcomes in the treatment of TB. Therefore, new agents to replace existing drugs are urgently needed. Previous reports suggested that InhA inhibitors, an enoyl-ACP-reductase, might provide auspicious candidates which can be developed into novel antitubercular agents. In this review, we explain the role of InhA in the resistance of isoniazid. Furthermore, five classes of InhA inhibitors, which display novel binding modes and deliver evidence of their prosperous target engagement, have been debated.

Matched MeSH terms: Isoniazid/therapeutic use

A thiacetazone toxicity trial in Sarawak

Webb AH

N Z Med J, 1973 Nov 14;78(502):490-12.

PMID: 4129254

Matched MeSH terms: Isoniazid/therapeutic use

Isoniazid preventive therapy in correctional facilities: a systematic review

Al-Darraji HA, Kamarulzaman A, Altice FL

Int J Tuberc Lung Dis, 2012 Jul;16(7):871-9.

PMID: 22410101 DOI: 10.5588/ijtld.11.0447

Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide and the main cause of death in correctional facilities in middle- and low-income countries. Due to the closed environment and the concentration of individuals with TB-related risk factors, effective measures are required to control TB in such settings. Isoniazid preventive therapy (IPT) represents an effective and cost-effective measure. Despite international recommendations that IPT be integral to TB control, it is seldom deployed. A systematic review of interventions used to assess IPT initiation and completion in correctional facilities was conducted using published studies from two biomedical databases and relevant keywords. Additional references were reviewed, resulting in 18 eligible studies. Most (72%) studies were conducted in the United States and in jail settings (60%), with the main objective of improving completion rates inside the facility or after release. Studies that provided data about initiation and completion rates showed poor success in correctional facilities. Adverse consequences and treatment interruption ranged from 1% to 55% (median 5%) in reported studies; hepatotoxicity was the most prevalent adverse reaction. Despite its accelerating effect on the development of active TB, information on human immunodeficiency virus (HIV) status was provided in only half of the studies. Among the four studies where IPT effectiveness was assessed, the results mirror those described in community settings. Future studies require thorough assessments of IPT initiation and completion rates and adverse effects, particularly in low- and middle-income countries and where comorbid viral hepatitis may contribute significantly to outcomes, and in settings where TB and HIV are more endemic.

Matched MeSH terms: Isoniazid/therapeutic use*

An apparently healthy young man with a peculiar-looking chest radiograph

Khajotia R, Manthari K

Can Fam Physician, 2011 Mar;57(3):311-3.

PMID: 21402968

Matched MeSH terms: Isoniazid/therapeutic use

Fulltext Contralateral pleural effusion during chemotherapy for tuberculous pleural effusion

Puri MM, Arora VK

Med J Malaysia, 2000 Sep;55(3):382-4.

PMID: 11200723

A 25 year old woman developed a right pleural effusion 6 weeks after commencement of short course chemotherapy for left sided tuberculous pleural effusion. Since the patient improved following continuation of the same treatment, it is presumed to be a case of paradoxical response to anti-tuberculosis treatment.

Matched MeSH terms: Isoniazid/therapeutic use

Review of tuberculosis among the Orang Asli (Aborigines) in West Malaysia from 1951-1970

Bolton JM, Snelling MR

Med J Malaysia, 1975 Sep;30(1):10-29.

PMID: 813093

Matched MeSH terms: Isoniazid/therapeutic use

Isoniazid-induced encephalopathy in an end-stage renal disease patient - A case report and literature review

Low JM, Wong KW

Med J Malaysia, 2019 12;74(6):553-554.

PMID: 31929489

Patients with end stage renal disease have higher risk of tuberculosis due to lower cell-mediated immunity. Standard regime of anti-tuberculosis contains isoniazid where neurological side effects such as seizure and encephalopathy have been documented. We present a case of isoniazid-induced encephalopathy in a haemodialysis patient. A literature review on isoniazid-induced encephalopathy was done. Recognition of this condition is important as it is reversible with cessation of isoniazid and institution of high dose pyridoxine.

Matched MeSH terms: Isoniazid/therapeutic use

Fulltext Antimycobacterial susceptibility evaluation of rifampicin and isoniazid benz-hydrazone in biodegradable polymeric nanoparticles against Mycobacterium tuberculosis H37Rv strain

Hakkimane SS, Shenoy VP, Gaonkar SL, Bairy I, Guru BR

Int J Nanomedicine, 2018;13:4303-4318.

PMID: 30087562 DOI: 10.2147/IJN.S163925

INTRODUCTION: Tuberculosis (TB) is the single largest infectious disease which requires a prolonged treatment regime with multiple drugs. The present treatment for TB includes frequent administration of a combination of four drugs for a duration of 6 months. This leads to patient's noncompliance, in addition to developing drug-resistant strains which makes treatment more difficult. The formulation of drugs with biodegradable polymeric nanoparticles (NPs) promises to overcome this problem.

MATERIALS AND METHODS: In this study, we focus on two important drugs used for TB treatment - rifampicin (RIF) and isoniazid (INH) - and report a detailed study of RIF-loaded poly lactic-co-glycolic acid (PLGA) NPs and INH modified as INH benz-hydrazone (IH2) which gives the same therapeutic effect as INH but is more stable and enhances the drug loading in PLGA NPs by 15-fold compared to INH. The optimized formulation was characterized using particle size analyzer, scanning electron microscopy and transmission electron microscopy. The drug release from NPs and stability of drug were tested in different pH conditions.

RESULTS: It was found that RIF and IH2 loaded in NPs release in a slow and sustained manner over a period of 1 month and they are more stable in NPs formulation compared to the free form. RIF- and IH2-loaded NPs were tested for antimicrobial susceptibility against Mycobacterium tuberculosis H37Rv strain. RIF loaded in PLGA NPs consistently inhibited the growth at 70% of the minimum inhibitory concentration (MIC) of pure RIF (MIC level 1 µg/mL), and pure IH2 and IH2-loaded NPs showed inhibition at MIC equivalent to the MIC of INH (0.1 µg/mL).

CONCLUSION: These results show that NP formulations will improve the efficacy of drug delivery for TB treatment.

Matched MeSH terms: Isoniazid/therapeutic use

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