Therapeutic profile of T11TS vs. T11TS+MiADMSA: a hunt for a more effective therapeutic regimen for arsenic exposure.

Abstract

Arsenic exposure is a serious health hazard worldwide. We have previously established that it may result in immune suppression by upregulating Th2 cytokines while downregulating Th1 cytokines and causing lymphocytic death. Treatment modalities for arsenic poisoning have mainly been restricted to the use of chelating agents in the past. Only recently have combination therapies using a chelating agent in conjunction with other compounds such as anti-oxidants, micronutrients and various plant products, been introduced. In the present study, we used T11TS, a novel immune potentiating glycopeptide alone and in combination with the sulfhydryl-containing chelator, mono-iso-amyl-dimarcaptosuccinic acid (MiADMSA) as a therapeutic regimen to combat arsenic toxicity in a mouse model. Results indicated that Th1 cytokines such as TNF-α, IFNγ, IL12 and the Th2 cytokines such as IL4, IL6, IL10 which were respectively downregulated and upregulated following arsenic induction were more efficiently restored to their near normal levels by T11TS alone in comparison with the combined regimen. Similar results were obtained with the apoptotic proteins studied, FasL, BAX, BCL2 and the caspases 3, 8 and 9, where again T11TS proved more potent than in combination with MiADMSA in preventing lymphocyte death. The results thus indicate that T11TS alone is more efficient in immune re-establishment after arsenic exposureas compared to combination therapy with T11TS+MiADMSA.

• Authors: Suhnrita Chaudhuri, Sagar Acharya, Sirshendu Chatterjee, Pankaj Kumar, Manoj Kumar Singh, Debanjan Bhattacharya, Anjan Kumar Basu, Shyamal Dasgupta, S J S Flora, Swapna Chaudhuri
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 13 Issue 6 Pg. 2943-8 ( 2012) ISSN: 2476-762X [Electronic] Thailand
• PMID: 22938487 (Publication Type: Journal Article)

Chemical References

• CD2 Antigens
• Chelating Agents
• Cytokines
• monoisoamyl-2,3-dimercaptosuccinate
• Succimer
• Arsenic

Topics

• Animals
• Apoptosis (drug effects)
• Arsenic (toxicity)
• Arsenic Poisoning (drug therapy)
• CD2 Antigens (pharmacology, therapeutic use)
• Cell Transformation, Neoplastic
• Chelating Agents (therapeutic use)
• Chelation Therapy (methods)
• Cytokines (metabolism)
• Drug Therapy, Combination
• Environmental Exposure
• Lymphocytes (drug effects)
• Mice
• Oxidative Stress (drug effects)
• Succimer (analogs & derivatives, pharmacology, therapeutic use)