ABSTRACT
Arsenic toxicity is one of the major environmental problems causing various diseases, cardiovascular disorders is one of them. Several epidemiological studies have shown that arsenic causes cardiac hypertrophy but the detailed molecular mechanism is to be studied yet. This study is designed to determine the molecules involved in the augmentation of arsenic-induced cardiac hypertrophy. Furthermore, the effects of oleic acid on arsenic-induced hypertrophy and cardiac injury have also been investigated. Our results show that arsenic induces cardiac hypertrophy both in vivo in mice and in vitro in rat H9c2 cardiomyocytes. Moreover, arsenic results in decreased activity of AMPK and FoxO1 along with increased NFATc3 expression, a known cardiac hypertrophy inducer. In addition, activation of AMPK and FoxO1 results in reduced NFATc3 expression causing attenuation of arsenic-induced cardiac hypertrophy in H9c2 cells. Interestingly, we have observed that oleic acid helps in ameliorating cardiac hypertrophy in arsenic-exposed mice. Our studies on protection from arsenic-induced cardiac hypertrophy by oleic acid in H9c2 cells shows that oleic acid activates AMPK along with increased nuclear FoxO1 localization, thereby reducing NFATc3 expression and attenuating cardiomyocyte hypertrophy. This study will help in finding out new avenues in treating arsenic-induced cardiac hypertrophy.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Cardiomegaly/prevention & control , Forkhead Box Protein O1/metabolism , Myocytes, Cardiac/drug effects , NFATC Transcription Factors/metabolism , Nerve Tissue Proteins/metabolism , Oleic Acid/pharmacology , Animals , Arsenic Trioxide , Cardiomegaly/chemically induced , Cardiomegaly/enzymology , Cardiomegaly/pathology , Cardiotoxicity , Cell Line , Disease Models, Animal , Fibrosis , Forkhead Box Protein O1/genetics , Male , Mice , Myocytes, Cardiac/enzymology , Myocytes, Cardiac/pathology , NFATC Transcription Factors/genetics , Nerve Tissue Proteins/genetics , Signal TransductionABSTRACT
AIM: Testing the potential of citrate-capped Mn3O4 nanoparticles (NPs) as a therapeutic agent for alternative rapid treatment of hyperbilirubinemia through direct removal of bilirubin (BR) from blood in mice. MATERIALS & METHODS: NPs were synthesized and the mechanism of BR degradation in presence and absence of biological macromolecules were characterized in vitro. To test the in vivo BR degradation ability of NPs, CCl4-intoxicated mice were intraperitoneally injected with NPs. RESULTS: We demonstrated ultrahigh efficacy of the NPs in symptomatic treatment of hyperbilirubinemia for rapid reduction of BR in mice compared with conventional medicine silymarin without any toxicological implications. CONCLUSION: These findings may pave the way for practical clinical use of the NPs as safe medication of hyperbilirubinemia in human subjects.
Subject(s)
Hyperbilirubinemia/drug therapy , Manganese Compounds/therapeutic use , Nanoparticles , Oxides/therapeutic use , Animals , Circular Dichroism , Hyperbilirubinemia/pathology , Mice , Surface PropertiesABSTRACT
Jaundice is one of the notable markers of liver malfunction in our body, revealing a significant rise in the concentration of an endogenous yellow pigment bilirubin. We have described a method for measuring the optical spectrum of our conjunctiva and derived pigment concentration by using diffused reflection measurement. The method uses no prior model and is expected to work across the races (skin color) encompassing a wide range of age groups. An optical fiber-based setup capable of measuring the conjunctival absorption spectrum from 400 to 800 nm is used to monitor the level of bilirubin and is calibrated with the value measured from blood serum of the same human subject. We have also developed software in the LabVIEW platform for use in online monitoring of bilirubin levels in human subjects by nonexperts. The results demonstrate that relative absorption at 460 and 600 nm has a distinct correlation with that of the bilirubin concentration measured from blood serum. Statistical analysis revealed that our proposed method is in agreement with the conventional biochemical method. The innovative noncontact, low-cost technique is expected to have importance in monitoring jaundice in developing/underdeveloped countries, where the inexpensive diagnosis of jaundice with minimally trained manpower is obligatory.
