Size restricted silymarin suspension evokes integrated adaptive response against acute hypoxia exposure in rat lung.
Despite its extraordinary antioxidant capacity, the clinical usage of silymarin has remained restricted to amelioration of hepatic pathology. Perhaps its low bioavailability and uneven bio-distribution, owing to its poor aqueous solubility, are two main causes that have dampened the clinical applicability and scope of this preparation. We took these two challenges and suggested an unexplored application of silymarin. Apart from liver, two of the most susceptible vital organs at the highest risk of oxidative stress are brain and lung, especially during reduced oxygen saturation (hypoxia) at anatomical level. Hypoxia causes excess generation of radicals primarily in the lungs as it is the first organ at the interphase of atmosphere and organism making it the most prone and vulnerable to oxidative stress and the first responder against hypobaric hypoxia. As our first objective, we improved the silymarin formulation by restricting its size to the lower threshold and then successfully tested the prophylactic and therapeutic action in rat lung challenged with simulated hypobaric hypoxia. After dose optimization, we observed that 50mg/kg BW silymarin as size restricted and homogenous aqueous suspension successfully minimized the reactive oxygen species and augmented the antioxidant defense by significant upregulation of catalase and superoxide dismutase and reduced glutathione. Moreover, the well-established hypoxia markers and proteins related to hypoxia adaptability, hif1a and VEGF were differentially regulated conferring significant reduction in the inflammation caused by hypobaric hypoxia. We therefore report,the unexplored potential benefits of silymarin for preventing high altitude associated pathophysiology further paving its road to clinical trials.
Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization (DRDO), Ministry of Defence, Lucknow Road, Timarpur, Delhi 110054, India.
Subhojit
S
Paul
Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization (DRDO), Ministry of Defence, Lucknow Road, Timarpur, Delhi 110054, India.
Aditya
A
Arya
Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization (DRDO), Ministry of Defence, Lucknow Road, Timarpur, Delhi 110054, India.
Anamika
A
Gangwar
Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization (DRDO), Ministry of Defence, Lucknow Road, Timarpur, Delhi 110054, India.
Kalpana
K
Bhargava
Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization (DRDO), Ministry of Defence, Lucknow Road, Timarpur, Delhi 110054, India. Electronic address: yasminchem@gmail.com.
Yasmin
Y
Ahmad
D000532:Altitude Sickness / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001682:Biological Availability; D001921:Brain / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012838:Silymarin / Q000008:administration & dosage*; D013482:Superoxide Dismutase / Q000378:metabolism; D013535:Suspensions / Q000008:administration & dosage; D014867:Water / Q000737:chemistry
D017382:Reactive Oxygen Species; D012838:Silymarin; D013535:Suspensions; D014867:Water; D002374:Catalase; D013482:Superoxide Dismutase
Antioxidant; Hypobaric hypoxia; Oxidative stress; Silymarin