SEA BUCKTHORN (H. RHAMNOIDES L.) MEDIATED ACUTE HYPOXIC TOLERANCE IN THE SKELETAL MUSCLE OF RATS BY DIFFERENTIAL ACTIVATION OF ENERGY METABOLISM AND ENHANCED ANTIOXIDANTS

Exposure to hypobaric hypoxia differentially affects physical performance and survival amongst individuals. The present study was designed to investigate the role of metabolic enzymes, antioxidants and bioenergetics molecular markers in the differential hypoxic tolerance of animals exposed to acute hypobaric hypoxia and the effect of herbal supplementation in augmentation of hypoxia tolerance. Adult rats were categorized as susceptible (<10 min), normal (10-25 min) and tolerant (>25min) on the basis of time taken for onset of gasping when exposed to a simulated altitude of 9754 m (~205 mm Hg). Animals susceptible to hypoxic stress showed significantly higher levels of reactive oxygen species and malondialdehyde, concomitant with lower endogenous antioxidants viz. superoxide dismutase (SOD) and catalase (CAT) levels. These groups of animals also showed increased lactate dehydrogenase activity. Conversely, tolerant animals displayed enhanced antioxidants (SOD, CAT and GSH), citrate synthase (CS) and glucose-6-phosphate dehydrogenase (G6PD) activities. Hypobaric hypoxia up-regulated the expression of key signaling proteins involved in energy metabolism viz. hypoxia inducible factor-1α (HIF-1α), AMP-activated protein kinase-α (AMPKα) and glucose transporter4 (GLUT4) in the tolerant group. Supplementation of Sea buckthorn (SBT) leaf aqueous lyophilized extract, distinctly improved the hypoxic gasping time in animals. This may be due to the SBT mediated increase in the CS, G6PD activity and AMPKα, GLUT4 expression in the treated group compared to hypoxia group. In conclusion, better bioenergetics and antioxidants status might be responsible for tolerance behaviour in rats under hypoxia. Further, SBT supplementation imparts tolerance to hypoxia susceptible animals by facilitating intracellular energy content and augmenting antioxidants under acute hypoxia.