Abstract---Alpha Ketoglutarate (AKG), the active metabolite nutraceutical have been available in market and has been demonstrated to have anti-oxidant properties previously. Newer metabolic functioning of this novel metabolite have been under covered recently in microbial studies, indicati ng there is more to α- KG, and it might be an evolutionary molecule and a common linking metabolite which acts to help cell survive when it is exposed to various stressors. The current study assess its hepatoprotective effectiveness in a well-established CCl4 induced acute hepatotoxic animal model, which are now known to have both lipid peroxidation dependent and independent pathways causing liver injury. Parameters assessed included, Biochemical (Liver functioning tests, oxidative stress, antioxidant levels) and histopathological assessment. 99m Tc-Mebrofenin Nuclear (functional imaging) of animals were done, it provides objective validation of other parameters assessed, provides in-vivo quantification of liver functioning and parameters assessed can quantify oxidative and inflammatory pathways to liver injury and intervention response distinctly. Keywords---Alpha-Ketoglutarate (AKG), Carbon Tetrachloride (CCl4), Hepatotoxicity, 99m Technetium-Mebrofenin I. INTRODUCTION In past decade or so nutraceutical have generated great deal of consumer interest, largely on account of reported beneficial potential of these novel bioactives to treat chronic conditions with fewer to no side effect profile. Scientific research supporting the biological activities of these nutraceuticals in, in-vitro and in-vivo experimental models lack stringent validating criterion. Also inability to undercover the most active metabolite among the various polyphenols; scarce and inconclusive human trials; lack of long term studies, have led low confidence and criticism from the clinical fraternity [1]. Thus there is a need for stringent scientific validation of prophylactic and therapeutic utility of these class of agents. Alpha-ketoglutarate (AKG), non-essential amino acid, have been marketed for some time now with various reported Lalita Mehra, Amit Kumar, Aseem Bhatnagar, Gaurav Mittal, INMAS, DRDO, India. Email id: lalita.mehra@ymail.com Yasha Hasija, Delhi Technological University, India benefits, most important being its anti-ageing and anabolic properties which have been ascribed largely to its antioxidant properties. Biochemically AKG has been described for its ability to convert ammonia to non-toxic amino acids like glutamine, non-enzymatic oxidative decarboxylation of hydrogen peroxide and as such suppresses free radical generation and prevention of lipids peroxidative damage [2]. AKG is shown to inhibit oxidative stress induced by H 2 O 2 in erythrocytes and cultured neurons [3], [4]. In addition to its protective activity on redox homeostasis, AKG is shown to have chelating properties by forming, active complexes with iron in brain homogenates [5]. As such AKG is known to have anti-oxidant properties. In past AKG has been shown to be effective as an antidote against cyanide poisoning [6], reducing oxidative stress caused by sodium valproate [7], ethanol [8], and ammonium acetate [2]. More novel roles that AKG might have in a cell than merely having antioxidant properties are being under-covered. Recent mechanistic studies showed newer molecular mechanisms of this metabolite. α-KG inhibits ATP synthase and leads to reduced ATP content, decreased oxygen consumption and increased autophagy, in both C. elegans and mammalian cells and also shown to prevent mtDNA damage. Thus α-KG might be an evolutionary molecule and a common linking metabolite which acts to help cell survive when it is exposed to various stressors [9]. Carbon- tetrachloride (CCl 4 ) is a well-known potent hepatotoxin, which has been used since seventies to create in- vivo models of acute and chronic liver injuries. The critical mechanism and signaling pathways for pathogenesis in well perfused liver and isolated or cultured hepatocytes have been elucidated [10]. Now there is a growing body of evidence to suggest that CCl 4 toxicity is, rather a mutifactorial process, unlike as previously thought. Earlier, much of CCl 4 hepatotoxicty, had been attributed to its activation by mitochondrial cytochrome P450 (CYP) 2E1, and very marginally by other CYPs (CYP2B and CYP3A), resulting in formation of trichloromethyl (CCl 3 . ) and trichloromethylperoxy radical (CCl 3 OO . ). Both free radicals Assessing Nutraceutical Alpha Ketoglutarate for Its Effectiveness: 99m Technetium- Mebrofenin Nuclear Imaging in CCl 4 Induced Hepatotoxic Animal Model Lalita Mehra, Amit Kumar, Aseem Bhatnagar, Yasha Hasija, and Gaurav Mittal International Conference on Chemical, Food and Environment Engineering (ICCFEE'15) Jan. 11-12, 2015 Dubai (UAE) 66