Garnett McKeen Laboratory Inc.

Shirley, NY, United States

Garnett McKeen Laboratory Inc.

Shirley, NY, United States
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Sridharan V.,University of Arkansas for Medical Sciences | Seawright J.W.,University of Arkansas for Medical Sciences | Antonawich F.J.,Garnett McKeen Laboratory Inc. | Antonawich F.J.,St. Joseph's College | And 4 more authors.
Radiation Research | Year: 2017

Exposure of the heart to ionizing radiation can cause adverse myocardial remodeling. In small animal models, local heart irradiation causes persistent alterations in cardiac mitochondrial function and swelling. POLY-MVA is a dietary supplement that contains a palladium lipoic acid complex that targets mitochondrial complex I and has been demonstrated to have greater redox potential than lipoic acid alone. POLY-MVA improves mitochondrial function and anti-oxidant enzyme activity in the aged rat heart. In this study, we tested whether POLY-MVA can mitigate cardiac effects of ionizing radiation. Adult male rats were exposed to local heart X rays with a daily dose of 9 Gy for 5 consecutive days. Eighteen weeks after irradiation, POLY-MVA was administered orally at 1 ml/kg bodyweight per day during weekdays, for 6 weeks. Alterations in cardiac function as measured with echocardiography coincided with enhanced mitochondrial swelling, a reduction in mitochondrial expression of complex II, manifestations of adverse remodeling such as a reduction in myocardial microvessel density and an increase in collagen deposition and mast cell numbers. POLY-MVA enhanced left ventricular expression of superoxide dismutase 2, but only in sham-irradiated animals. In irradiated animals, POLY-MVA caused a reduction in markers of inflammatory infiltration, CD2 and CD68. Moreover, POLY-MVA mitigated the effects of radiation on mitochondria. Nonetheless, POLY-MVA did not mitigate adverse cardiac remodeling, suggesting that this tissue remodeling may not be alleviated by altering cardiac mitochondria alone. However, we cannot exclude the possibility that an earlier onset of POLY-MVA administration may have more profound effects on radiation-induced cardiac remodeling. © 2017 by Radiation Research Society.

Krishnan C.V.,Garnett McKeen Laboratory Inc. | Krishnan C.V.,State University of New York at Stony Brook | Garnett M.,Garnett McKeen Laboratory Inc.
International Journal of Electrochemical Science | Year: 2011

We have investigated the complex cyclic voltammetric behaviour of the sodium salt of α-lipoic acid in the absence and presence of the background electrolytes, sodium chloride and phosphate buffer. Absorption data indicated deviations from Beer's law above 10 mM suggesting strong solute-solute interactions at higher concentrations. By scanning in a wide range of potentials, +2.0 to -2.0V, and using 1 mM α-lipoic acid (sodium salt), it was possible to identify the irreversible formation of thiolsulfonate, reversible formation lipoic acid S-oxide, reversible formation of dihydrolipoic acid, and reversible formation of dimers of lipoic acid. The oxidation of dihydrolipoic acid and the dimers of lipoic acid were influenced by the concentration of lipoic acid as well as the scan rate. Evidence is presented for the formation of S-oxides of lipoic acid dimers or higher polymers that are different from lipoic acid S-oxide. In the active region, the cathodic current produced depended on the concentration of α-lipoic acid. The reduction of α-lipoic acid to dihydrolipoic acid was unaffected by the starting anodic potential. The oxidation of dihydrolipoic acid was complicated by the formation of polymers of lipoic acid. With increasing concentrations of lipoic acid, the rate of increase in cathodic current due to reduction of lipoic acid was much higher than that of the reduction of lipoic acid S-oxide. Cathodic current oscillations were observed in the presence of counter ions and 10 mM α-lipoic acid. Higher pH produced less reduction currents of α-lipoic acid. Both the phosphate buffer and sodium chloride produced anodic shifts in the reduction peak of α-lipoic acid. Phosphate buffer gave a higher anodic shift in the reduction peak than sodium chloride. The cathodic peak current was higher with increasing concentrations of sodium chloride. It was possible to restrict the interference from different species on some redox processes, such as the redox process of lipoic acid S-oxide formation and reversible oxidation of dihydrolipoic acid, by restricting the range of the scanning potential and the concentration of lipoic acid. These cyclic voltammetry data suggested the need to investigate the electrochemical behaviour of molecules without any background electrolytes, whenever possible, to gain information on interactions near the double layer. This is contrary to the accepted practice in electrochemistry. Finally caution is suggested in deciding the oral dosage of lipoic acid supplements because of its tendency to polymerize under reducing biological conditions. © 2011 by ESG.

Sudheesh N.P..,Amala Cancer Research Center | Ajith T.A.,Amala Institute of Medical science | Janardhanan K.K.,Amala Cancer Research Center | Krishnan C.V.,Garnett McKeen Laboratory Inc | Krishnan C.V.,State University of New York at Stony Brook
Food and Chemical Toxicology | Year: 2010

Palladium α-lipoic acid formulation - 'POLY-MVA' is found to enhance the activities of Krebs cycle dehydrogenases and respiratory complexes in the heart of aged rat. In this study, we aimed to evaluate the effect of POLY-MVA on the activities of antioxidant status in the heart mitochondria of aged rat. We determined the activities of manganese-superoxide dismutase (Mn SOD), catalase (CAT), glutathione peroxidase (GPx), and level of reduced GSH and lipid peroxidation in the heart mitochondria of aged rats, after administering POLY-MVA (0.05. ml/kg; equivalent to 0.38. mg complexed α-lipoic acid/kg) orally once daily for 30. days. DL-α-lipoic acid (0.38. mg/kg, p.o) treated for 30. days was kept as the positive control. We found that the antioxidant in the aged control was declined significantly than the young control. The formulation significantly (p<0.05) enhanced the activity of CAT and GPx compared to the aged control. The level of GSH was also significantly improved and the level of lipid peroxidation was decreased significantly (p<0.05) by POLY-MVA. The results indicate that POLY-MVA is effective to protect the age-linked decline of myocardial mitochondrial antioxidant status. The findings suggest the use of this formulation against myocardial aging. © 2010 Elsevier Ltd.

Ramachandran L.,Amala Cancer Research Center | Krishnan C.V.,Garnett McKeen Laboratory Inc | Krishnan C.V.,State University of New York at Stony Brook | Nair C.K.K.,Amala Cancer Research Center
Cancer Biotherapy and Radiopharmaceuticals | Year: 2010

The dietary supplement, POLY-MVA, containing palladium α-lipoic acid complex was examined for its efficacy as a radioprotector in mice exposed to whole-body γ-radiation. Oral administration of POLY-MVA enhanced endogenous spleen colony formation in animals exposed to a sublethal dose of 6 Gy γ-radiation. Alkaline comet assay revealed that the nuclear DNA comet parameters such as percent DNA in tail, tail length, tail moment, and olive tail moment, of the bone marrow cells and spleen cells, were found increased following whole-body γ-irradiation. The radiation-induced DNA damage in these cells was reduced when POLY-MVA was administered to animals exposed to a lethal dose of 8 Gy whole-body γ-radiation. The administration of POLY-MVA significantly reduced the γ-radiation-induced mortality and also aided recovery from the radiation-induced loss of body weight in mice surviving after 8 Gy γ-radiation exposure. These results suggest the potential use of POLY-MVA as a radioprotector in cases of planned radiation exposures. © 2010, Mary Ann Liebert, Inc.

Veena R.K.,Amala Cancer Research Center | Ajith T.A.,Amala Institute of Medical science | Janardhanan K.K.,Amala Cancer Research Center | Antonawich F.,St. Joseph's College | Antonawich F.,Garnett McKeen Laboratory Inc.
Journal of Experimental Therapeutics and Oncology | Year: 2015

Chemopreventive agents which exhibit activities such as anti-inflammation, inhibition of carcinogen induced mutagenesis and scavenging of free radical might play a decisive role in the inhibition of chemical carcinogenesis either at the initiation or promotion stage. Many synthesized palladium (Pd) complexes tested experimentally for antitumor activity are found effective. Poly-MVA is a liquid blend preparation containing B complex vitamins, ruthenium with Pd complexed with alpha lipoic acid as the major ingredients. The antitumor effect of Poly-MVA was evaluated against 7,12-dimethylbenz[a] anthracene-initiated croton oil-promoted papilloma formation on mice skin. Skin tumor was initiated with a single application of 390 nmol of DMBA in 20 μl acetone. The effect of Poly-MVA against croton oil- induced inflammation and lipid peroxidation on the mice skin was also evaluated. Topical application of Poly-MVA (100 μl, twice weekly for 18 weeks) 30 minutes prior to each croton oil application, significantly decreased the tumor incidence (11%) and the average number of tumor per animals. Application of Poly-MVA (100 μl) before croton oil significantly (p < 0.05) protected the mouse skin from inflammation (36%) and lipid peroxidation (14%) when compared to the croton oil alone treated group. Experimental results indicate that Poly-MVA attenuate the tumor promoting effects of croton oil and the effect may probably be due to its anti-inflammatory and antioxidant activity. © 2015 Old City Publishing, Inc.

Ajith T.A.,Amala Institute of Medical science | Nima N.,Amala Cancer Research Center | Veena R.K.,Amala Cancer Research Center | Janardhanan K.K.,Amala Cancer Research Center | Antonawich F.,Garnett McKeen Laboratory Inc
Alternative Therapies in Health and Medicine | Year: 2014

Context • According to the mitochondrial mutation theory of aging, the impairment of mitochondrial functions and decline of cellular bioenergetics are induced by highly reactive oxygen species (ROS). Supplementation with antioxidants may protect mitochondria against respiration-linked oxidative stress and reduce decay by preserving genomic and structural integrity. Several clinical studies have reported beneficial effects of α-lipoic acid (LA) administration in individuals with Alzheimer’s disease, particularly improving their spatial orientation; however, no studies have been reported on the effects of palladium α-lipoic acid (Pd-LA). Objective • The current study examined the effects of the Pd-LA complex on mitochondrial energy status in the brains of aged rats. Design • The study used male Wistar rats, some that were older than 24 mo and weighed approximately 350 ± 50 g and some that were younger than 24 mo and weighed approximately 175 ± 25 g. The research team divided the rats into 5 groups of 6 rats. Setting • The study was conducted at the Amala Cancer Research Centre in Amala Nagar, Thrissur, Kerala, India. Intervention • Three groups of rats were controls: (1) young controls administered no solution, (2) aged controls administered 1 mL/kg of a 0.25% solution (PO) of sodium hydroxide (NaOH), and (3) positive aged controls treated with LA (7.6 mg/kg, PO) dissolved in an alkaline saline (0.25% NaOH, w/v). Two groups were intervention groups: (1) aged rats treated with 1.2 mg/kg of Pd-LA (PO) and (2) aged rats treated with 23.5 mg/kg of Pd-LA (PO). The research team administered the solutions once daily for 30 d. After 30 d, all animals were sacrificed. Outcome Measures • The research team evaluated serum transaminases, lactate dehydrogenase (LDH), serum urea, and creatinine. The activities of superoxide dismutase (SOD), catalase (CAT), and the levels of reduced glutathione (GSH) were determined in the blood samples. Krebs cycle dehydrogenases were evaluated in the brain mitochondria. Furthermore, the activities of the respiratory chain complexes I, III and IV as well as adenosine triphosphate (ATP) levels were estimated in the mitochondrial fraction. Results • The study found that Pd-LA elevated the mitochondrial ATP levels in the brains of aged rats by enhancing the activity of not only the Krebs cycle dehydrogenases but also complexes I and IV. Furthermore, Pd-LA improved the body weight and blood antioxidant status of aged rats without affecting the functions of liver or renal cells. Conclusions • The results of the current study demonstrate that Pd-LA improves mitochondrial energy status in the brains of aged rats. The effects can be attributed to the enhancing effect on the Krebs cycle dehydrogenase and the activities of complexes I, III, and IV. The results further support the possible use of Pd-LA as an adjuvant treatment, together with the standard cholinesterase inhibitors, in individuals with mild or moderate dementia caused by Alzheimer’s disease (AD). © 2014, InnoVision Communications. All rights reserved.

Garnett McKeen Laboratory Inc. | Date: 2013-07-18

Active chemical ingredients for use in the manufacture of pharmaceuticals for treating inflamation.


Garnett McKeen Laboratory Inc. | Date: 2013-07-18

Dietary and nutritional supplements.

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