Potential use of simple manganese salts as antioxidant drugs in horses

Raj K. Singh From the Hillenbrand Biomedical Engineering Center, Departments of Veterinary Physiology and Pharmacology (Singh, Babbs, Salaris, Pham) and Veterinary Clinical Sciences (Kooreman, Fessler), Purdue University, West Lafayette, IN 47907.

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 DVM, MS
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Karin M. Kooreman From the Hillenbrand Biomedical Engineering Center, Departments of Veterinary Physiology and Pharmacology (Singh, Babbs, Salaris, Pham) and Veterinary Clinical Sciences (Kooreman, Fessler), Purdue University, West Lafayette, IN 47907.

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Charles F. Babbs From the Hillenbrand Biomedical Engineering Center, Departments of Veterinary Physiology and Pharmacology (Singh, Babbs, Salaris, Pham) and Veterinary Clinical Sciences (Kooreman, Fessler), Purdue University, West Lafayette, IN 47907.

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John F. Fessler From the Hillenbrand Biomedical Engineering Center, Departments of Veterinary Physiology and Pharmacology (Singh, Babbs, Salaris, Pham) and Veterinary Clinical Sciences (Kooreman, Fessler), Purdue University, West Lafayette, IN 47907.

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Steven C. Salaris From the Hillenbrand Biomedical Engineering Center, Departments of Veterinary Physiology and Pharmacology (Singh, Babbs, Salaris, Pham) and Veterinary Clinical Sciences (Kooreman, Fessler), Purdue University, West Lafayette, IN 47907.

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JoAnn Pham From the Hillenbrand Biomedical Engineering Center, Departments of Veterinary Physiology and Pharmacology (Singh, Babbs, Salaris, Pham) and Veterinary Clinical Sciences (Kooreman, Fessler), Purdue University, West Lafayette, IN 47907.

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 Pharm D

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SUMMARY

The scavenging of superoxide radicals by endogenous and therapeutically administered superoxide dismutases may prevent superoxide-mediated oxidative stress leading to lipid peroxidation, membrane lysis, and cell death in a wide variety of normal and pathologic states. Simple inorganic manganous salts such as MnCl2 also have superoxide dismutase-like activity and are extremely inexpensive, compared with enzymatic superoxide dismutase preparations. In this study, we explored the use of Mn salts as antioxidant drugs. We used the percentage of inhibition of nitroblue tetrazolium reduction by superoxide as a measure of the amount of superoxide dismutase-like activity. We found concentration-related increases in superoxide scavenging activity in simple buffer solutions upon addition of 1.25, 2.5, and 5.0 μM MnSO4. To determine whether Mn salts can inhibit oxidative damage in tissues, we used an in vitro model of lipid peroxidation in ischemic and reoxygenated rat liver slices. Concentrations of 10, 100, and 1000 μmoles MnCl2/L of buffer significantly decreased indicators of lipid peroxidation believed to be initiated by intracellular superoxide. We then determined the effectiveness of MnCl2 as a superoxide scavenger in conscious horses by measuring the superoxide scavenging ability of equine plasma before and during intravenous infusions of 1.0 L volumes of 0.9% slaine solution containing 0, 12.5, or 25 mM MnCl2. Plasma Mn concentrations, which were determined by atomic absorption spectrophotometry, increased as a function of time and dose. Intravenously administered MnCl2 concomitantly produced dose-related increases in superoxide scavenging ability of equine plasma at 15, 30, 45, and 60 minutes after the onset of infusion, compared with preinfusion control values. Heart rate and blood pressure of the treated horses, which were monitored to measure toxicity of MnCl2, gradually increased in both treatment groups. Clinical adverse effects of MnCl2 administration included defecation, pawing, hyperexcitability, flank watching, and sweating. The results of this study indicate that simple Mn salts may scavenge superoxide radicals in vivo with minimal adverse reactions and at a trivial cost.

SUMMARY

The scavenging of superoxide radicals by endogenous and therapeutically administered superoxide dismutases may prevent superoxide-mediated oxidative stress leading to lipid peroxidation, membrane lysis, and cell death in a wide variety of normal and pathologic states. Simple inorganic manganous salts such as MnCl2 also have superoxide dismutase-like activity and are extremely inexpensive, compared with enzymatic superoxide dismutase preparations. In this study, we explored the use of Mn salts as antioxidant drugs. We used the percentage of inhibition of nitroblue tetrazolium reduction by superoxide as a measure of the amount of superoxide dismutase-like activity. We found concentration-related increases in superoxide scavenging activity in simple buffer solutions upon addition of 1.25, 2.5, and 5.0 μM MnSO4. To determine whether Mn salts can inhibit oxidative damage in tissues, we used an in vitro model of lipid peroxidation in ischemic and reoxygenated rat liver slices. Concentrations of 10, 100, and 1000 μmoles MnCl2/L of buffer significantly decreased indicators of lipid peroxidation believed to be initiated by intracellular superoxide. We then determined the effectiveness of MnCl2 as a superoxide scavenger in conscious horses by measuring the superoxide scavenging ability of equine plasma before and during intravenous infusions of 1.0 L volumes of 0.9% slaine solution containing 0, 12.5, or 25 mM MnCl2. Plasma Mn concentrations, which were determined by atomic absorption spectrophotometry, increased as a function of time and dose. Intravenously administered MnCl2 concomitantly produced dose-related increases in superoxide scavenging ability of equine plasma at 15, 30, 45, and 60 minutes after the onset of infusion, compared with preinfusion control values. Heart rate and blood pressure of the treated horses, which were monitored to measure toxicity of MnCl2, gradually increased in both treatment groups. Clinical adverse effects of MnCl2 administration included defecation, pawing, hyperexcitability, flank watching, and sweating. The results of this study indicate that simple Mn salts may scavenge superoxide radicals in vivo with minimal adverse reactions and at a trivial cost.

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