Oxyphenbutazone

Carfilzomib (CFZ), a chemotherapeutic agent used for multiple myeloma treatments reported to cause high incidence of cardiac events either new onset and/or exacerbate formerly diagnosed heart failure with ventricular and myocardial dysfunction. Purpose: Current research designed to explore and examine the preventive effect of oxyphenbutazone in the CFZ -instigated cardiotoxicity. Methodology: Female Wistar Rats weighing 200-250 g selected randomly and grouped as follows: Group 1 designated as the Normal control and receive normal saline only. Group 2 served toxic control and exposed to CFZ (4 mg/kg, intraperitoneally [i.p.]). Group 3 & 4 served as treatment groups and administered with CFZ concomitantly orally fed with oxyphenbutazone at doses of 35 and 70 mg/kg/three times a week, respectively. The total duration of experimental protocol was of 21 days. After completion of the experiments animals subjected to blood collection using light ether anesthesia and serum was separated for biochemical analysis further. The serum levels of Mg⁺², Ca⁺² and cardiac enzymes (aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase-MB (CK-MB) levels were estimated. Later animals sacrificed and heart tissue isolated for further examinations. Intracellular proteins NFkB and IkBα were estimated by western blot. Results: The serum analysis revealed that CFZ administration significantly elevated the levels of LDH, CK and CKMB in CFZ exposed animals when compared to normal animals while administration of oxyphenbutazone significantly reduced these biochemical changes, Intracellular antioxidant enzymes and NF-kB in treatment groups as compared to disease control animals. Conclusion: Findings of the research protocol suggests significant injuries to cardiac tissues when animals exposed to CFZ and Oxyphenbutazone protected the cardiac tissues.

Nearly all of the American horses exported to Mexico and Canada are slaughtered for human consumption, and their meat is either exported around the world or consumed locally. Previous work showed that 18 Thoroughbred racehorses purchased by rescues that would have otherwise been sold for export for the sole purpose of slaughter to produce meat for human consumption were administered phenylbutazone. We report the number of American horses exported to Canada and Mexico from 2016 to 2021, the presence of contaminated horsemeat from Canadian slaughterhouses, and the human use and idiosyncratic effects of veterinary phenylbutazone and side effects of clenbuterol, 2 of the drugs that were found in contaminated Canadian horsemeat. The number of live American horses exported to Canada declined precipitously from 2016 to 2017, and a second decline occurred in 2020. All food-producing animals are under strict regulatory control to prevent animals administered banned drugs to enter the food chain. A major principle of this program is zero tolerance for banned drugs and testing for compliance. No regulatory process is in place to remove horses administered banned drugs such as phenylbutazone. The efficacy lasts for more than 24 hours as a result of the irreversible binding to cyclooxygenase, slow elimination, and long elimination half-life of its metabolite oxyphenbutazone. High or frequent doses of phenylbutazone result in disproportionately increased plasma concentrations, which result in the residual presence in tissues. It is this fact that underlies the ban of this drug in food-producing animals. No human clinical surveillance program is in place to monitor individuals on the possible short- and long-term consequences of banned drugs in contaminated horsemeat. If the United States is unable to put in place a regulatory program to remove horses administered banned drugs as exists for all food-producing animals, the exportation of American horses across both borders for the sole purpose of slaughter for human consumption must end.