Abstract
Subacute toxicity of pyridostigmine bromide (PB) and potassium iodate (PI) tablets upon forty five days administration were assessed by changes in body weight, hematology, serum biochemical parameters and histopathology of rat liver and kidney. LD50 of PB was estimated to be 66.9 mg/kg. At dose of 45 mg/kg/day showed decrease in body weight and liver weight with cytoplasmic acidophilic bodies and vesicular steatosis signifying hepatocellular injury. Kidney tissue developed neutrophil polymorph infiltration with inflammatory glomerulonephritis, protein casts and glomerulosclerosis. Serum SGOT, SGPT, ALP and lipid profile were elevated. The oral LD50 of PI was found to be 944.6 mg/kg. PI at 150 mg/kg dose showed anorexia and body weight loss. Serum SGOT, ALP, cholesterol and triglyceride level were elevated at 85 and 150 mg/kg dose and focal area of tubular injury and inflammatory cell infiltration occurred only at 150 mg/kg dose in kidney. The content of PB and PI has been found stable in accelerated (40 ± 2°C/75 ± 5% RH), intermediate (30 ± 2°C/65 ± 5% RH) and long term (30 ± 2°C/65 ± 5% RH) conditions. PB 30 mg/kg/day and PI 85 mg/kg/day doses are safe for rats, which are far in excess of human exposure levels.
Highlights
The research proposal aimed at validation of subacute toxicity and stability of pyridostigmine bromide (PB, 30 mg) and potassium iodate (PI, 85 mg) tablets
Body weight and relative organ weight: Pretreatment body weight of all the animals were noted and percent increases in body weight compared to initial weight were calculated
This study shows that PB above 40 mg/kg is toxic in concern to hematology, serum biochemical parameters and physiology of liver and kidney when administered for over one month continuously
Summary
The research proposal aimed at validation of subacute toxicity and stability of pyridostigmine bromide (PB, 30 mg) and potassium iodate (PI, 85 mg) tablets. Pyridostigmine belongs to a family of carbamate compounds, is a reversible acetylcholinesterase (AchE) inhibitor. Nerve agents are lethally toxic compounds as they produce an irreversible inhibition of both AchE and pseudo-AchE enzyme which are responsible for metabolic degradation of acetylcholine. Preservation acetylcholine in nerve ending induce generalized muscarinic cholinergic response e.g. fall in blood pressure and heart rate, mental confusion and ataxia, vomiting and intestinal cramps, bronchoconstriction and excessive secretion, and respiratory paralysis and death. Pyridostigmine is a quaternary carbamate inhibitor of cholinesterase that does not cross blood brain barrier and is taken daily in anticipation of an attack, which carbamylates about 30% of peripheral cholinesterase. The carbamylated enzyme eventually regenerates by natural hydrolysis and an excess Ach level reverts to normal [1]. The median lethal oral dose for PB in literature is reported to be variable as 61.6 mg/kg and 80 mg/ kg [2,3,4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
