Influence of pH on the Effect of Hexamethylenetetramine on the Growth of Ehrlich Ascites Tumors

Abstract

Inhibition of the growth of Ehrlich tumors by i. p. injection of hexamine increased as the pH of the solution was decreased from 7.4 to 6. Survival of the mice was correspondingly prolonged. Median survivals were 16.5, 23, and 25 days for mice given 5 daily injections of 50 ml/kg body weight of 0.8 m hexamine in 0.3 m glucose at pHs of 7.4, 6.4, and 6.0, respectively, beginning the day after tumor inoculation. Median survivals were 16.5 and 28.5 days after a single injection of 400 ml/kg of 0.06 _M hexamine at pHs of 7 and 5, respectively, while similar solutions at pHs 7 and 5 without hexamine gave medians of 15.5 and 21.5 days, respectively. In vitro at pH 6.4 and 37°C some ascites cells survived in 0.8 m hexamine for 40 min, but none for 65 min; survival was measured by ability to produce tumors. Glucose had an additional small deleterious effect.

Methenamine's journey of 160 years: Repurposal of an old urinary antiseptic for treatment and hypoxic radiosensitization of cancers and glioblastoma

“…4 Methenamine concentrations in blood serum could be obtained up to 14 mmol/L in dogs and 300 μmol/L in humans. 5 In a Swedish study, it was revealed that 1 g of methenamine hippurate twice a day for 2 years prevented recurrent urinary infections by 73%, while another trial demonstrated that 2 g/d of methenamine mandelate combined with 2 g/d of ascorbic acid for 3 months decreased recurrent lower urinary infections by 56%. 4 Adverse reactions occur in less than 4% of patients treated with methenamine hippurate; the majority include gastrointestinal disturbances such as nausea, vomiting, dyspepsia, and diarrhoea, which are generally mild.…”

“…The half‐life of methenamine elimination from serum is 3–4 hours in patients with normal renal function . Methenamine concentrations in blood serum could be obtained up to 14 mmol/L in dogs and 300 μmol/L in humans . In a Swedish study, it was revealed that 1 g of methenamine hippurate twice a day for 2 years prevented recurrent urinary infections by 73%, while another trial demonstrated that 2 g/d of methenamine mandelate combined with 2 g/d of ascorbic acid for 3 months decreased recurrent lower urinary infections by 56% …”

“…For humans, orally tolerable doses are between 10 and 20 g/d, e.g. Crowe employed 90–140 mmol/L/d without major toxicity . In rabbits, 70 mmol/L/kg per os was not fatal, yet i.v.…”

“…In rabbits, 70 mmol/L/kg per os was not fatal, yet i.v. injection was not tolerable; a dose of 70 nmol/L/kg/d injected in fractions was fatal to rabbits . Haematuria is suggested as a toxicity indicator in humans, which likely occurs due to enhanced bladder wall irritation caused by higher concentrations of formaldehyde accumulating within the bladder.…”

“…Crowe employed 90-140 mmol/L/d without major toxicity. 5 In rabbits, 70 mmol/L/kg per os was not fatal, yet i.v. injection was not tolerable; a dose of 70 nmol/L/kg/d injected in fractions was fatal to rabbits.…”