Histological and ultrastructural changes in the rat brain following systemic administration of picolinic acid

Effects of Pre- and Postnatal Exposure to Chromium Picolinate or Picolinic Acid on Neurological Development in CD-1 Mice

“…In direct contrast to the results of Beskid et al [33], we saw no evidence of spongiosis or overt insult to the pyramidal neurons of the CA3 region of the hippocampus. The differences in observations can most likely be attributed to differences in administration and dosage.…”

“…Thus, only ∼2% of the daily dose of picolinic acid in our study was likely absorbed. In addition, hippocampal insult was observed at dosages of 60 or 100 mmol/day in the Beskid et al [33] study or approximately 7.38 or 12.31 g/day. Our study utilized a dosage of 0.007 g/day (based on an average mouse mass of 0.40 kg and a dosage of 0.174 g kg −1 day −1 ), an approximately 1,000-fold lower dosage.…”

“…Picolinic acid is a quinolinic acid partial antagonist, alleviating many of the seizures and behavioral deficits caused by intracerebral quinolinic acid administration, while not inducing any neurotoxic effects itself [50]. However, a 1995 study by Beskid et al [33] indicated that administration of high levels of exogenous picolinic acid resulted in neurological insult to pyramidal neurons in the CA3 region of the hippocampus and accompanying spongiosis. Several possible explanations were offered, including interference with zinc metabolism, interference with L-kynurenine metabolism, and non-specific toxicity.…”

“…The differences in observations can most likely be attributed to differences in administration and dosage. In the Beskid et al [33] study, the picolinic acid was administered via daily intraperitoneal injection, ensuring maximal absorption. In contrast, we administered the picolinic acid in the diet, better mimicking the normal route of human intake.…”

“…Its ability to function as a protective immunomodulator has been demonstrated in several studies involving intracerebral infection and tumor growth [31,32]. However, at high doses, picolinic acid has been suggested as being neurotoxic, inducing injury to neuronal cell bodies and spongiosis of the hippocampus [33].…”