Nullification of a positive correlation between urinary contents of α1-microglobulin and ulinastatin with intracerebroventricularly administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+) in mice

Abstract

Striatal dopamine contents in C57BL/6J mice were reduced at 24 h after intracerebroventricular (ICV) administration of 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP⁺) in a dose-dependent manner. A dose of 1.8 μg MPP⁺ significantly (P < 0.05) suppressed the dopamine contents, whereas a similar dose of MPTP did not. A definite positive correlation between urinary contents of α₁-microglobulin (α₁M) and ulinastatin (UT) existed in normal mice. However, this correlation was nullified by ICV administration of 18 and 36 μg MPTP or 1.8 and 18 μg MPP⁺. With 1.8 μg MPTP, a positive correlation between urinary contents of α₁M and UT was displayed. The urine volume, creatinine content, glomerular filtration rate, α₁M and UT contents, and α₁M/UT ratio of urine collected for 24 h post-ICV administration of MPTP or MPP⁺, were not statistically different from those of control mice. Our findings suggest that the central effects of MPP⁺, a neurotoxic metabolite of MPTP, nullify the positive correlation between urinary contents of α₁M and UT without affecting renal functions.