Glutamine synthetase (GS) activity in urine as index of segment-specific injury

GS, a mitochondrial enzyme present in a variety of tissues including kidney, is responsible for the production of glutamine from glutamate. In the kidney, it is localized only in the early and late portion of the pars recta of the proximal tubule. This exclusive localization may be used to study, without invasive and difficult to achieve methods, the effects of nephrotoxicants on the straight portion of the proximal tubule. Male, two months old, Wistar rats were treated with 1.0 mg/kg b.w. i.p. of mercuric chloride (Hg2+) or 100 mg/kg b.w. i.p. of hexachloro-1:3-butadiene (HCBD), both chemical specific toxicants for the straight portion, or 25 mg/kg b.w. s.c. of potassium dichromate (Cr6+), specific toxicant for the convoluted portion. Urines were collected 14 hours before and every 10 or 14 hours until 96 hours after treatment. At the same time of urine collection, histological examination of the kidney of an ancillary group treated with the same doses was performed. The results show a peak of GS excretion 24 hours after treatment with Hg2+ or HCBD, related to focal (Hg2+) or diffuse (HCBD) necrosis of the pars recta. After the peak of excretion, enzyme activity in urine decreases progressively until the end of the observation period, but it doesn’t normalize, though regeneration of the cell of the pars recta was almost complete after 96 hours for both chemicals. On the contrary, treatment with Cr6+ doesn’t affect GS excretion in urine until 72 hours after treatment, when a slight excretion of the enzyme is related to the histological findings of a focal vacuolization of the pars recta. High excretion of the enzyme appears related to the necrosis of the straight segment, because damage without necrosis, as induced by Cr6+, causes only a slight excretion. This fact may be explained by the mitochondrial localization, organelles highly sensitive to the necrosis. In conclusion, specific injury of the proximal straight tubule may be well defined by means of urinary GS. In our opinion, segment-specific injury by nephrotoxicants may be measured by means of tubular enzymes. In addition, segment-specific origin may be defined by means of segment-specific nephrotoxicants.