piperidines and Kidney-Tubular-Necrosis--Acute

We test the hypothesis that PARP inhibition can decrease acute tubular necrosis (ATN) and other renal lesions related to prolonged cold ischemia/reperfusion (IR) in kidneys preserved at 4°C in University of Wisconsin (UW) solution. Material and Methods. We used 30 male Parp1(+/+) wild-type and 15 male Parp1(0/0) knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone (DPQ) at a concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h in UW solution plus DPQ). We processed samples for morphological, immunohistochemical, ultrastructural, and western-blotting studies. Results. Prolonged cold ischemia time in UW solution increased PARP-1 expression and kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation in UW solution decreased PARP-1 nuclear expression in renal tubules and renal damage. Parp1(0/0) knockout mice were more resistant to IR-induced renal lesion. In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these data suggest that pharmacological manipulation of PARP activity may have salutary effects in cold-stored organs at transplantation.

Topics: Animals; Blotting, Western; Cold Temperature; Ischemia; Isoquinolines; Kidney; Kidney Tubular Necrosis, Acute; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Electron; Piperidines; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Reperfusion Injury

We report the clinical and histological findings in patients with acute renal failure caused by the ingestion of wildfowl who had eaten hemlock buds. Neurotoxic effects were accompanied by rhabdomyolysis, myoglobinuria, and acute tubular necrosis. Histological studies showed diffuse degeneration of the tubular epithelium. Immunohistological studies demonstrated the presence of myoglobin and actin in renal tubular cells.

Topics: Acute Kidney Injury; Alkaloids; Animals; Birds; Humans; Kidney; Kidney Tubular Necrosis, Acute; Piperidines; Plant Poisoning

In the past, hemlock poisoning was only known for its neurotoxic effects; quite recently non-neurological features, consisting of rhabdomyolysis and acute renal failure, have been also described. Here we report our experience with these clinical findings, which we frequently observe in accidental hemlock poisoning. Between 1972 and 1990 we studied 18 patients: 17 of them were poisoned by conline (an alkaloid of Conium maculatim) in Apulia (Italy), and one by cicutoxin (the active principle of water hemlock) in New Mexico (USA). In the non-rapidly-fatal cases we tested myoglobinuria, serum muscle enzymes, and renal function. In the patients with acute renal failure we performed microscopical examination of kidney specimens; immunohistochemistry was carried out to identify myoglobin and actin in tubules. Coniine was detected in urine, serum, or tissues. Neurological features were present in all of our cases: coniine had a curare-like effect on the neuromuscular junction, whereas cicutoxin was convulsant on the central nervous system. In addition rhabdomyolysis was noted in the 17 subjects poisoned by coniine. Acute renal failure was observed in five patients; it was confirmed by histological evidence of tubular necrosis with intratubular deposition of myoglobin and actin released by rhabdomyolysis. Our cases seem to be the first with histopathologically proven acute tubular necrosis in coniine intoxication. In conclusion, in hemlock poisoning neurotoxic manifestations may be accompanied by rhabdomyolysis and acute tubular necrosis; increased awareness of these clinical features is recommended in order to improve the diagnostic and therapeutic procedure.

Topics: Adult; Aged; Alkaloids; Alkynes; Diynes; Fatty Alcohols; Female; Humans; Kidney Tubular Necrosis, Acute; Male; Middle Aged; Nervous System Diseases; Piperidines; Plant Poisoning; Rhabdomyolysis

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Alkaloids; Analgesics; Animals; Birds; Female; Humans; Kidney Tubular Necrosis, Acute; Male; Middle Aged; Piperidines; Rhabdomyolysis; Seasons