Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the protective effects of medical castration by means of gonadotropin-releasing hormone analogue (GnRHA) on the toxic effects of cisplatin in rats. Twelve days after a s.c. injection of a slowly-releasable form of leuprolide acetate (GnRHASR), rats were injected i.p. with cisplatin daily (3 mg/kg body weight (BW) for males and 4 mg/kg BW for females) for four days and sacrificed 24 h after the last injection. The doses caused acute tubular necrosis and gastrointestinal (GI) symptoms, i.e., diarrhea and fluid retention and bleeding in GI tract. GnRHASR pretreatment reduced serum urea nitrogen (SUN) and serum creatinine (SCre) increase and the incidence of GI symptoms. Histological analysis showed that rats pretreated with GnRHASR had noticeably less kidney damage. GnRHA thus demonstrated its ability to protect the kidneys and GI tract against cisplatin toxicity in both male and female rats. This finding suggests a potential clinical application of GnRHA in antineoplastic chemotherapy.
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PMID:Leuprolide acetate prevents toxic effects of cisplatin on the kidneys and gastrointestinal tract. 767 May 59

LHRH-PE40, a recombinant DNA-derived protein composed of LHRH and Pseudomonas aeruginosa exotoxin A, is being developed for the treatment of malignant tumours. This experiment was designed to assess its preclinical safety. Reproductive toxicity studies, pharmacokinetic studies, single- and repeat-dose intraperitoneal or intravenous toxicity studies in mice, rats and monkeys were conducted to assess the toxicity of LHRH-PE40. In intravenous single-dose studies in mice, the LD50 was 731.26 microg/kg and 676.03 microg/kg in male and female mice respectively. In single-dose studies and repeat-dose range-finding studies in rats, dose-limited severe vascular leakage syndromes occurred. In repeat-dose long-term studies, except drug-related vascular leakage syndromes, other drug-related changes included decreased testis weight and testis atrophy. In single-dose and repeat-dose studies in monkeys, dose-limited acute tubular necrosis of the kidneys was the chief finding. In reproductive studies, drug-related changes were decreased food intakes, decreased testis weight and uterus weight, decreased foetus weight and increased foetus mortality, increased maternal and F1 offspring mortality and decreased maternal and F1 offspring body weight. Pharmacokinetic studies showed a similar half-time of distribution and clearance in mice and monkeys. Tissue distribution showed a high concentration in the kidneys and a low concentration in the brain. LHRH-PE40 induced vascular leak syndromes in rats and acute tubular necrosis in monkeys. It also led to testicle atrophy in rats and overt productive toxicity to parents and F1 generations in mice. Because of these findings, it should be monitored carefully in human clinical trials for things such as respiratory, urinary and reproductive toxicities.
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PMID:A recombinant protein LHRH-PE40 for tumour therapy: preclinical safety studies. 1716 19